breast cancer treatment research studies

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Breast Cancer Treatments: Updates and New Challenges

Anna burguin.

1 Department of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1T 1C2, Canada; [email protected]

2 Cancer Research Center, CHU de Québec-Université Laval, Quebec City, QC G1V 4G2, Canada; [email protected]

Caroline Diorio

3 Department of Preventive and Social Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1T 1C2, Canada

Francine Durocher

Associated data.

The study did not report any data.

Breast cancer (BC) is the most frequent cancer diagnosed in women worldwide. This heterogeneous disease can be classified into four molecular subtypes (luminal A, luminal B, HER2 and triple-negative breast cancer (TNBC)) according to the expression of the estrogen receptor (ER) and the progesterone receptor (PR), and the overexpression of the human epidermal growth factor receptor 2 (HER2). Current BC treatments target these receptors (endocrine and anti-HER2 therapies) as a personalized treatment. Along with chemotherapy and radiotherapy, these therapies can have severe adverse effects and patients can develop resistance to these agents. Moreover, TNBC do not have standardized treatments. Hence, a deeper understanding of the development of new treatments that are more specific and effective in treating each BC subgroup is key. New approaches have recently emerged such as immunotherapy, conjugated antibodies, and targeting other metabolic pathways. This review summarizes current BC treatments and explores the new treatment strategies from a personalized therapy perspective and the resulting challenges.

1. Introduction

Breast cancer (BC) is the most frequent cancer and the second cause of death by cancer in women worldwide. According to Cancer Statistics 2020, BC represents 30% of female cancers with 276,480 estimated new cases and more than 42,000 estimated deaths in 2020 [ 1 ].

Invasive BC can be divided into four principal molecular subtypes by immunohistological technique based on the expression of the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) [ 2 ]. Luminal A BC (ER+ and/or PR+, and HER2-) represents around 60% of BC and is associated with a good prognosis [ 3 ]. Luminal B BC (ER+ and/or PR+, and HER2+) represents 30% of BC and is associated with high ki67 (>14%), a proliferation marker, and a poor prognosis [ 4 ]. HER2 BC (ER-, PR-, and HER2+) represents 10% of BC and is also associated with a poor prognosis [ 5 ]. Lastly, triple-negative BC (TNBC) (ER-, PR-, and HER2-) represents 15–20% of BC and is associated with more aggressivity and worse prognosis compared to other BC molecular subtypes and often occurs in younger women [ 6 ]. Characteristics of BC by molecular subtypes are described in Figure 1 .

Characteristics of breast cancer molecular subtypes. ER: estrogen receptor; PR: progesterone receptor; HER2: human epidermal growth factor receptor 2; TNBC: triple-negative breast cancer. a . Frequency derived from Al-thoubaity et al. [ 12 ] and Hergueta-Redondo et al. [ 13 ]. b . Grade derived from Engstrom et al. [ 14 ]. c . Prognosis derived from Hennigs et al. [ 15 ] and Fragomeni et al. [ 16 ]. d . The 5–year survival rate derived from the latest survival statistics of SEER [ 7 ].

The 5-year relative BC-specific survival rate of BC is encouraging with 90.3% for all subtypes and stages. However, for metastatic BC the 5-year relative cancer-specific survival rate is still low: 29% regardless of subtype and can drop to 12% for metastatic TNBC [ 7 ]. This clearly indicates that strategies of treatment for metastatic BC patients are not effective enough to ensure a good survival rate. Thus, it is crucial to find new solutions for the treatment of metastatic BC and especially TNBC.

Treatment choice is based on the grade, stage, and BC molecular subtype to have the most personalized, safe, and efficient therapy. The grade describes the appearance of tumor cells compared to normal cells. It includes tubule differentiation, nuclear pleomorphism, and the mitotic count [ 8 ]. The stage is used to classify the extent of cancer in the body and is defined using the TNM system comprising tumor size, lymph node status, and the presence of metastases [ 9 ]. For non-metastatic BC, the strategic therapy involves removing the tumor by complete or breast-conserving surgery with preoperative (neoadjuvant) or postoperative (adjuvant) radiotherapy and systemic therapy including chemotherapy, and targeted therapy. Targeted therapy comprises endocrine therapy for hormone receptor-positive (HR+) BC and anti-HER2 therapy for HER2+ BC. Unfortunately, there is no available targeted therapy for the TNBC subtype. For metastatic BC the priority is to contain tumor spread as this type of BC remains incurable. The same systemic therapies are used to treat metastatic BC [ 10 ].

Challenges in the treatment of BC including dealing with treatment resistance and recurrence. Indeed, 30% of early-stage BC have recurrent disease, mostly metastases [ 11 ]. Thus, it is crucial to develop new strategic therapies to treat each BC subgroup effectively.

This review will summarize current treatments for invasive BC, the underlying resistance mechanisms and explore new treatment strategies focusing on personalized therapy and the resulting challenges.

2. Common Treatments for All Breast Cancer Subtypes

In addition to surgery, radiotherapy and chemotherapy are used routinely to treat all BC subtypes [ 17 ].

2.1. Surgery

The most standard breast surgery approaches are either total excision of the breast (mastectomy), usually followed by breast reconstruction, or breast-conserving surgery (lumpectomy). Lumpectomy entails the excision of the breast tumor with a margin of surrounding normal tissue. The recommended margins status is defined as “no ink on tumor”, meaning no remaining tumor cells at the tissue edge [ 18 ]. Studies show that total mastectomy and lumpectomy plus irradiation are equivalent regarding relapse-free and overall survival (OS) [ 19 ]. Contraindications for breast-conserving surgery include the presence of diffuse microcalcifications (suspicious or malignant-appearing), disease that cannot be incorporated by local excision with satisfactory cosmetic result, and ATM (ataxia-telangiesctasia mutated) mutation (biallelic inactivation) [ 18 ].

The surgery to remove axillary lymph nodes is useful to determine cancerous cell spread and for therapeutic purposes. For instance, axillary lymph node dissection (ALND) can improve survival rated by removing remaining tumor cells. ALND used to be the goal standard for removing positive lymph nodes. However, clinical trials showed that sentinel lymph node biopsy (SLNB) had the same effect as ALND regarding disease-free survival (DFS) and OS [ 20 ]. Other clinical trials demonstrated that ALND was not necessary for all patients with positive lymph nodes. Moreover, most patients who receive radiation and systemic treatment after SLNB have negative lymph nodes as these treatments are sufficient in eliminating residual tumor cells [ 21 ].

2.2. Radiotherapy

Radiation therapy has been used to treat cancer since Röngten discovered the X-ray in 1895 [ 22 ]. High-energy radiations are applied to the whole breast or a portion of the breast (after breast-conservative surgery), chest wall (after mastectomy), and regional lymph nodes [ 23 ]. A meta-analysis showed that radiation following conservative surgery offered more benefits to patients with higher-risk BC while patients with small, low-grade tumors could forego radiation therapy [ 24 ]. Postmastectomy radiation to the chest wall in patients with positive lymph nodes is associated with decreased recurrence risk and BC mortality compared to patients with negative lymph nodes [ 25 ]. A radiation boost to the regional node radiation treatment can be incorporated after mastectomy for patients at higher risk for recurrence [ 26 ]. This additional radiation boost to regional nodes following mastectomy is associated with improved (DFS) but is also associated with an increase in radiation toxicities such as pneumonitis and lymphedema [ 27 ]. Radiotherapy can be administered concurrently with personalized therapy (anti-HER2 therapy or endocrine therapy).

As one of the major side effects of radiotherapy is cardiotoxicity, it is critical to minimize exposure to the heart and lungs [ 28 ]. Additional techniques can be used to reduce the radiation exposure to the heart, lungs, and normal tissue such as prone positioning, respiratory control, or intensity-modulated radiotherapy [ 29 ].

Advanced invasive BC can exhibit radiation therapy resistance [ 30 ]. The hypoxic tumor microenvironment, which lacks oxygen, leads to increased cell proliferation, apoptosis resistance, and radiotherapy resistance [ 31 ]. The major player of this resistance is the HIF-1α (hypoxia-inducible factor 1 alpha) protein [ 32 ]. Indeed, HIF-1α overexpression is caused by low oxygen levels within the microenvironment and promotes the maintenance of hypoxia by allowing tumoral cells to survive in a hypoxic microenvironment [ 33 , 34 , 35 ]. Cancer stem cells (CSC) could also have a role in radiation therapy resistance [ 36 ]. CSC can self-renew and initiate subpopulations of differential progeny, and a hypoxic microenvironment is ideal for CSC survival and proliferation [ 37 , 38 ].

Radiation therapy is used to treat all BC subtypes, but its implication is more important for TNBC, as there is no personalized therapy for this subtype. It has been shown that radiotherapy benefits TNBC patients both after conserving surgery and mastectomy [ 39 ].

2.3. Chemotherapy

BC chemotherapy comprises several families of cytotoxic drugs, including alkylating agents, antimetabolites and tubulin inhibitors [ 40 ]. Cyclophosphamide is a nitrogen mustard alkylating agent causing breakage of the DNA strands [ 41 ]. The mechanism of action for anthracyclines (doxorubicin, daunorubicin, epirubicin, and idarubicin) includes DNA intercalation, thereby inhibiting macromolecular biosynthesis [ 42 ]. Taxanes, including docetaxel and paclitaxel, bind to microtubules and prevent their disassembly, leading to cell cycle arrest and apoptosis [ 43 ].

Chemotherapy can be administered in the neoadjuvant or adjuvant setting and for metastatic BC treatment.

2.3.1. Neoadjuvant Chemotherapy (NAC)

Neoadjuvant chemotherapy was initially administered for non-metastatic but inoperable BC, defined as unreachable tumors [ 44 ]. Then, chemotherapy was used before the surgery for operable tumors to facilitate breast conservation [ 45 ].

Studies demonstrated that chemotherapy administered before surgery is as effective as administered after surgery [ 46 , 47 , 48 ]. The NSABP-B-18 trial compared the effects of doxorubicin and cyclophosphamide administered either postoperatively or preoperatively. This trial showed that NAC reduces the rate of axillary metastases in node-negative BC patients [ 48 ].

Some patients fail to achieve pathologic complete response after a full course of NAC. Unfortunately, there is no consensus regarding the treatment strategy to follow for patients with residual disease after surgery [ 49 , 50 ]. The BC subtype plays an important role in the response to NAC. Indeed, TNBC and HER2+ BC are more likely to be sensitive to chemotherapy. Hence, NAC is a good strategy to maximize pathologic complete response in these BC subtypes [ 45 ].

2.3.2. Adjuvant Chemotherapy

Adjuvant chemotherapy is administered to BC patients with lymph nodes metastases or a high risk of recurrence [ 51 ]. The standard chemotherapy treatment comprises an anthracycline and a taxane. The two most common regimens are cyclophosphamide and doxorubicin for four cycles followed by paclitaxel for four cycles. Then patients are given the previous combination of therapies followed by either weekly paclitaxel for 12 weeks, or docetaxel every 3 weeks for four cycles [ 52 , 53 ].

Like neoadjuvant therapy, patients with HR-negative BC receive more benefits from adjuvant therapy (i.e., reduction of BC recurrence and mortality) than HR+ BC patients [ 54 ]. However, for patients with HR+, node-negative BC associated with a high Oncotype recurrence score (≥31), calculated from the expression of 16 BC-related genes and 5 reference genes, adjuvant chemotherapy reduces the risk of recurrence [ 55 ]. The TAILORx clinical trial showed that HR+ BC patients with a low Oncotype recurrence score do not benefit from chemotherapy alone [ 56 ].

According to the molecular BC subtype, chemotherapy can be administered with targeted therapies. Patients with HR+ BC should receive endocrine therapy after chemotherapy is completed, and HER2+ BC patients should receive trastuzumab combined with chemotherapy [ 57 ]. For TNBC patients, front-line therapy includes a combination of taxane and anthracycline [ 58 ].

One of the major drawbacks of chemotherapy is its side effects. The early side effects (0–6 months of treatment) involve fatigue, alopecia, cytopenia (reduction in the number of normal blood cells), muscle pain, neurocognitive dysfunction, and chemo-induced peripheral neuropathy. The chronic or late side effects (after 6 months of treatment) include cardiomyopathy, second cancers, early menopause, sterility, and psychosocial impacts [ 59 ].

As mentioned previously in this review, chemotherapy is composed of taxanes, anthracyclines and cyclophosphamide. Each of these molecules can lead to resistance in BC patients [ 60 ].

One mechanism of resistance is by overexpressing p-glycoprotein, an ATP-binding cassette (ABC) family member, which confers resistance to anthracycline and taxanes [ 61 ]. Breast cancer resistance protein (BCRP), another ABC family member, induces resistance to anthracycline but not taxanes when overexpressed [ 62 ]. Microtubule alterations can also lead to taxane resistance. The overexpression of β-tubulin III induces paclitaxel resistance [ 63 ]. Moreover, mutations in microtubule-associated proteins (MAPs) affect microtubule dynamics and improve taxane resistance [ 64 ]. Multiple enzymes are known to be involved in the cyclophosphamide detoxification, leading to its resistance. For example, aldehyde dehydrogenase upregulation detoxifies aldophosphamide a type of cyclophosphamide, and mutations in glutathione S-transferases, enzymes involved in drug-metabolizing conjugation reactions, can also affect cyclophosphamide detoxification [ 65 , 66 ].

Surgery, radiotherapy, and chemotherapy are complementary strategies in the treatment of BC patients. However, they are not sufficient to effectively treat all BC molecular subtypes, as they do not have the same response to radiotherapy or chemotherapy. Thus, personalized therapies are essential in the process for BC treatment.

3. Current Personalized Treatments for Breast Cancer: Strengths and Weaknesses

The current strategies of treatment are principally based on the tumor progression and BC molecular subtypes in order to offer the most personalized treatment for BC patients. The algorithm of BC treatment is represented in Figure 2 .

Breast cancer treatment flow diagram. ( A ). Early-stage breast cancer. ( B ). Metastatic/advanced breast cancer. a Neoadjuvant chemotherapy for HR+ BC patients is not systematic. It is mainly administered to luminal B BC patients and/or elder BC patients. HR+: hormone receptors positive; HER2+: human epidermal growth factor receptor 2 positive; TNBC: triple-negative breast cancer; AIs: aromatase inhibitors; T-DM1: trastuzumab-emtansine.

3.1. Endocrine Therapy

Endocrine therapy is the main strategy to treat HR positive invasive BC. The purpose of this therapy is to target the ER directly (selective estrogen receptors modulators and degraders) or the estrogen synthesis (aromatase inhibitors) [ 67 ]. The most common types of endocrine therapy are selective estrogen receptor modulators (SERMs), selective modulators estrogen receptor degraders (SERDs), and aromatase inhibitors (AIs) [ 68 ]. Endocrine therapy mechanism of action and resistance are described in Figure 3 .

Endocrine therapy mechanisms of action and resistance. The left part of the figure shows the mechanism of endocrine therapy through aromatase inhibitors, tamoxifen, and fulvestrant. The right part of the figure describes the mechanisms of resistance to endocrine therapy through the epigenetic modifications, the increase of coactivators and cell cycle actors, and the activation of other signaling pathways. Estrogens can go through the plasma membrane by a. diffusion as they are small non-polar lipid soluble molecules; b. binding to membrane ER initiating the activation of Ras/Raf/MAPK and PI3K/Akt signaling pathways which are blocked by tamoxifen. 1: inhibition of ER dimerization; 2: blockage of nucleus access; 3: ER degradation. ER: estrogen receptor; AIB1: amplified in breast cancer 1; IGF-1R: insulin growth factor receptor 1; IGF: insulin growth factor; HER: human epidermal receptors; EGF: epidermal growth factor; HB-EGF: heparin-binding EGF-like growth factor; TGF-α: transforming growth factor alpha; MEK/MAPK: mitogen activated protein kinase; PI3K: phosphoinositide 3-kinase; mTOR: mammalian target of rapamycin; Me: methylation; Ac: acetylation.

3.1.1. Selective Estrogen Receptor Modulators (SERMs)

SERMs, such as tamoxifen, toremifene, bazedoxifene, and raloxifene, are antiestrogens that compete with estrogen by binding to the ER. This binding changes the conformation of the ER ligand-binding domain, and once ER is translocated to the nucleus, it blocks co-factor recruitment and subsequent genes transcription involved in cell cycle progression (cyclin D1), cell proliferation (like IGF-1), or cell migration (collagenase) [ 69 , 70 ].

The most used SERMs is tamoxifen, approved by the US Food and Drugs Administration (FDA) in 1977. It is an adjuvant therapy orally administered for 5 to 10 years according to tumor aggressivity. Tamoxifen adjuvant treatment reduces recurrence risk by 50% for the first 5 years and 30% for the next 5 years [ 71 ]. Tamoxifen is given to either premenopausal or postmenopausal patients. However, for high-risk premenopausal patients, adding ovarian suppression is more effective than tamoxifen alone [ 72 ]. Tamoxifen can also be administered as neoadjuvant treatment, especially for elderly BC patients [ 73 ]. However, studies have demonstrated no difference in OS for ER+ BC patients when neoadjuvant tamoxifen is compared to surgery [ 74 , 75 ].

Other SERMs have since been developed, such as toremifene approved by the FDA in 1997 [ 76 ]. Studies comparing the effect of toremifene and tamoxifen in premenopausal patients with ER+ advanced BC have shown that toremifene efficacy and safety are similar to tamoxifen [ 77 , 78 ]. Bazedoxifene and raloxifene are administered as prevention treatment to postmenopausal patients at high risk of developing invasive BC and for preventing osteoporosis [ 79 , 80 , 81 ].

The most frequent adverse events of SERMs are hot flushes, nausea, vomiting, vaginal bleeding/discharges, and increased risk of thromboembolic events [ 82 ]. Of note, about 40% of HR+ BC patients will develop resistance to SERMs [ 83 ]. SERMs resistance can occur by the loss of ER expression or functions. Epigenetic modifications such as hypermethylation of CpG islands or histone deacetylation can lead to transcriptional repression of ER [ 84 ]. Another potential mechanism for ER expression loss is the overpopulation of ER-negative cells in heterogenous ER+ tumors [ 85 ]. Mutations in the ligand-binding domain of ER gene ( ESR1 ) inhibit the binding of estrogen to the ER leading to the abolition of downstream signaling. Moreover, abnormal splicing can lead to truncated, nonfunctional ER protein [ 86 , 87 ]. Another explanation for SERMs resistance is the abnormal expression of ER coregulators [ 88 ]. Coregulators are very important in the ER pathway as they can increase or decrease ER activity depending on incoming signals [ 89 ]. The most studied coregulator involved in SERMs resistance is the AIB1 (Amplified in breast cancer 1) coactivator protein, often overexpressed in resistant breast tumors [ 90 ]. In particular, in ER+ cells that overexpress HER2, there is a crosstalk between HER2 and AIB1. HER2 induces phosphorylation of AIB1 leading to evasion and subsequent activation of the ER signaling pathway even though it is inhibited by SERMs [ 91 ]

3.1.2. Selective Estrogen Receptor Degraders (SERDs)

To counteract the large proportion of tamoxifen-resistant tumors, a new type of therapeutic agents with a different mechanism of action has been developed: SERDs. In contrast to SERMs, SERDs completely block the ER signaling pathway.

Fulvestrant is the main SERD administered. It was discovered by Wakeling and collaborators in 1987 and demonstrated pure anti-estrogen activity [ 92 ]. Fulvestrant binds to ER with a higher affinity than tamoxifen. Once it binds to the ER, it inhibits receptor dimerization and then blocks ER translocation to the nucleus leading to its degradation [ 93 , 94 , 95 ].

Fulvestrant is administered by intramuscular injections, and common adverse effects are nausea, pain, and headaches [ 96 ]. Fulvestrant is approved to treat postmenopausal and premenopausal patients with ovarian function suppression, with ER+ advanced or metastatic BC on prior endocrine therapy [ 97 ]. More recently (in 2017), fulvestrant was approved as first-line monotherapy for advanced ER+ breast cancer [ 98 ]. According to the 2021 NCCN guidelines, fulvestrant combined with endocrine therapy or CDK4/6 inhibitors is one of the preferred regimens for second-line therapy in ER+ advanced or metastatic BC [ 99 ]. The combination of fulvestrant with other endocrine therapies has not shown any advantages over fulvestrant used in monotherapy [ 100 , 101 ]. Clinical studies have shown benefits from fulvestrant when administered in higher doses to patients with ESR1 -mutated advanced BC [ 102 , 103 ]. Indeed, ESR1 mutations occur in nearly 20% of cases of ER+ BC [ 86 ].

However, fulvestrant can lead to resistance by different mechanisms. For example, by upregulating the PI3K (phosphatidylinositol 3-kinase), mTOR (mammalian target of rapamycin) and Ras-ERK (extracellular signal-regulated kinase) signaling pathways. PI3K/Akt/mTOR is a downstream signaling pathway of ER activation and plays an important role in antiestrogen therapy resistance [ 104 ]. PI3K pathway activation can occur independently of ER by binding to the epidermal growth factor (EGF) [ 105 ]. Moreover, it has been shown that Akt overexpression leads to fulvestrant resistance [ 106 ]. IGF-1R activation (insulin-like growth factor 1 receptor) may be another mechanism of resistance to fulvestrant. IGF-1R expression is involved in cell survival and promotes metastatic cell proliferation. The interaction between IGF-1R and ER initiates the activation of IGF-1R/MAPK (mitogen-activated protein kinase) and IGF-1R/PI3K signaling leading to antiestrogen resistance [ 107 ].

3.1.3. Aromatase Inhibitors (AIs)

Aromatase is a cytochrome P50 enzyme involved in the synthesis of androgens and estrogens [ 108 ]. Aromatase is found in the breast, uterus, and other estrogen-sensitive tissues in specific levels depending on menopausal status [ 109 , 110 ]. Aromatase expression is increased in breast tumors and associated with high estrogen levels. Therefore, high expression of aromatase promotes ER+ tumor proliferation [ 111 ].

Aromatase inhibitors (AIs) block aromatase enzyme activity, leading to the inhibition of estrogen synthesis. Current AIs can be classified into two categories: steroidal AIs and non-steroidal AIs [ 112 ]. Exemestane, a steroidal AI, has a steroid-like structure similar to androstenedione, which is the aromatase substrate. Exemestane irreversibly binds to the aromatase substrate-binding site leading to its inactivation [ 113 ]. Non-steroidal AIs include letrozole and anastrozole. They both bind non-covalently and competitively to the aromatase substrate-binding site and prevent the binding of androgens by saturating the binding site [ 112 ].

AIs are an oral treatment administered only to postmenopausal women (including patients that become postmenopausal following ovarian suppression). It is administered alone or in combination with tamoxifen as adjuvant therapy for HR+ BC patients [ 114 , 115 , 116 , 117 ]. AIs can be administered for 5 years or 2–3 years if followed by tamoxifen and up to 5 years after previous tamoxifen or AI treatment. For advanced or metastatic HR+ BC, AIs can be delivered as first-line and second-line therapy. Patients who become postmenopausal after or during the 5 years of tamoxifen treatment can receive AIs, such as letrozole, as an extended treatment strategy [ 118 , 119 ].

Estrogens have protective effects on the cardiovascular system by regulating serum lipids concentrations and increasing vasodilatation [ 120 ]. Hence, AIs might increase the risk of developing cardiovascular diseases by reducing estrogen levels in the blood [ 121 ]. Other adverse effects of AIs include hot flushes, vaginal dryness, fatigue, and osteoporosis [ 122 ]. ER+ tumors can acquire AI resistance. Some mechanisms of AI resistance are similar to those conferring SERM or SERD resistance, such as ESR1 mutations, epigenetic modifications, and PI3K pathway upregulation [ 123 ]. However, other mechanisms of action are involved in AI resistance. For example, the upregulation of cyclin-dependent kinase 4 (CDK4) or cyclin-dependent kinase 6-retinoblastoma (CDK6-RB) pathways can lead to an estrogen-dependent cell progression [ 124 ]. Clinical studies have shown better benefits from CDK4-CDK6 inhibitors in combination with AIs compared to AIs alone [ 125 , 126 ].

Endocrine therapy is a well-established treatment strategy for HR+ tumors. Over the last decades, SERMs, SERDs and AIs have been proven as safe and effective personalized therapy for HR+ BC patients, and these therapeutic strategies have shown continued improvements. However, the main drawback of endocrine therapy is acquired or de novo resistance [ 127 ]. Hence, it is essential to develop new therapeutic agents that use different modes of action to treat HR+ BC more efficiently.

3.2. Anti-HER2 Therapy

The overexpression of HER2 is associated with worse survival outcome compared to HR-positive/HER2-negative BC [ 128 , 129 ]. Hence, therapies targeting HER2 are essential to treat HER2-positive BC. The current anti-HER2 therapies comprise antibodies that target specific HER2 epitopes, tyrosine kinase inhibitors (TKIs) and, more recently, antibody-drug conjugates (ADCs) [ 130 ]. Anti-HER2 mechanisms of action and resistance are described in Figure 4 .

Anti-HER2 therapy mechanisms of action and resistance. The left part of the figure describes the mechanism of action of anti-HER2 therapy through anti-HER2 antibody (trastuzumab and pertuzumab), tyrosine kinase inhibitors (lapatinib and nerotinib), and trastuzumab-emtansine (T-DM1). The right part of the figure describes the mechanism of resistance to anti-HER2 therapy through constitutive active p95 HER2 fragment, activation of other signaling pathways, and rapid recycling of HER2-T-DM1. ADCC: antibody-dependent cellular cytotoxicity; HER2: human epidermal growth factor receptor 2; EGF: epidermal growth factor, HB-EGF: heparin-binding EGF-like growth factor; TGF-α: transforming growth factor alpha; T-DM1: trastuzumab-emtansine; IGF-1R: insulin growth factor receptor 1; IGF: insulin growth factor; HGF: hepatocyte growth factor; MEK/MAPK: mitogen activated protein kinase; PI3K: phosphoinositide 3-kinase; mTOR: mammalian target of rapamycin; PTEN: phosphatase and tensin homolog.

3.2.1. Antibodies Targeting HER2

The first developed HER2-targeted antibody, trastuzumab (Herceptin), was approved by the FDA in 1998 [ 131 , 132 ]. Trastuzumab targets subdomain IV of the HER2 extracellular domain. However, the mechanism underlying trastuzumab’s therapeutic effect is not well understood. Multiple studies have reported hypotheses to explain trastuzumab’s mechanism of action. For instance, trastuzumab may inhibit the formation of the HER2-HER3 heterodimer, known to be the most oncogenic pair in the HER family [ 133 ]. It could also inhibit the formation of the active p95 HER2 fragment by preventing cleavage of the HER2 extracellular domain [ 134 ]. An indirect antitumor effect could be activating antibody-dependent cellular cytotoxicity (ADCC) by engaging with Fc receptors on immune effector cells [ 135 ].

Initially, trastuzumab was approved for administration in metastatic HER2+ BC, increasing the clinical benefits of first-line chemotherapy [ 132 ]. Trastuzumab has also demonstrated its efficacy and safety in early-stage HER2+ BC. It is given as neoadjuvant or adjuvant therapy in combination with other anti-HER2 treatments and/or with chemotherapy [ 136 , 137 , 138 ]. The recommended dose for intravenous trastuzumab is 4 mg/kg followed by 2 mg/kg weekly for 1 year in the adjuvant setting for early-stage HER2+ BC and until disease-free progression for metastatic HER2+ BC [ 139 ].

Pertuzumab (Perjeta) is another antibody that targets the HER2 extracellular domain but binds to subdomain II. Once it binds to HER2, pertuzumab prevents HER2 heterodimerization with other HER family members, leading to inhibition of downstream signaling pathways [ 140 ]. Like trastuzumab, one of pertuzumab’s indirect antitumor effects is activating the ADCC pathway [ 141 ]. Multiple clinical trials have shown that pertuzumab, combined with trastuzumab and chemotherapy, improved OS in metastatic HER2+ BC patients compared to trastuzumab and chemotherapy alone [ 142 , 143 , 144 , 145 ]. The benefits of pertuzumab have also been shown in early-stage HER2+ BC, as pertuzumab can be used in the neoadjuvant or adjuvant setting combined with trastuzumab and chemotherapy [ 146 , 147 , 148 , 149 ]. Pertuzumab is administered in fixed doses of 840 mg followed by 420 mg every three weeks [ 150 ].

Despite the major positive impacts of trastuzumab and pertuzumab in HER2+ BC treatment, only one-third of BC patients with HER2+ tumors benefit from anti-HER2 antibodies [ 151 ]. One of the hypotheses explaining this resistance concerns structural modifications of HER2, which hinder antibody binding. Alternative splicing can lead to a truncated isoform lacking the extracellular domain, thus forming a constitutive active p95 HER2 fragment [ 152 ]. The overexpression of other tyrosine kinases can bypass the signaling pathways mediated by HER2. It has been shown that cells overexpressing IGF-1R overcome cell cycle arrest by increasing CDK2 kinase activity [ 153 ]. Moreover, the overexpression of c-Met (a hepatic growth factor receptor) synergizes with HER2 signaling to confer resistance to anti-HER2 antibodies. Indeed, c-Met physically interacts with HER2, and c-Met depletion renders cells more sensitive to trastuzumab [ 154 , 155 ]. Another hypothesis for anti-HER2 antibody resistance is intracellular alterations in HER2 downstream signaling pathways. HER2 activates PI3K/Akt signaling, and PTEN (phosphatase and tensin homolog) is a well-known inhibitor of this pathway [ 156 ]. Tumors with a loss of PTEN function and/or constitutive activation of PI3K due to alteration mutations achieve worse therapeutic outcomes with trastuzumab [ 157 , 158 ].

3.2.2. Tyrosine Kinase Inhibitors (TKIs)

Since tumors may be resistant to anti-HER2 antibodies, new approaches have been developed. TKIs such as lapatinib, neratinib, or pyrotinib are small molecules that compete with ATP at the catalytic domain of the receptor to prevent tyrosine phosphorylation and HER2 downstream signaling [ 159 ].

Lapatinib is a dual EGFR/HER2 TKI blocking both HER1 and HER2 activation [ 160 ]. In metastatic BC, clinical trials have shown that lapatinib offers more benefits than chemotherapy alone [ 161 , 162 , 163 ]. The effects of lapatinib in the neoadjuvant/adjuvant setting have also been evaluated. As a neoadjuvant treatment, lapatinib plus trastuzumab combined with chemotherapy were more efficient than chemotherapy combined with lapatinib or trastuzumab alone [ 164 ]. Lapatinib as adjuvant treatment showed modest antitumor efficacy compared to placebo in a randomized, controlled, and multicenter phase III trial (TEACH) [ 165 ]. For luminal B (ER/PR+; HER2+) advanced or metastatic BC, lapatinib can be administered in combination with AIs.

Neratinib is an irreversible TKI targeting HER1, HER2, and HER4 [ 166 ]. The FDA approved Neratinib in 2017 as an extended adjuvant treatment for patients with HER2+ early-stage BC and combination with trastuzumab in the adjuvant setting [ 167 , 168 ]. Neratinib can be delivered in combination with capecitabine as a third-line and beyond therapy for HER2+ advanced or metastatic BC.

More recently, pyrotinib, a new generation TKI targeting HER1, HER2 and HER4, has been developed [ 169 ]. Pyrotinib is still under clinical trials to prove its efficacy and safety [ 170 ]. However, in 2018, the Chinese State Drug Administration approved pyrotinib in combination with or after chemotherapy treatment for patients with HER2+ advanced or metastatic BC [ 171 ].

Despite the recent development of TKI treatments, patients can still exhibit intrinsic or acquired resistance to these agents. Three mechanisms of action have been hypothesized: (1) activation of compensatory pathways, (2) HER2 tyrosine kinase domain mutation, and (3) other gene amplification [ 172 ]. For instance, activation of the PI3K/Akt pathway and FOXO3A (Forkhead transcription factor) by the upregulation of HER3 can lead to lapatinib resistance [ 173 ]. Other tyrosine kinases can be involved, such as c-Met, also known to be implicated in trastuzumab resistance. C-Met induces the activation of PI3K/Akt signaling in lapatinib-resistant BC [ 174 ]. Mutations in the HER2 tyrosine kinase domain lead to the constitutive activation of HER2 by substituting individual amino acids [ 175 ]. Lastly, it has been shown that the amplification of the NIBP (TRAPPC9, Trafficking Protein Particle Complex 9) gene occurs in HER2+ lapatinib-resistant tumors. The inhibition of NIBP makes resistant cells sensitive to lapatinib [ 176 ].

3.2.3. Trastuzumab-Emtansine (T-DM1)

Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate (ADC), which is a conjugate of trastuzumab and a cytotoxic molecule, DM1, a derivative of maytansine [ 177 ]. T-DM1 binds to HER2 with the trastuzumab part. The formed complex is then internalized for degradation, releasing DM1 metabolites into the cytoplasm. DM1 then inhibits microtubule assembly causing cell death [ 178 , 179 ]. Thus, T-DM1 consists of the antitumor effects of trastuzumab and those associated with DM1 metabolites [ 180 ].

Three phase III clinical trials have evaluated the safety and efficacy of T-DM1 for HER2+ metastatic BC [ 181 , 182 , 183 ]. They have shown that T-DM1 improves OS and DFS of HER2+ metastatic BC patients compared to lapatinib in combination with trastuzumab or chemotherapy [ 181 , 182 , 183 ]. T-DM1 as neoadjuvant treatment has less efficacy compared with trastuzumab or pertuzumab with chemotherapy [ 146 ]. This suggests that T-DM1 should not be administered as a neoadjuvant treatment but as a first-line or second-line therapy for HER2+ metastatic BC. The 2021 NCCN guidelines recommend using T-DM1 as second-line therapy for HER2+ advanced or metastatic BC [ 99 ].

The mechanism of action of T-DM1 involves those related to trastuzumab and DM1, so the observed resistance to T-DM1 could come from interference in one or both constituents [ 184 ]. The mechanism of T-DM1 resistance has been hypothesized to involve (1) the loss of trastuzumab mediated activity, (2) the dysfunctional intracellular trafficking of T-DM1, and (3) the impairment of DM1 mediated cytotoxicity [ 185 ].

As previously described in this review, the reduction of trastuzumab effects can occur by reduced HER2 expression, dysregulation of PI3K signaling, or the activation of alternative tyrosine kinase receptors [ 153 , 154 , 156 , 186 ]. The alteration of HER2-T-DM1 complex internalization can go through a rapid recycling of HER2 to the plasma membrane leading to the inhibition of DM1 metabolism released into the cytoplasm [ 187 ]. The internalization of the HER2-T-DM1 complex occurs through the formation of lysosomes. These vesicles enclose lysosomal enzymes involved in HER2-T-DM1 complex degradation. In T-DM1-resistant tumors, the level of lysosomal enzymes is inhibited [ 188 , 189 ]. T-DM1 also disrupts microtubule assembly causing incomplete spindle formation resulting in mitotic catastrophe and apoptosis [ 190 ]. Cells resistant to T-DM1 can avoid this process by reducing the induction of Cyclin-B1, an enzyme essential for cell cycle progression [ 191 ].

HER2+ BC are aggressive and associated with poor prognosis and metastasis, and recurrences. Anti-HER2 therapy has greatly improved the management of HER2+ BC. However, 25% of early-stage HER2+ BC patients will have a recurrence after the initial anti-HER2 treatment [ 192 ]. The emergence of new therapeutic agents specific for HER2+ BC provides new hope to treat this particularly aggressive BC subtype.

3.3. PARP Inhibitors

The prevalence of BRCA (Breast Cancer genes) mutations in TNBC patients is approximately 20% [ 193 ]. BRCA1 and BRCA2 are proteins involved in the DNA damage response to repair DNA lesions [ 194 ]. Mutations in BRCA 1/2 genes are associated with an increased risk of breast and ovarian cancers [ 195 ].

PARP (poly-(ADP-ribose) polymerase protein) proteins are also involved in the DNA damage response as they recruit DNA repair proteins, such as BRCA1 and BRCA2, to the damage site [ 196 ]. PARP inhibitors (PARPi) were developed to inhibit DNA repair in BRCA-mutated BC since cells defective in BRCA functions cannot repair DNA damage when PARP is inhibited [ 197 ]. The principal PARPis currently in clinical development are olaparib, talazoparib, veliparib, and rucaparib [ 198 ]. PARP inhibitors mechanisms of action and resistance are described in Figure 5 .

PARP inhibitors mechanisms of action and resistance. The left part of the figure describes the mechanism of PARP inhibitors in the context of BRCA mutated breast cancer. The right part of the figure describes the mechanism of resistance to PARP inhibitors through secondary intragenic mutations restoring BRCA proteins functions and the decrease of the recruitment of nucleases (MUS81 or MRE11) to protect the replication fork. PARP: poly-(ADP-ribose) polymerase protein; PARPi: PARP inhibitors; BRCA: breast cancer protein; MUS81: methyl methanesulfonate ultraviolet sensitive gene clone 81; MRE11: meiotic recombination 11.

3.3.1. Olaparib

Olaparib is the first FDA-approved PARPi for the treatment of BRCA -mutated BC [ 199 ]. Phase I and phase II trials evaluating the effects of olaparib monotherapy in germline BRCA-mutated (gBRCAm) BC proved its clinical benefits by improving progression-free survival (PFS) [ 200 , 201 , 202 , 203 ]. The phase III, randomized, open-label, OlympiAD trial compared olaparib monotherapy vs. standard chemotherapy in patients with BRCA mutated HER2-negative BC. This trial showed that olaparib has better efficacy and tolerability than standard chemotherapy for this group of patients [ 204 ]. Olaparib has also been tested in combination with chemotherapy. A phase I study evaluated the effects of olaparib in combination with paclitaxel in unselected TNBC patients [ 205 ]. The overall response rate (ORR) for these patients was 37%. Two phase I studies evaluating the combination of olaparib with cisplatin or carboplatin in gBRCAm BC patients showed improved ORR [ 206 , 207 ].

3.3.2. Talazoparib

Talazoparib has the highest PARP-DNA trapping efficiency among the PARPis [ 208 ]. A phase II trial testing the effects of talazoparib on gBRCAm early-stage BC showed decreased tumor size in all patients included [ 209 ]. Other phase I and II trials with gBRCAm BC patients receiving talazoparib confirmed the efficiency of this PARPi [ 210 , 211 ]. The EMBRACA study, an open-label phase III trial, compared talazoparib monotherapy to chemotherapy in gBRCAm, HER2-negative BC patients [ 212 ]. PFS and ORR were improved with talazoparib compared to chemotherapy alone.

3.3.3. Veliparib

Veliparib has been mostly evaluated in combination with chemotherapy. For example, the phase II multicenter I-SPY2 trial tested the combination of veliparib and neoadjuvant chemotherapy in unselected TNBC patients [ 213 ]. The predicted complete response rate (pCR) was 51% with veliparib and chemotherapy vs. 26% in the control arm (chemotherapy alone). The phase II BROCADE study evaluated the combination of veliparib with carboplatin and paclitaxel in gBRCAm BC patients [ 214 ]. The ORR was improved with the combination of veliparib and chemotherapy compared to chemotherapy alone. Lastly, the phase III BRIGHTNESS study evaluated the addition of veliparib to carboplatin in the standard neoadjuvant chemotherapy setting [ 211 ]. The addition of veliparib showed no further benefit to chemotherapy.

3.3.4. Rucaparib

Rucaparib is the second PARPi that has been FDA approved for gBRCAm BC patients [ 215 ]. Intravenous rucaparib was tested in a phase II trial of gBRCAm BC patients [ 216 ]. Stable disease, meaning no tumor development, was reported in 44% of patients. Rucaparib was also tested in combination with chemotherapy in unselected TNBC patients [ 217 ]. This phase I study showed that rucaparib could be safely used in combination with chemotherapy. The phase II, a randomized BRE09-146 trial, evaluated rucaparib in combination with cisplatin vs. cisplatin alone in gBRCAm patients with residual disease following neoadjuvant therapy [ 218 ]. DFS was similar in the two arms, as low-dose rucaparib did not affect cisplatin toxicity. However, the rucaparib dose may not have been sufficient to inhibit PARP activity.

Tumor cells can become resistant to PARPi by different mechanisms [ 219 ].

First, secondary intragenic mutations that restore BRCA proteins functions can lead to PARPi resistance [ 220 ]. These genetic events can lead to the expression of nearly full-length proteins or full-length wild-type proteins with complete restored functions [ 221 ]. This has been reported mostly in ovarian cancer patients, and it has also been demonstrated in BC cell line models [ 222 ]. Tumor cells with missense mutations conserving the N-terminal and C-terminal domains of BRCA proteins also lead to poor PARPi response [ 223 ]. Another mechanism of action leading to PARPi resistance is decreased expression of PARP enzymes. Indeed, tumor cells with low PARP1 expression acquire resistance to veliparib [ 224 ].

In addition, tumor cells can find alternative mechanisms to protect the replication fork. It has been shown that PARPi-resistant cells can reduce the recruitment of the MRE11 (meiotic recombination 11) nuclease to the damage site, leading to the protection of the fork by blocking its access [ 225 ]. Another study has shown that BRCA2 -mutated tumors acquired PARPi resistance by reducing the recruitment of the MUS81 (methyl methanesulfonate ultraviolet sensitive gene clone 81) nuclease to protect the replication fork [ 226 ].

Chemotherapy has been the pioneer treatment strategy for TNBC for decades. The development of PARPis has been a major improvement in the treatment of TNBC and, more specifically, gBRCAm TNBC, as they have shown more benefits over chemotherapy [ 227 ]. However, TNBC is a heterogenous BC subtype, and PARPis cannot treat all TNBCs as it is administered only for gBRCAm TNBC [ 228 ]. Therefore, it is necessary to develop specific targeted therapies to treat each TNBC subtype.

4. New Strategies and Challenges for Breast Cancer Treatment

4.1. emerging therapies for hr-positive breast cancer.

As mentioned in Section 3.1 , the major mechanisms of action of current endocrine therapy resistance occur via (1) the mTOR/PI3K/Akt signaling pathway and (2) the actors of the cell cycle progression CDK4/6. Therefore, emerging therapies for HR+ BC mainly target these pathways to bypass estrogen-independent cell survival [ 229 ]. The most recent completed clinical trials on emerging therapies for HR+ BC are presented in Table 1 .

Most recent completed clinical trial on emerging therapies for HR-positive breast cancer.

HR+: hormone receptors positive; HER2-: human epidermal growth factor receptor 2 negative; MBC: metastatic breast cancer; BC: breast cancer; PFS: progression free survival; CBR: clinical benefit rate; ORR: objective response rate; pCR: pathologic complete response; HR: hazard ratio.

4.1.1. mTOR/PI3K/AKT Pathway Inhibitors

The mTOR/PI3K/Akt pathway inhibitors can be divided into different categories according to the target in the pathway. Specific inhibitors have been developed to target all or specific isoforms of PI3K, mTORC1 and Akt [ 251 ].

Pan-Pi3K Inhibitors

Pan-PI3K inhibitors target all PI3K isoforms resulting in significant off-target effects. The main pan-PI3K inhibitors are buparlisib and pictilisib [ 252 ]. Multiple clinical trials have tested the effects of pan-PI3K inhibitors in luminal BC.

The phase III randomized double-blinded BELLE-2 trial compared buparlisib combined with fulvestrant, to fulvestrant monotherapy in luminal A advanced or metastatic BC patients [ 230 ]. The results of this trial showed a modest improvement in PFS when buparlisib was added to fulvestrant. Another phase III clinical trial (BELLE-3) studied the effects of buparlisib plus fulvestrant in luminal A advanced or metastatic BC patients with no benefits from endocrine therapy [ 231 ]. Though PFS was significantly improved with buparlisib, there were severe adverse effects such as hyperglycemia, dyspnea, or pleural effusion. Lastly, the phase II/III BELLE-4 clinical trial evaluated buparlisib plus paclitaxel in HER2-negative locally advanced or metastatic BC patients [ 232 ]. The addition of buparlisib to paclitaxel did not improve PFS in these patients. Thus, further studies on buparlisib in HR+ BC were not conducted. The phase II randomized, double-blinded FERGI clinical trial analyzed the effects of pictilisib plus fulvestrant in luminal A BC patients resistant to AI [ 233 ]. The addition of pictilisib to fulvestrant did not improve PFS. Moreover, severe adverse effects occurred when the dose of pictilisib was increased. These results were confirmed for pictilisib plus paclitaxel, as the phase II PEGGY study showed no benefit from pictilisib in PI3K-mutated HER2-negative BC patients [ 234 ].

Hence, pan-PI3K inhibitors are not optimal to treat HR+ BC due to their toxicity and lack of efficacy.

Isoform-Specific PI3K Inhibitors

To sort out issues related to off-target effects and toxicities with pan-PI3K inhibitors, isoform-specific PI3K inhibitors have been developed. These isoform-specific PI3K inhibitors can specifically target the PI3K p110α, p110β, p110δ, and p110γ isoforms [ 252 ]. Multiple clinical trials have tested the effects of isoform-specific PI3K inhibitors.

PI3K p110α is the most commonly mutated isoform in BC [ 253 ]. Alpelisib is the first FDA-approved PI3K p110α isoform inhibitor. A phase Ib clinical trial tested the effects of alpelisib and letrozole in patients with ER+ metastatic BC refractory to endocrine therapy [ 235 ]. The clinical benefit of the alpselisib and letrozole combination was higher for patients with PI3K-mutated BC, but clinical activity was still observed in patients with non-mutated tumors. The phase III randomized SOLAR-1 clinical trial compared the effects of alpelisib plus fulvestrant to fulvestrant alone in luminal A advanced BC patients who received no benefits from prior endocrine therapy [ 236 ]. The addition of alpelisib improved PFS for patients with PI3K-mutated BC.

Taselisib targets the PI3K p110α, p110γ and p110δ isoforms [ 254 ]. Taselisib was tested in the SANDPIPER study, a phase III randomized clinical trial, in combination with fulvestrant in patients with ER+ metastatic BC resistant to AIs [ 238 ]. Although the addition of taselisib slightly improved PFS, further clinical trials with taselisib were interrupted since high rates of severe adverse events were detected.

mTORC1 Inhibitors

mTORC1 inhibitors, such as everolimus, block the mTORC1 dependent phosphorylation of s6k1 [ 255 ]. The BOLERO-2 phase III randomized clinical trial investigated the effects of exemestane with or without everolimus in AI-resistant ER+ metastatic BC patients [ 240 ]. The combination of everolimus and exemestane improved PFS. The TAMRAD phase II randomized open-label study compared the effects of tamoxifen with or without everolimus in AI-resistant luminal A BC patients [ 241 ]. This study showed an improvement in overall survival (OS) when everolimus was given in combination with tamoxifen. The findings of these two clinical trials led to FDA approval of everolimus. More recently, the PrE0102 phase II randomized clinical trial showed that the addition of everolimus to fulvestrant improved PFS of patients with AI-resistant ER+ BC compared to fulvestrant alone [ 242 ].

Akt Inhibitors

Akt inhibitors target all Akt isoforms as Akt 1, 2, and 3 isoforms share very similar structures [ 256 ]. Capivasertib is the principal Akt inhibitor under investigation in different clinical trials. The FAKTION phase II multi-centered randomized clinical trial compared the effects of capivasertib plus fulvestrant to fulvestrant plus placebo in AI-resistant luminal A advanced BC patients [ 243 ]. PFS was significantly improved with the combination of capivasertib and fulvestrant in comparison with the placebo arm.

The AKT1 E17K activating mutation is the most common in Akt and occurs in approximately 7% of ER+ metastatic BC. This mutation in the Akt lipid-binding pocket leads to constitutive Akt activation by modifying its localization to the membrane [ 257 ]. A phase I study analyzed the effects of capivasertib alone or in combination with fulvestrant in a cohort of patients with AKT1 E17K mutation ER+ metastatic BC [ 244 ]. Capivasertib, in combination with fulvestrant, demonstrated clinically meaningful activity and better tolerability compared to capivasertib alone.

4.1.2. CDK4/6 Inhibitors

There are currently three CDK4/6 inhibitors approved to treat HR+/HER2- metastatic BC: palbociclib, ribociclib, and abemaciclib. They can be administered as first-line treatment combined with AIs or as second-line treatment combined with fulvestrant [ 258 ].

First-Line Treatment

Palbociclib, a highly selective CDK4/6 inhibitor, is the first FDA-approved CDK4/6 inhibitor as first-line treatment combined with AIs for metastatic or advanced HR+ BC patients [ 259 ].

PALOMA-1 is an open-label, randomized phase II study that evaluated the effects of palbociclib in combination with letrozole vs. letrozole alone as first-line treatment for HR+ advanced BC patients [ 126 ]. The addition of palbociclib to letrozole significantly improved PFS in HR+ BC patients. A phase III study was performed (PALOMA-2) to confirm these findings and expand the efficacy and safety of palbociclib, [ 245 ]. This double-blinded clinical trial tested the combination of palbociclib and letrozole in postmenopausal BC patients without prior systemic therapy for advanced BC. The addition of palbociclib to letrozole significantly improved PFS and ORR.

Ribociclib is the second FDA-approved CDK4/6 inhibitor for first-line treatment in postmenopausal advanced BC patients in combination with AIs [ 260 ]. The phase III MONALEESA-2 clinical trial results showed improved PFS and ORR with the combination of ribociclib and letrozole in HR+ metastatic BC patients. The clinical benefits and manageable tolerability observed with ribociclib and letrozole are maintained with longer follow-up compared to letrozole alone [ 247 ].

Abemaciclib has been tested in the phase III randomized double-blinded MONARCH-3 study [ 250 ]. HR+ advanced BC patients with no prior systemic therapy received abemaciclib plus anastrozole or letrozole or AIs plus placebo in the control arm. PFS and ORR were significantly improved with the combination of abemaciclib and AIs.

Second-Line Treatment

As second-line treatment, palbociclib can be given in combination with fulvestrant in advanced or metastatic BC patients with disease progression after endocrine therapy [ 261 ]. This was confirmed in the phase III multi-centered randomized double-blinded PALOMA-3 trial [ 246 ]. BC patients who received palbociclib plus fulvestrant had significantly longer PFS compared to fulvestrant plus placebo.

The phase III MONALEESA-3 study tested the effects of ribociclib plus fulvestrant in patients with HR+ advanced BC who received prior endocrine therapy in the advanced setting [ 248 ]. The PFS and ORR were significantly improved when ribociclib was added to fulvestrant. Thus, ribociclib plus fulvestrant can be considered as second-line treatment for these BC patients.

Abemaciclib has been recently approved in combination with fulvestrant for HR+ advanced or metastatic BC patients with disease progression after endocrine therapy. This was based on the results of the phase III, double-blinded MONARCH 2 study [ 249 ]. The combination of abemaciclib and fulvestrant demonstrated a significant improvement of PFS and ORR compared to fulvestrant plus placebo in HR+ metastatic BC patients who experienced relapse or progression after prior endocrine therapy.

mTOR/PI3K/Akt inhibitors and CDK4/6 inhibitors show great promise for advanced HR+ BC resistant to endocrine therapy. To leverage the potential of these two types of therapies, some preclinical studies have evaluated a triple therapy combination including PI3K inhibitors, CDK4/6 inhibitors, and endocrine therapy (see the summarized table at the end of the manuscript) [ 262 ].

4.2. New Strategic Therapies for HER2-Positive Breast Cancer

As mentioned in Section 3.2 , HER2+ BC is currently treated with specific HER2 targeting antibodies or tyrosine kinase inhibitors (TKIs), and more recently, with TDM-1, an antibody-drug conjugate. These treatments have greatly improved HER2+ BC survival. However, 25% of HER2+ BC patients will still develop resistance to anti-HER2 treatment. Hence, new therapeutic strategies are emerging, such as new antibodies targeting HER2, new TKIs, vaccines, and PI3K/mTOR and CDK4/6 inhibitors [ 263 ]. The most recent completed clinical trials on new strategies for HER2+ BC treatment are gathered in Table 2 .

Most recent completed clinical trials on emerging therapies for HER2+ breast cancer.

HER2+: human epidermal growth factor receptor 2 positive; ER+: estrogen receptor positive; HLA2/3: human leucocyte antigen 2/3; MBC: metastatic breast cancer; BC: breast cancer; PFS: progression free survival; CBR: clinical benefit rate; ORR: objective response rate; DFS: disease-free survival OS: overall survival GM-CSF: granulocyte macrophage colony-stimulated factor; HR: hazard ratio.

4.2.1. New Antibodies

Novel types of antibodies have been developed to target HER2+ BC more efficiently. They can be divided into three categories: antibody-drug conjugates (ADC), modified antibodies, and bispecific antibodies.

Antibody-Drug Conjugates (ADC)

ADCs are the combination of a specific monoclonal antibody and a cytotoxic drug that is released in the antigen-expressing cells [ 280 ]. The most common ADC is TDM-1, and the promising results with TDM-1 have led to the development of new ADCs.

Trastuzumab-deruxtecan (DS-8201a) is a HER2-targeting antibody (trastuzumab) linked to a DNA topoisomerase I inhibitor (deruxtecan) [ 281 ]. A phase I study demonstrated that DS-8201a had antitumor activity even with HER2 low-expressing tumors [ 282 ]. These results led to phase II and phase III clinical trials. The DESTINY-Breast01 clinical trial is an open-labeled, single-group, multicentered phase II study [ 264 ] was evaluated in HER2+ metastatic BC patients who received prior TDM-1 treatment. DS-8201a showed durable antitumor activity for these patients. Two phase III clinical trials are currently evaluating DS-8201a. DESTINY-Breast02 (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03523585","term_id":"NCT03523585"}} NCT03523585 ) is comparing DS-8201a to standard treatment (lapatinib or trastuzumab) in HER2+ metastatic BC patients previously treated with TDM-1. The DESTINY-Breast03 (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03529110","term_id":"NCT03529110"}} NCT03529110 ) trial is evaluating the effects of DS-8201a vs. TDM-1 in HER2+ metastatic BC patients with prior trastuzumab and taxane treatment.

Trastuzumab-duocarmycin (SYD985) is a HER-2 targeting antibody (trastuzumab) conjugate with a cleavable linker-duocarmycin payload that causes irreversible alkylation of the DNA in tumor cells leading to cell death [ 283 ]. A dose-escalation phase I study evaluated the effects of SYD85 in BC patients with variable HER2 status and refractory to standard cancer treatment [ 284 ]. Trastuzumab-duocarmycin showed clinical activity in heavily pretreated HER2+ metastatic BC patients, including TDM-1 resistant and HER2-low BC patients. After these promising results, a phase I expansion cohort study was performed on the same type of patients (heavily pretreated HER2+ or HER2-low BC patients) [ 265 ]. This study confirmed previous results on the efficacy of STD985. A phase III clinical trial (TULIP-ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03262935","term_id":"NCT03262935"}} NCT03262935 ) is ongoing to compare SYD985 to the treatment chosen by the physician in HER2+ metastatic BC patients. Other ADCs are under clinical trials to test their safety and activity for HER2+ advanced BC patients. RC48 is an anti-HER2 antibody conjugated with monomethyl auristatin E that demonstrated promising efficacy and a manageable safety profile in an open-labeled, multicentered phase II study (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT02881138","term_id":"NCT02881138"}} NCT02881138 ) [ 248 ]. PF06804103 conjugates an anti-HER2 monoclonal antibody and the cytotoxic agent, Aur0101. In a phase I study (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03284723","term_id":"NCT03284723"}} NCT03284723 ), PF06804103 showed manageable toxicity and promising antitumor activity [ 249 ]. XMT1522 showed encouraging results in a dose-escalation phase I study (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT02952729","term_id":"NCT02952729"}} NCT02952729 ) [ 250 ]. MEDI4276, which targets two different HER2 epitopes and is linked to a microtubule inhibitor, showed promising clinical activity in a phase I study (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT02576548","term_id":"NCT02576548"}} NCT02576548 ) [ 254 ] (see the summarized table at the end of the manuscript).

Chimeric Antibody

Margetuxumab (MGAH22) is a human/mouse chimeric IgG1 targeting HER2 monoclonal antibody. It is based on trastuzumab as it binds to the same epitope (subdomain IV or HER2 extracellular domain) but with an enhanced Fcγ domain. The substitution of five amino acids into the IgG1 Fc domain increases CD16A affinity, a receptor found on macrophages and natural-killer cells, and decreases CD32B affinity, leading to increased antibody-dependent cell-mediated cytotoxicity (ADCC) [ 285 ]. A phase I study evaluated margetuximab toxicity and tumor activity on HER2+ BC patients for whom no standard treatment was available [ 266 ]. This study showed promising single-agent activity of margetuximab as well as good tolerability. The phase III randomized open-labeled SOPHIA clinical trial (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02492711","term_id":"NCT02492711"}} NCT02492711 ) compared margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in pretreated HER2+ advanced BC patients [ 286 ]. The combination of margetuximab and chemotherapy significantly improved the PFS of patients compared to trastuzumab plus chemotherapy. This study is still under investigation to collect data on OS (see the summarized table at the end of the manuscript).

Bispecific Antibodies

Bispecific antibodies (BsAbs) can target two different epitopes in the same or different receptors by combining the functionality of two monoclonal antibodies [ 287 ]. MCLA-128 targets both HER2 and HER3 and have an enhanced ADCC activity [ 288 ]. A phase I/II study evaluated the safety, tolerability, and antitumor activity of MCLA-128 in patients with pretreated HER2+ metastatic BC.

Preliminary results showed encouraging clinical benefits of MCLA-128. An open-labeled, multicentered phase II study (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03321981","term_id":"NCT03321981"}} NCT03321981 ) is ongoing to evaluate the effects of MCLA-128 in combination with trastuzumab and chemotherapy in HER2+ metastatic BC patients.

ZW25 is a BsAb biparatopic that binds the IV and II subdomains of the HER2 extracellular domain, the binding epitopes of trastuzumab and pertuzumab, respectively [ 289 ]. The efficacy of ZW25 was evaluated in a phase I study given alone or in combination with chemotherapy in patients with advanced or metastatic HER2+ BC. The results of this study showed promising antitumor activity, and no-dose limiting was observed.

T-cell bispecific antibodies (TCBs) are another type of BsAbs recently developed. TCBs target the CD3-chain of the T-cell receptor and tumor-specific antigens, resulting in lymphocyte activation and tumor cell death [ 290 ].

GBR1302 targets both HER2 and CD3 receptors and directs T-cells to HER2+ tumor cells. A phase II study (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03983395","term_id":"NCT03983395"}} NCT03983395 ) is ongoing to determine the safety profile of the GBR1302 single agent in previously treated HER2+ metastatic BC. PRS-343 targets HER2 and the immune receptor CD137, a member of the tumor necrosis factor receptor family. Two clinical trials are investigating the effects of PRS-343 monotherapy (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03330561","term_id":"NCT03330561"}} NCT03330561 ) or in combination with other treatments (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03650348","term_id":"NCT03650348"}} NCT03650348 ) (see the summarized table at the end of the manuscript).

4.2.2. HER2-Derived Peptide Vaccines

One of the strategies of immunotherapy is activating the patient’s immune system to kill cancer cells. Vaccination is an emerging approach to induce a tumor-specific immune response by targeting tumor-associated antigens, such as HER2 [ 291 ]. HER2-derived peptide vaccines comprise different parts of the HER2 molecule, such as E75 (extracellular domain), GP2 (transmembrane domain), and AE37 (intracellular domain) [ 292 ].

E75 (HER2/neu 369–377: KIFGSLAFL) has high affinity for HLA2 and HLA3 (human leucocyte antigen) that can stimulate T-cells against HER2 overexpressing tumor cells [ 293 ]. The efficacy of the E75 vaccine to prevent BC recurrence has been evaluated in a phase I/II study, in which high-risk HER2+ HLA2/3+ BC patients received the E75 vaccine [ 269 ]. The results demonstrated the safety and clinical efficacy of the vaccine as PFS was improved in the E75-vaccinated group compared to the unvaccinated group. Other clinical trials are currently investigating the efficacy of the E75 vaccine on HER2+ BC (see he summarized table at the end of the manuscript).

GP2 (654-662: IISAVVGIL) is a subdominant epitope with poor affinity for HLA2 [ 294 ]. A phase I trial evaluating the effects of a GP2 vaccine in disease-free BC patients showed that it was safe and tolerable with HER2-specific immune response [ 295 ]. The GP2 vaccine has been tested in a randomized, open-labeled phase II study to prevent BC recurrence. The patients that received the GP2 vaccine had HER2+ and HLA2+ BC and were disease-free with a high risk of recurrence at the time of the study [ 270 ]. The results demonstrated that the GP2 vaccine was safe and clinically beneficial for patients with HER2+ BC who received the full vaccine series.

AE37 (Ii-key hybrid of MHC II peptide AE36 (HER2/neu 776–790)) can stimulate CD8+ and CD4+ cells. A randomized, single-blinded phase II study evaluated the effects of an AE37 vaccine to prevent BC recurrence. Patients with a high risk of recurrence and HER2+ BC received the AE37 vaccine [ 271 ]. The vaccination demonstrated no benefit in the overall intention-to-treat analysis, a method that considers the randomized treatment to avoid bias happening after the randomization [ 296 ]. However, the study showed that the AE37 vaccine was safe, and results suggested that it could be effective for HER2-low BC, such as TNBC.

4.2.3. New Tyrosine Kinase Inhibitors (TKIs)

As previously described in this review (see Section 3.2.2 Tyrosine kinase inhibitors (TKIs)), TKIs are small molecules targeting the HER2 intracellular catalytic domain [ 159 ]. New TKIs have been developed with better efficacy and less toxicity in the treatment of HER2+ metastatic BC, such as tucatinib and poziotinib.

Tucatinib is a TKI with high selectivity for HER2, leading to less EGFR-related toxicities, common with other HER TKIs [ 297 ]. A phase I dose-escalation trial evaluated the combination of tucatinib and trastuzumab in BC patients with progressive HER2+ brain metastases [ 298 ]. This study showed preliminary evidence of tucatinib efficacy and tolerability in these patients. Tucatinib was also tested in combination with TDM-1 in a phase Ib trial in HER2+ metastatic BC patients with heavy pre-treatment [ 299 ]. The combination of tucatinib and TDM-1 showed acceptable toxicity and antitumor activity in these patients. Tucatinib was FDA approved in combination with trastuzumab and capecitabine for patients with advanced or metastatic HER2+ BC who received prior anti-HER2 in the metastatic setting [ 300 ]. This was based on the results of the phase II HER2CLIMB clinical trial, where HER2+ metastatic BC patients received tucatinib or placebo in combination with trastuzumab and capecitabine [ 267 ]. The addition of tucatinib to trastuzumab and capecitabine improved PFS and OS of heavily pretreated HER2+ metastatic BC patients.

Poziotinib is a pan-HER kinase inhibitor that irreversibly inhibits the HER family members’ kinase activity [ 301 ]. A phase I study evaluated the efficacy and tolerability of poziotinib in advanced solid tumors. The results showed encouraging antitumor activity against different types of HER2+ cancers as poziotinib was safe and well-tolerated by the patients [ 302 ]. The phase II NOV120101-203 study evaluated the safety and efficacy of poziotinib monotherapy in heavily pretreated HER2+ metastatic BC patients [ 268 ]. Poziotinib showed meaningful activity in these patients with no severe toxicities.

4.2.4. mTOR/PI3K Inhibitors and CDK4/6 Inhibitors

As mentioned in the previous Section 4.1 , mTOR/PI3K inhibitors and CDK4/6 inhibitors have been evaluated as potential new strategic therapies for HR+ BC resistant to endocrine therapy. The mTOR/PI3K signaling pathway and CDK4/6 also play a role in the mechanisms leading to treatment resistance in HER2+ BC [ 303 ]. Thus, targeting them with mTOR/PI3K and CDK4/6 inhibitors is also being investigated in HER2+ BC subtype.

mTOR/PI3K Inhibitors

Alpelisib and taselisib are PI3K isoform-specific inhibitors that were also evaluated in HR+ BC [ 235 , 236 , 238 , 253 , 254 ]. A phase I study evaluated alpelisib in combination with trastuzumab and LJM716 (a HER3-targeted antibody) in patients with PI3KCA mutant HER2+ metastatic BC [ 272 ]. Unfortunately, the results of this study were limited by high gastrointestinal toxicity. Another phase I study tested alpelisib in combination with TDM-1 in HER2+ metastatic BC patients pretreated with trastuzumab [ 273 ]. The combination of alpelisib and TDM-1 demonstrated tolerability and antitumor activity in trastuzumab-resistant HER2+ metastatic BC patients. Taselisib is being tested in an ongoing phase Ib dose-escalation trial in combination with anti-HER2 therapies (trastuzumab, pertuzumab and TDM-1) in HER2+ advanced BC patients (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT02390427","term_id":"NCT02390427"}} NCT02390427 ).

Copanlisib is a highly selective and potent pan-class I PI3K inhibitor [ 304 ]. A phase Ib (PantHER) study evaluated the tolerability and activity of copanlisib in combination with trastuzumab in heavily pretreated HER2+ metastatic BC patients [ 274 ]. The combination of copanlisib and trastuzumab was safe and tolerable. Preliminary evidence of tumor stability was observed in these patients.

Everolimus is a mTORC1 inhibitor also tested in HR+ BC [ 240 , 241 , 242 ]. Everolimus was tested in phase III clinical trials, in combination with trastuzumab and docetaxel (BOLERO-1), or in combination with trastuzumab and vinorelbine (BOLERO-3) in trastuzumab-resistant advanced HER2+ BC [ 275 , 276 ]. Unfortunately, results showed an increase of adverse effects with everolimus. Moreover, the BOLERO-1 clinical trial showed no improvement in PFS with the combination of trastuzumab and everolimus. By contrast, PFS was significantly longer when everolimus was added to vinorelbine in BOLERO-3. A study analyzing the molecular alterations found in patients in the BOLERO-1 and BOLERO-3 clinical trials demonstrated that HER2+ BC patients could derive more benefit from everolimus if the tumors had PI3KCA mutations, PTEN loss or a hyperactive PI3K pathway [ 305 ].

CDK4/6 Inhibitors

Palbociclib, ribociclib and abemaciclib are CDK4/6 inhibitors that have been FDA approved to treat HR+ BC as first-line treatments [ 247 , 250 , 259 ]. They have also been evaluated in multiple clinical trials for advanced HER2+ BC. Palbociclib has been tested in combination with trastuzumab in the phase II SOLTI-1303 PATRICIA clinical trial in heavily pretreated advanced HER2+ BC patients [ 277 ]. Palbociclib combined with trastuzumab demonstrated safety and encouraging survival outcomes in these patients. Palbociclib has also been evaluated in combination with TDM-1 in HER2+ advanced BC patients pretreated with trastuzumab and taxane therapy [ 306 ]. The results of this phase I/Ib study showed safety, tolerability, and antitumor activity in these patients.

Ribociclib was evaluated in a phase Ib/II trial in combination with trastuzumab to treat advanced HER2+ BC patients previously treated with multiple anti-HER2 therapies [ 278 ]. The combination of ribociclib and trastuzumab was safe, but there was limited activity in heavily pretreated patients. The conclusions of this study suggest that CDK4/6 inhibitor/anti-HER2 combination should be administered in patients with few previous therapies.

Abemaciclib has been tested in the phase II randomized open-labeled MonarcHER trial in combination with trastuzumab with or without fulvestrant vs. trastuzumab with standard chemotherapy in HR+/HER2+ BC patients [ 279 ]. The combination of abemaciclib, trastuzumab, and fulvestrant significantly improved PFS in these patients, with a tolerable safety profile.

There are multiple ongoing clinical trials for advanced HER2+ BC testing the combination of palbociclib, trastuzumab, pertuzumab, and anastrozole (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03304080","term_id":"NCT03304080"}} NCT03304080 ); or palbociclib and trastuzumab plus letrozole (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03054363","term_id":"NCT03054363"}} NCT03054363 ). Preliminary results are expected around July 2021 and March 2022, respectively (see he summarized table at the end of the manuscript).

A great proportion of HER2+ BC patients develop resistance to traditional anti-HER2 therapies, and 40–50% of patients with advanced HER2+ BC develop brain metastases [ 307 ]. Thus, developing new therapies to overcome resistance is essential. The therapeutic strategies that have been described in this section provide new hope for HER2+ BC patients, especially for advanced or metastatic HER2+ BC patients.

4.3. Emerging Therapies for Triple Negative Breast Cancer (TNBC)

TNBC is the most aggressive BC subtype. The fact that TNBC lacks ER and PR expression and does not overexpress HER2, combined with its high heterogeneity, has contributed to the difficulties in developing efficient therapies [ 308 ]. Thus, multiple strategic therapies have been developed to treat all TNBC subtypes. These include conjugated antibodies, targeted therapy, and immunotherapy. An overview of the most recent and completed clinical trials on emerging therapies for TNBC is presented in Table 3 .

Most recent completed clinical trials on emerging therapies for TNBC.

TNBC: triple negative breast cancer; HER2: human epidermal growth factor receptor; HR: hormonal receptor; MBC: metastatic breast cancer; BC: breast cancer; AR: androgen receptor; PPV: personalized peptide vaccine; PFS: progression free survival; CBR: clinical benefit rate; ORR: objective response rate; IDFS: invasive disease-free survival; OS: overall survival; TTP: time to progression; pCR: pathologic complete response; HR: hazard ratio.

4.3.1. Antibodies-Drug Conjugates (ADC)

Antibody drug conjugates (ADCs) deliver a cytotoxic drug into the tumor cell by the specific binding of an antibody to a surface molecule [ 280 ]. Multiple ADCs have been investigated in TNBC such as sacituzumab govitecan, ladiratuzumab vedotin, or trastuzumab deruxtecan.

Sacituzumab govitecan combines an antibody targeting trophoblast antigen 2 (Trop-2) and a topoisomerase I inhibitor SN-38 [ 334 ]. Trop-2, a CA 2+ signal transducer, is expressed in 90% of TNBCs and is associated with poor prognosis [ 335 , 336 ]. A single-arm, multicentered phase I/II study evaluated sacituzumab govitecan in heavily pretreated metastatic TNBC patients [ 336 , 337 ]. The efficacy and safety of scituzumab govitecan was shown in these patients, as it was associated with durable objective response. Based on these results, a randomized phase III trial (ASCENT) tested sacituzumab govitecan compared to single-agent chemotherapy chosen by the physician in patients with relapsed or refractory metastatic TNBC [ 309 ]. Sacituzumab govitecan significantly improved PFS and OS of metastatic TNBC patients compared to chemotherapy.

Ladiratuzumab vedotin is composed of a monoclonal antibody targeting the zinc transporter LIV-1 and a potent microtubule disrupting agent, monoethyl auristatin E (MMAE) [ 338 ]. LIV-1 is a transmembrane protein with potent zinc transporter and metalloproteinase activity, expressed in more than 70% of metastatic TNBC tumors [ 339 ]. All clinical trials investigating ladiratuzumab vedotin are still ongoing. A dose-escalation phase I study is evaluating the safety and efficacy of ladiratuzumab vedotin in heavily pretreated metastatic TNBC patients (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT01969643","term_id":"NCT01969643"}} NCT01969643 ). Preliminary results showed encouraging antitumor activity and tolerability of ladiratuzumab vedotin with an objective response rate of 32% [ 340 ]. The estimated study completion date is June 2023. Two phase Ib/II trials are testing ladiratuzumab vedotin in combination with immunotherapy agents in metastatic TNBC patients, such as pembrolizumab (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03310957","term_id":"NCT03310957"}} NCT03310957 ) with expected preliminary results in February 2022, or in combination with multiple immunotherapy-based treatments (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03424005","term_id":"NCT03424005"}} NCT03424005 ) with expected preliminary results in January 2023.

Trastuzumab deruxtecan is an ADC developed as a treatment for metastatic HER2+ BC patients. Its mechanism of action is described in Section 3.2 . Even though trastuzumab deruxtecan was developed to treat HER2+ BC, it showed antitumor activity in HER2-low tumors in a phase I study [ 282 ]. Based on these results, an ongoing open-labeled, multicentered phase III study (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03734029","term_id":"NCT03734029"}} NCT03734029 ) is recruiting patients with HER2-low metastatic BC to test trastuzumab deruxtecan vs. standard treatment chosen by the physician. Preliminary results are expected in January 2023 (see Table 4 ).

Ongoing clinical trials on emerging therapies for BC treatment for all BC molecular subtypes.

TNBC: triple negative breast cancer; HER2: human epidermal growth factor receptor 2; ER: estrogen receptor; MBC: metastatic breast cancer; BC: breast cancer; HR: hormonal receptor; PFS: progression free survival; CBR: clinical benefit rate; ORR: objective response rate; DFS: disease-free survival; OS: overall survival; TTP: time to progression. pCR: pathologic complete response; GM-CSF: granulocyte macrophage colony-stimulated factor; DLT: dose-limiting toxicities; MTD: maximum tolerated dose; TTF: time to treatment failure; TTR: time to treatment response; iDFS: invasive disease-free survival; RFS: recurrence free survival; DDFS: distant disease-free survival; iEFS: invasive events-free survival; CR: clinical response; DoCB: duration of clinical benefit; SD: stable disease; DoR: duration of response; IAEs: incidence of adverse events; TDR: treatment discontinuation rate; PR: partial response; DCR: disease control rate; HR: hazard ratio.

4.3.2. Targeted Therapies

Targeted therapy is the current standard of care to treat HR+ and HER2+ BC, but it cannot be administered to patients with TNBC as these tumors lack the expression of these biomarkers. Hence, the next logical step is to identify biomarkers associated with TNBC to develop specific targeted therapies. Several emerging targeted therapies are being clinically trialed with limited or mixed results.

VEGF and EGFR Inhibitors

Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) are overexpressed in most TNBC patients [ 341 , 342 ]. Bevacizumab and cetuximab are antibodies developed to specifically target VEGF and EGFR, respectively. Unfortunately, clinical trials studying the effects of these antibodies in TNBC patients demonstrated limited results. The phase III, randomized BEATRICE study evaluating adjuvant bevacizumab-continuing therapy in TNBC demonstrated no significant benefit in OS [ 310 ]. A phase II trial evaluating the impact of adding bevacizumab or cisplatin to neoadjuvant chemotherapy to stage II to III TNBC concluded that further investigation of bevacizumab in this setting was unlikely [ 311 ].

The phase II randomized TBCRC 001 trial testing the combination of cetuximab and carboplatin in stage IV TNBC showed a response in fewer than 20% of patients [ 312 ]. Another randomized phase II study compared the effects of cetuximab plus cisplatin to cisplatin alone in metastatic TNBC patients. Adding cetuximab to cisplatin prolonged PFS and OS, warranting further investigation of cetuximab in TNBC [ 313 ]. Based on these results, bevacizumab is not recommended for the treatment of TNBC.

mTOR/PI3K/AKT Inhibitors

mTOR/PI3K/Akt signaling pathway is an important target involving all BC subtypes. Inhibitors of mTOR, PI3K, and Akt have been tested in HR+ and HER2+ BC patients and have also been tested in TNBC patients. The mTOR inhibitor everolimus has been tested in a randomized phase II trial in combination with chemotherapy vs. chemotherapy alone in stage II/III TNBC patients [ 314 ]. Unfortunately, the addition of everolimus was associated with more adverse effects, without improving pCR or clinical response. A phase I study testing the combination of everolimus and eribulin in metastatic TNBC patients showed that this combination was safe, but the efficacy was modest [ 343 ].

The Akt inhibitor ipatasertib has been tested in combination with paclitaxel (vs. placebo) for metastatic TNBC patients in the phase II multicentered double-blinded randomized LOTUS trial [ 315 ]. The results showed improved PFS when patients received ipatasertib. Another phase II double-blinded randomized trial, FAIRLANE, testing neoadjuvant ipatasertib plus paclitaxel for early TNBC, showed no clinically or statistically significant improvement in the pCR rate, but ipatasertib’s antitumor effect was more pronounced in patients with PI3K/AKT1/PTEN-altered tumors [ 316 ]. Capivasertib, another Akt inhibitor, has been tested in combination with paclitaxel (vs. placebo), first-line therapy for metastatic TNBC patients in the phase II double-blinded randomized PAKT trial [ 317 ]. The addition of capivasertib to paclitaxel significantly improved PFS and OS, with better benefits for patients with PI3K/AKT1/PTEN-altered tumors.

Androgen Receptor Inhibitors

The androgen receptor (AR) is a steroidal hormonal receptor that belongs to the nuclear receptor family and is expressed in 10% to 50% of TNBC tumors [ 344 ]. Tumors expressing AR have better prognosis but are less responsive to chemotherapy [ 345 ]. Multiple clinical trials have tested AR inhibitors in TNBC [ 318 , 319 , 320 ].

Bicalutamide, an AR agonist, was tested in a phase II study in patients with AR+, HR- metastatic BC [ 318 ]. The results showed promising efficacy and safety for these patients.

Enzalutamide, a nonsteroidal antiandrogen, has been tested in a phase II study in patients with locally advanced or metastatic AR+ TNBC [ 319 ]. Enzalutamide demonstrated significant clinical activity and tolerability, warranting further investigation.

Abiraterone, a selective inhibitor of CYP17, has been evaluated in combination with prednisone in AR+ locally advanced or metastatic TNBC patients [ 320 ]. This combination was beneficial for 20% of the patients.

Several clinical trials are currently testing AR inhibitors alone or combined with other treatments for TNBC patients; expecting results between 2022 and 2027 (see Table 4 ).

4.3.3. Immunotherapy

Targeted antibodies.

The immune system plays a crucial role in BC development and progression. Tumor cells can escape the immune system by regulating T-cell activity leading to the inhibition of immune response [ 346 , 347 ]. Two principal biomarkers found in TNBC are associated with this bypass: the programmed cell death protein receptor (PD-1) and its ligand PDL-1, and the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) [ 348 ].

PD-1 is an immune checkpoint receptor expressed on the surface of activated T-cells. PDL-1, its ligand, is expressed on the surface of dendritic cells or macrophages. The interaction of PD-1 and PDL-1 inhibits T-cell response [ 349 ]. CTLA-4 is expressed on T-cells and inhibits T-cell activation by binding to CD80/CD86, leading to decreased immune response [ 350 ].

Atezolizumab, an anti-PDL-1 antibody, has demonstrated safety and efficacy in a phase I study for metastatic TNBC patients [ 351 ]. Based on these results, atezolizumab was tested in combination with nab-paclitaxel for unresectable locally advanced or metastatic TNBC in the phase III double-blinded placebo-controlled randomized Impassion130 study [ 321 ]. Atezolizumab plus nab-paclitaxel prolonged PFS and OS in both the intention-to-treat population and PDL1+ subgroup. Another double-blinded, randomized phase III study (Impassion031) compared atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy vs. placebo for early-stage TNBC [ 322 ]. This combination significantly improved pCR with an acceptable safety profile.

Durvalumab, another anti-PDL-1 antibody, has been tested in combination with an anthracycline taxane-based neoadjuvant therapy for early TNBC in the randomized phase II GeparNuevo study [ 323 ]. This combination increased pCR rate, particularly in patients pretreated with durvalumab monotherapy before chemotherapy. Another randomized phase II study, SAFIRO BREAST-IMMUNO, compared durvalumab to maintenance chemotherapy in a cohort including TNBC patients [ 324 ]. Results showed that durvalumab, as a single agent therapy, could improve outcomes in TNBC patients. A phase I study tested durvalumab in combination with multiple TNBC therapies: PARP inhibitor olaparib and VEGFR1-3 inhibitor cediranib for patients with recurrent cancers including TNBC [ 325 ]. This combination was well tolerated and showed preliminary antitumor activity in all of these patients.

The safety and efficacy of avelumab, another anti-PDL-1 antibody, was evaluated in the phase Ib JAVELIN study in patients with locally advanced or metastatic BC, including TNBC [ 326 ]. Avelumab showed an acceptable safety profile and clinical activity, particularly in tumors expressing PDL-1.

Pembrolizumab is an anti-PD-1 antibody that has been tested in multiple clinical trials. The phase Ib KEYNOTE-012 study demonstrated the safety and efficacy of pembrolizumab on advanced TNBC patients [ 352 ]. Based on these results, the phase II KEYNOTE-086 study evaluated pembrolizumab monotherapy for pretreated or non-pretreated metastatic TNBC patients [ 327 , 353 ]. Pembrolizumab monotherapy showed a manageable safety profile and durable antitumor activity for both pretreated and non-pretreated subgroups. The randomized open-labeled phase III KEYNOTE-119 trial compared pembrolizumab monotherapy to standard chemotherapy in metastatic TNBC [ 354 ]. Pembrolizumab monotherapy did not significantly improve OS compared to chemotherapy in these patients. These findings suggest that pembrolizumab should be investigated in a combinational approach rather than in monotherapy. Based on these results, pembrolizumab was tested in combination with chemotherapy (vs. placebo) for pretreated locally recurrent or metastatic TNBC patients in the phase III double-blinded randomized KEYNOTE-355 trial [ 328 ]. The combination of pembrolizumab plus chemotherapy significantly and clinically improved PFS compared to chemotherapy plus placebo. Pembrolizumab has also been evaluated for early TNBC as neoadjuvant therapy in combination with chemotherapy (vs. placebo) in the phase III KEYNOTE-522 trial [ 329 ]. The combination of pembrolizumab plus chemotherapy significantly improved pCR rate in these patients compared to placebo plus chemotherapy.

Tremelimumab is an anti-CTLA-4 antibody. A dose-escalation phase I study evaluating the safety and efficacy of tremelimumab in patients with metastatic BC showed good tolerability [ 330 ].

Vaccination is an emerging approach to prevent recurrence in high-risk BC patients. As mentioned earlier, TNBC is the most aggressive BC subtype with a higher risk of distant recurrence [ 331 ]. Thus, developing vaccines to prevent recurrence in TNBC patients is of great interest.

Takahashi et al. have developed a novel regimen of personalized peptide vaccination (PPV) based on the patient’s immune system to select vaccine antigens from a pool of peptide candidates [ 332 ]. They performed a phase II study where metastatic recurrent BC patients with prior chemotherapy and/or hormonal therapies received a series of personalized vaccines. This vaccination demonstrated safety, possible clinical benefit, and immune response, especially for TNBC patients [ 332 ]. A multicentered, randomized, double-blinded phase III study analyzed the effects of sialyl-TN keyhole limpet hemocyanin (STn-KLH) on metastatic BC patients [ 333 ]. STn-KLH consists of a synthetic STn, an epitope expressed in BC and associated with aggressive and metastatic tumors, and a high molecular weight protein carrier KLH [ 355 ]. Stn-KLH demonstrated good tolerability, but no benefits in time to progression (TTP) or survival were found. Thus, this vaccination is not recommended for metastatic BC patients [ 333 ].

PVX-410 is a multiple peptide vaccine that activates T-cell to target tumor cells and was developed to treat myeloma. A phase Ib/II study demonstrated the safety and immunogenicity in myeloma patients [ 356 ]. Based on these results, a PVX-410 vaccine is currently being tested to treat TNBC in multiple clinical trials (see Table 4 ).

Finding new treatments for TNBC is an ongoing challenge. The therapeutic strategies that have been described in this section offer great hope to treat TNBC patients. However, because TNBC is highly heterogeneous, it is difficult to find a single treatment efficient for all TNBC subtypes [ 228 ].

5. Conclusions

This review clearly demonstrates that the treatment of BC is complex and is constantly evolving with a large number of ongoing clinical trials on emerging therapies. Indeed, the BC molecular subtype will determine the personalized therapeutic approach, such as targeted treatments like endocrine therapy for HR+ BC or anti-HER2 therapy for HER2+ BC. These therapies have demonstrated their safety and efficacy in treating BC over the years. However, it is essential to go beyond these conventional treatments as BC is a complex disease and not all patients can benefit from personalized treatment. One of the major challenges in BC treatment is finding effective therapies to treat TNBC patients since conventional targeted therapies cannot be administered for this specific BC subtype, which has the worst survival outcomes.

Another important issue in BC treatment is the acquisition of treatment resistance. This is a common phenomenon for either endocrine therapy, anti-HER2 therapy, and chemotherapy.

Hence, understanding the mechanisms underlying drug resistance is a good strategy to develop novel treatments for BC. For example, the mTOR/PI3K/Akt pathway is involved in the mechanism of resistance in all BC molecular subtypes, and thus developing specific inhibitors targeting this pathway is a promising BC treatment approach.

Acknowledgments

The authors would also like to thank team members from the C.D. and F.D. research groups for their valuable assistance.

Abbreviation

Author Contributions

A.B. conceptualized and drafted the manuscript. F.D. and C.D. supervised the project. All authors did critical revision of the manuscript. All authors have read and agreed to the published version of the manuscript.

This work was supported by the “Fond de recherche du Québec–Santé (FRQS)” associated with the Canadian Tumor Repository Network (CTRNet). Caroline Diorio is a senior Research Scholar from the FRSQ. Anna Burguin holds a Bourse d’excellence en recherche sur le cancer du sein—Faculté de médecine-Université Laval.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Data availability statement, conflicts of interest.

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Find Breast Cancer Clinical Trials That Are Right For You The clinical trials listed below are open in the U.S. for people with DCIS (stage 0), stage 1, stage 2, stage 3, or stage 4 (metastatic) breast cancer. Clinical trials are available for people who are newly diagnosed with breast cancer, currently in treatment, experiencing breast cancer recurrence, living with metastatic disease, as well as breast cancer survivors who have completed treatment. Use the search box and filters to find a trial that’s right for you.

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NEAREST SITE: 2 miles Zuckerberg San Francisco General Hospital San Francisco,CA

VISITS: 3 or 5 visits, over 5 years

NCT ID: NCT03233191

Breast Cancer Screening Based on Individual Risk Factors and Comparing the Effectiveness of 3D to 2D Mammography

Tomosynthesis Mammographic Imaging Screening Trial (TMIST) Scientific Title

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• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Digital mammogram (2D)</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">if you are premenopausal or postmenopausal with 1 risk factor, mammogram, once a year, for five years</li> <li class="seamTextUnorderedListItem">if you are postmenopausal, mammogram, every 2 years, for five years</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Digital tomosynthesis mammogram (3D)</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">if you are premenopausal or postmenopausal with 1 risk factor, mammogram, once a year, for five years</li> <li class="seamTextUnorderedListItem">if you are postmenopausal, mammogram, every 2 years, for five years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Most breast cancer screening guidelines are based upon a woman's age--not her individualized risk of developing breast cancer. </li> <li class="seamTextUnorderedListItem">For this trial, you will receive annual mammograms if you are premenopausal or postmenopausal with at least one risk factor.</li> <li class="seamTextUnorderedListItem">Risk factors if you are 45-69: dense breasts, a first degree relative with breast cancer, an inherited genetic mutation that increases your risk of developing cancer, or taking hormone therapy.</li> <li class="seamTextUnorderedListItem">Risk factors if you are 70-74: dense breasts or taking hormone therapy.</li> <li class="seamTextUnorderedListItem">Digital tomosynthesis (3D) mammography is approved by the FDA but is not considered the standard of care for breast cancer screening.</li> <li class="seamTextUnorderedListItem">Digital (2D) mammography is the standard of care for breast cancer screening.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03233191' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://ecog-acrin.org/tmist' target='_blank'>ECOG-ACRIN Cancer Research Group Trial Information Page: TMIST</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.breastcancer.org/symptoms/testing/types/dig_tomosynth' target='_blank'>Breastcancer.org: Digital Tomosynthesis</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/news-events/cancer-currents-blog/2017/tmist-breast-cancer-screening' target='_blank'>NCI Cancer Currents Blog: TMIST Trial Aims to Provide Clarity on Breast Cancer Screening Approaches</a> </li></ul>

VISITS: 1 visit every 3 weeks, for 10 months

NCT ID: NCT04457596

Two Therapies for People with Stage II-III HER2+ Breast Cancer Who Had Leftover Tumor after Receiving Neoadjuvant Therapy and Surgery

The CompassHER2 Trials (Comprehensive Use of Pathologic Response Assessment to Optimize Therapy in HER2-Positive Breast Cancer) CompassHER2 Residual Disease (RD), a Double-Blinded, Phase III Randomized Trial of T-DM1 Compared With T-DM1 and Tucatinib Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups and receive the following for up to 10 months: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab emtansine/T-DM1 (Kadcyla®), by IV, every 3 weeks</li> <li class="seamTextUnorderedListItem">Placebo, by mouth, twice daily, </li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab emtansine/T-DM1 (Kadcyla®), by IV, every 3 weeks</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®), by mouth, twice daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®) is an anti-HER2-targeted therapy approved for use with specific other therapies. Its use in this trial is considered experimental.</li> <li class="seamTextUnorderedListItem">Trastuzumab emtansine/T-DM1 (Kadcyla®) is an antibody-drug conjugate (ADC). It uses an antibody -— the HER2-targeted therapy trastuzumab (Herceptin®) -- to directly deliver the chemotherapy DM1 to the cancer cells. It is approved for use in people who had some leftover tumor (residual disease) after receiving neoadjuvant (before surgery) therapies, but its use in this trial is considered experimental.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04457596' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-terms/def/residual-disease' target='_blank'>NCI Dictionary of Cancer Terms: Residual Disease</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/news-events/cancer-currents-blog/2019/kadcyla-fda-breast-her2-adjuvant' target='_blank'>NCI Cancer Currents Blog: T-DM1 Approval Expanded to Include Some Women with Early-Stage HER2-Positive Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted_therapies/kadcyla' target='_blank'>Breastcancer.org: Kadcyla (Trastuzumab emtansine/T-DM1)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/druglist/tukysa' target='_blank'>Breastcancer.org: Tukysa (Tucatinib)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.onclive.com/view/personalizing-her2-targeted-treatment-strategies-in-early-stage-and-advanced-breast-cancer' target='_blank'>OncLive: Personalizing HER2-Targeted Treatment Strategies in Early-Stage and Advanced Breast Cancer</a> </li></ul>

NEAREST SITE: 2 miles Zuckerberg San Francisco General Hospital and Trauma Center San Francisco,CA

VISITS: Number of visits unavailable

NCT ID: NCT05514054

Imlunestrant Hormone Therapy for Stage I-III ER+, HER2- Breast Cancer

EMBER-4: A Randomized, Open-Label, Phase 3 Study of Adjuvant Imlunestrant vs Standard Adjuvant Endocrine Therapy in Patients Who Have Previously Received 2 to 5 Years of Adjuvant Endocrine Therapy for ER+, HER2- Early Breast Cancer With an Increased Risk of Recurrence Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Imlunestrant (LY3484356), by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Physician's choice of hormone therapy: tamoxifen (Nolvadex®), anastrozole (Arimidex®), letrozole (Femara®), or exemestane (Aromasin®)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Imlunestrant (LY3484356) is an experimental hormone therapy called a SERD (selective estrogen receptor degrader). SERDs work by binding to and breaking down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®) are types of hormone therapy called aromatase inhibitors. Aromatase inhibitors block some production of estrogen that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Tamoxifen (Nolvadex®) is a type of hormone therapy called a selective estrogen receptor modulator (SERM). SERMs work by blocking the activity of estrogen.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05514054' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/oral-serds/' target='_blank'>Metastatic Trial Talk: Oral SERDs for Estrogen Receptor-Positive MBC</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.loxooncology.com/pipeline/ly3484356' target='_blank'>Eli Lilly Drug Information Page: Imlunestrant (LY3484356)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy' target='_blank'>Breastcancer.org: Hormone Therapy</a> </li></ul>

NCT ID: NCT05812807

Pembrolizumab Immunotherapy or Observation to Prevent Recurrence for Stage I-III Triple Negative Breast Cancer

OptimICE-PCR: De-Escalation of Therapy in Early-Stage TNBC Patients Who Achieve pCR After Neoadjuvant Chemotherapy With Checkpoint Inhibitor Therapy Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Observation (no treatment)</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">Immunotherapy may help the body's immune system attack cancer and may reduce the ability of tumor cells to grow and spread.</li> <li class="seamTextUnorderedListItem">Residual disease refers to cancer cells present after treatment.</li> <li class="seamTextUnorderedListItem">A margin that does not contain tumor cells is called a negative margin and tells the surgeon that the tumor has been removed. A positive margin contains tumor cells at or near the edge of the tissue removed.</li> <li class="seamTextUnorderedListItem">In this trial, ER and PR low are defined as 1-10% of cells that are ER or PR positive.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05812807' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li></ul>

VISITS: 1 visit every 1-2 weeks for 5 months

NCT ID: NCT06058377

Chemotherapy with Durvalumab Immunotherapy Before Surgery for Women with Stage II-III HR+, HER2- Breast Cancer

Phase III Trial of Neoadjuvant Durvalumab (NSC 778709) Plus Chemotherapy Versus Chemotherapy Alone for MammaPrint Ultrahigh (MP2) Hormone Receptor (HR) Positive / Human Epidermal Growth Factor Receptor (HER2) Negative Stage II-III Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Mammogram</li> <li class="seamTextUnorderedListItem">MammaPrint testing (if not yet received)</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV, weekly for 3 months</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Doxorubicin (Adriamycin®), by IV, every 2 weeks for 2 months</li> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®), by IV, every 2 weeks 2 months</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Mammogram</li> <li class="seamTextUnorderedListItem">MammaPrint testing (if not yet received)</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV, weekly for 3 months</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®), by IV, monthly for 3 months</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Doxorubicin (Adriamycin®), by IV, every 2 weeks for 2 months</li> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®), by IV, every 2 weeks 2 months</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®), by IV, monthly for 2 months</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), doxorubicin (Adriamycin®), and cyclophosphamide (Cytoxan®) are chemotherapy drugs.</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®) is a type of immunotherapy called a PD-L1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-L1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">A mammogram is a breast cancer screening procedure involving taking an x-ray picture of the breast.</li> <li class="seamTextUnorderedListItem">MammaPrint® is a genetic test that use tumor samples to help guide treatment decisions and determine risk of recurrence (cancer coming back).</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06058377' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/chemotherapy' target='_blank'>Breastcancer.org: Chemotherapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a617030.html#:~:text=Durvalumab%20injection%20is%20in%20a,the%20growth%20of%20cancer%20cells.' target='_blank'>Medline Plus: Durvalumab (Imfinzi®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/screening-testing/mammaprint-test' target='_blank'>Breastcancer.org: MammaPrint Test</a> </li></ul>

NEAREST SITE: 3 miles University of California San Francisco (UCSF) San Francisco,CA

VISITS: 1 visit every week for 3-6 months

NCT ID: NCT01042379

I-SPY 2: Personalized Treatment Before Surgery for Stage II-III Breast Cancer

I-SPY 2 Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups and receive the following before surgery: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Standard of care therapy</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Standard of care therapy</li> <li class="seamTextUnorderedListItem">At least 1 experimental therapy chosen based on your tumor's biomarkers</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">4 MRIs</li> <li class="seamTextUnorderedListItem">2 biopsies</li> <li class="seamTextUnorderedListItem">Blood draws</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Targeted therapy is treatment specific to an individual's tumor type, which are called biomarkers.</li> <li class="seamTextUnorderedListItem">This clinical trial has an adaptive design. This means that experimental drugs will be added during the trial, and experimental drugs that are not more effective than standard of care therapy will be removed.</li> <li class="seamTextUnorderedListItem">At least 80% of people who enroll will receive an experimental drug.</li> <li class="seamTextUnorderedListItem">All drugs will be given before surgery (neoadjuvant therapy). This allows researchers to see how your tumor is responding to the drugs.</li> <li class="seamTextUnorderedListItem">For this trial, cancer is considered high-risk for recurrence if it tests MammaPrint Low (only if your tumor is ER- or ER+, HER2+) or MammaPrint High.</li> <li class="seamTextUnorderedListItem">MammaPrint is a genomic test that identifies genes in your tumor and gives two types of recurrence risk scores: low risk or high risk.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT01042379' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://ispypatient.org/' target='_blank'>Quantum Leap Healthcare Collaborative: I-SPY Patient Website</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/screening-testing/mammaprint-test' target='_blank'>Breastcancer.org: MammaPrint</a> </li><li class='seamTextUnorderedListItem'><a href='https://pubmed.ncbi.nlm.nih.gov/32701140/' target='_blank'>Journal Article: Three-Year Follow-Up Analysis for the I-SPY 2 Adaptively Randomized Clinical Trial</a> </li></ul>

NEAREST SITE: 3 miles University of California San Francisco San Francisco,CA

VISITS: Online surveys

NCT ID: NCT02620852

WISDOM Study: Women Informed to Screen Depending on Measures of Risk

Enabling a Paradigm Shift: A Preference-Tolerant RCT of Personalized vs. Annual Screening for Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups, or you can choose your study group. </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Personalized, Risk-Based Screening</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Screening recommendations based on comprehensive, personal risk assessment</li> <li class="seamTextUnorderedListItem">Saliva sample genetic test</li> <li class="seamTextUnorderedListItem">Online, annual health questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard Annual Screening</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Screening recommendation for annual mammograms</li> <li class="seamTextUnorderedListItem">Online, annual health questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Personalized risk-based screening will take multiple risk factors into consideration, including genetic markers, to determine how often you should have a mammogram.</li> <li class="seamTextUnorderedListItem">This study will help researchers learn if risk-based screening, which helps women learn more about their personal breast cancer risk, is less stressful and as successful at detecting breast cancer as annual screening. </li> <li class="seamTextUnorderedListItem">This study is available in English and Spanish.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02620852' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.thewisdomstudy.org/' target='_blank'>WISDOM: Study Information Page</a> </li></ul>

NEAREST SITE: 3 miles Kaiser Permanente - San Francisco Medical Center San Francisco,CA

VISITS: Coincides with targeted therapy

NCT ID: NCT02693535

Choosing Targeted Therapy Based on a Tumor's Genetic Makeup for Advanced Breast Cancer (TAPUR)

A Basket Study: Targeted Agent and Profiling Utilization Registry (TAPUR) Study Scientific Title

• <p class="seamTextPara"> You will receive an FDA-approved targeted therapy based on your tumor's genetic profile.</p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The targeted therapy you receive will be selected based on your tumor's genetic profile.</li> <li class="seamTextUnorderedListItem">Your treatment may include one or more of the following: Abemaciclib, Futibatinib, Nivolumab, Ipilimumab, Olaparib, Palbociclib, Pembrolizumab, Regorafenib, Sunitinib, Talazoparib, Temsirolimus, Trastuzumab, Pertuzumab, Vemurafenib, Cobimetinib</li> <li class="seamTextUnorderedListItem">This type of study is called a basket trial. Basket trials enroll people based on the kind of mutations found in their tumors.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: ALK, ATM, BRAF, BRAF V600E/D/K/R, BRCA1/2, CDK4, CDK6, CDKN2A, CSF1R, FGFR1/2/3/4, HER2 (ERBB2), high mutational load and others, KIT, MET, MSI-H, mTOR, NRG1, PALB2, PDGFR, POLD1, POLE, RAF-1, RET, ROS1, TSC, VEGFR</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02693535' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.tapur.org/' target='_blank'>ASCO: TAPUR Study Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.net/research-and-advocacy/clinical-trials/what-tapur-study' target='_blank'>Cancer.Net (Video): What is the TAPUR Study?</a> </li><li class='seamTextUnorderedListItem'><a href='https://old-prod.asco.org/research-data/tapur-study/study-participation' target='_blank'>ASCO: TAPUR Study Participation</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.onclive.com/conference-coverage/asco-2016/dr-edward-kim-on-ascos-tapur-trial' target='_blank'>OncLive (Video): About TAPUR</a> </li></ul>

NEAREST SITE: 3 miles University of California, San Francisco San Francisco,CA

VISITS: Number of visits unavailable, over 4 months

NCT ID: NCT02872025

Pembrolizumab Before Surgery for Women With High-Risk DCIS

Testing the Ability of Pembrolizumab to Alter the Tumor Immune MicroEnvironment (TIME) of High Risk DCIS Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">MRI, at diagnosis and right before surgery</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by injection directly into the DCIS, 4 times, with 2 to 4 weeks between each injection</li> <li class="seamTextUnorderedListItem">Surgery (lumpectomy or mastectomy), 1 to 5 weeks after your last injection</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">MRI, at diagnosis and right before surgery</li> <li class="seamTextUnorderedListItem">Tissue collection (biopsy of DCIS)</li> <li class="seamTextUnorderedListItem">Surgery (lumpectomy or mastectomy), within 4 months of diagnosis</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a checkpoint inhibitor. It gets the immune system to go after cancer cells by blocking PD-1. </li> <li class="seamTextUnorderedListItem">It is usually given by IV, but for this study it will be injected directly into the DCIS. </li> <li class="seamTextUnorderedListItem">Giving pembrolizumab (Keytruda®) before surgery allows researchers to study the effects it has on DCIS and the microenvironment (the tissue surrounding the DCIS).</li> <li class="seamTextUnorderedListItem">For this trial, high-risk DCIS means you meet at least 2 of the following: you are younger than 45, the DCIS is palpable (able to be felt by touch), larger than 5 cm, grade II-III, HER2 positive (HER2+), or hormone receptor negative (ER- and PR-).</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02872025' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/symptoms/types/dcis/diagnosis' target='_blank'>Breastcancer.org: Diagnosis of DCIS</a> </li><li class='seamTextUnorderedListItem'><a href='https://ww5.komen.org/BreastCancer/RecommendedTreatmentsforDuctalCarcinomaInSitu.html' target='_blank'>Susan G. Komen: Treatment for DCIS</a> </li><li class='seamTextUnorderedListItem'><a href='https://clinicaltrials.ucsf.edu/trial/NCT02872025' target='_blank'>University of California San Francisco: Study Website</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.bcrf.org/researchers/laura-j-esserman' target='_blank'>BCRF: Laura J. Esserman (Study Researcher)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.keytruda.com/?src=google&med=cpc&camp=Keytruda+Pan+Tumor_Brand_BRND_NA_ENGM_EXCT_TEXT_NA&adgrp=Brand+Keyword_General&kw=keytruda&utm_kxconfid=sq7irm3mh&gclid=Cj0KCQjw6sHzBRCbARIsAF8FMpU1aXb3OCAoZH-Kz-lr_9qfn5S-yKDUnZ6zjvh8GAJBRQ5kuy7Ih0caAlUVE' target='_blank'>Merck Oncology Drug Information Page: Keytruda® (Pembrolizumab)</a> </li></ul>

NEAREST SITE: 3 miles UCSF Breast Care Center San Francisco,CA

NCT ID: NCT03053193

The FLEX Registry: MammaPrint Testing With or Without BluePrint Testing For People With Stage I-III Breast Cancer

MammaPrint, BluePrint, and Full-genome Data Linked With Clinical Data to Evaluate New Gene EXpression Profiles: An Adaptable Registry (FLEX Registry) Scientific Title

• <p class="seamTextPara"> For this data collection registry, you will: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Provide a sample of your tumor (taken during a routine procedure)</li> <li class="seamTextUnorderedListItem">Allow information about your breast cancer treatment to be included in the registry</li> <li class="seamTextUnorderedListItem">Information will be collected from you when you enroll in the registry, during treatment, 1 year after treatment ends; and 2, 5, and 10 years after your diagnosis</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The FLEX Registry will create a database of clinical and genomic information collected from patients who have had their tumor tested with MammaPrint, with or without BluePrint genomic testing. </li> <li class="seamTextUnorderedListItem">MammaPrint is a diagnostic test done on a tumor sample to help guide treatment decisions. The results tell you and your doctor if you have a low or high risk of recurrence. </li> <li class="seamTextUnorderedListItem">BluePrint is a molecular test done on the tumor sample to further classify your risk of recurrence.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03053193' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.agendia.com/clinical-trials/ongoing-studies/' target='_blank'>Trial Sponsor Information Page: FLEX Registry</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/symptoms/diagnosis/genomic_assays' target='_blank'>Breastcancer.org: Tumor Genomic Assay Testing</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/symptoms/testing/types/mammaprint' target='_blank'>Breastcancer.org: MammaPrint Test</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.agendia.com/our-tests/mammaprint/' target='_blank'>Agendia Information Page: MammaPrint Test</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.agendia.com/diagnostic-products/blueprint.html#' target='_blank'>Agendia Information Page: BluePrint Test</a> </li></ul>

NEAREST SITE: 3 miles UCSF Helen Diller Family Comprehensive Cancer Centre San Francisco,CA

VISITS: 21 visits over 2 years

NCT ID: NCT03562637

An Immunotherapy Combination for Stage I-III Triple Negative Breast or ER Low, HER2- Cancer That is Globo H Positive

A Phase III, Randomized, Double-blind, Placebo Controlled Study of Adagloxad Simolenin (OBI 822)/OBI 821 Treatment for High Risk Early Stage Triple Negative Breast Cancer Patients, Defined as Residual Invasive Disease Following Neoadjuvant Chemotherapy OR ≥4 Positive Axillary Nodes Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Adagloxad simolenin (OBI-822) combined with OBI-821, by injection, 21 times over 2 years </li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo, by injection, 21 times over 2 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Adagloxad simolenin (OBI-822) is the investigational immunotherapy used in this study. </li> <li class="seamTextUnorderedListItem">It is given along with the investigational drug OBI-821, which is designed to help stimulate the immune system to fight cancer cells.</li> <li class="seamTextUnorderedListItem">Breast cancer that tests positive for 1%-10% estrogen receptors is called ER-Low.</li> <li class="seamTextUnorderedListItem">This trial is enrolling people with triple negative as well as ER Low breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03562637' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://clinicaltrials.ucsf.edu/trial/NCT03562637' target='_blank'>UCSF Trial Information Page: GLORIA</a> </li><li class='seamTextUnorderedListItem'><a href='https://immuno-oncologynews.com/adagloxad-simolenin/' target='_blank'>Immuno-Oncology News: Adagloxad Simolenin</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/saponin-based-immunoadjuvant-obi-821' target='_blank'>NCI Drug Dictionary: OBI-821</a> </li><li class='seamTextUnorderedListItem'><a href='https://cancerres.aacrjournals.org/content/80/4_Supplement/OT1-08-03' target='_blank'>AACR Abstract: (OBI-822) and OBI-821</a> </li></ul>

NCT ID: NCT03589339

Radiation-Activated NBTXR3 Nanoparticle and Immunotherapy for Metastatic Breast Cancer

A Phase I Study of NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NBTXR3, by intratumoral injection, 1 time</li> <li class="seamTextUnorderedListItem">Stereotaxic ablative radiotherapy</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Nivolumab (Opdivo®) or pembrolizumab (Keytruda®)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NBTXR3 is an experimental nanoparticle designed to kill cancer cells that is activated by stereotaxic ablative radiotherapy.</li> <li class="seamTextUnorderedListItem">NBTXR3 will be injected directly into your tumor.</li> <li class="seamTextUnorderedListItem">Stereotaxic ablative radiotherapy, also called stereotactic radiation or stereotactic radiosurgery, delivers high-dose, precisely-targeted radiation in fewer doses than traditional radiation therapy.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03589339' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.nanobiotix.com/clinical-trials/' target='_blank'>Nanobiotix Drug Information Page: NBTXR3</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mayoclinic.org/tests-procedures/sbrt/pyc-20446794' target='_blank'>Mayo Clinic: Stereotaxic Ablative Radiotherapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy' target='_blank'>Breastcancer.org: Nivolumab (Opdivo®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li></ul>

VISITS: 1 visit every 2 weeks, ongoing

NCT ID: NCT03971409

Avelumab With Binimetinib, Utomilumab, or PF-04518600 For Advanced Triple Negative or ER Low Breast Cancer

Innovative Combination Immunotherapy for Metastatic Triple Negative Breast Cancer (TNBC): A Multicenter, Multi-Arm Translational Breast Cancer Research Consortium Study (InCITe) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 3 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Binimetinib, by mouth, twice daily</li> <li class="seamTextUnorderedListItem">Avelumab (Bavencio®), by IV, every 2 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PF-04518600, by IV, every 2 weeks </li> <li class="seamTextUnorderedListItem">Avelumab (Bavencio®), by IV, every 2 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Utomilumab, by IV, once a month</li> <li class="seamTextUnorderedListItem">Avelumab (Bavencio®), by IV, every 2 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Breast cancer that tests positive for 1%-10% estrogen receptors is called ER Low.</li> <li class="seamTextUnorderedListItem">This trial is enrolling people with triple negative as well as ER Low breast cancer.</li> <li class="seamTextUnorderedListItem">Bavencio is type of immunotherapy called a PD-L1 inhibitor. It has been approved to treat certain types of cancer. Its use in breast cancer is considered experimental. </li> <li class="seamTextUnorderedListItem">Binimetinib (Mektovi®) is targeted therapy that blocks MEK, which helps cancer cells grow. It is used to treat metastatic melanoma. Its use in breast cancer is considered experimental.</li> <li class="seamTextUnorderedListItem">PF-04518600 is an investigational immunotherapy that targets OX40, a protein found on immune cells that have interacted with cancer cells. </li> <li class="seamTextUnorderedListItem">Utomilumab is an investigational immunotherapy that targets the 4-1BB (CD-137) protein on certain immune cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03971409' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/avelumab' target='_blank'>NCI Drug Dictionary: Avelumab</a> </li><li class='seamTextUnorderedListItem'><a href='https://immuno-oncologynews.com/pf-04518600/' target='_blank'>Immuno-Oncology News: PF-04518600</a> </li><li class='seamTextUnorderedListItem'><a href='https://pfe-pfizercom-prod.s3.amazonaws.com/news/asco/Pfizer_IO_41BB_UtomilumabFactSheet.pdf' target='_blank'>Pfizer Oncology Information Page: Utomilumab</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/about-cancer/treatment/drugs/binimetinib' target='_blank'>NCI Drug Dictionary: Binimetinib</a> </li></ul>

NEAREST SITE: 3 miles UCSF Medical Center-Mission Bay/Benioff Children's Hospital San Francisco,CA

NCT ID: NCT03990896

Talazoparib in Women With Metastatic Triple Negative or HR+, HER2- Breast Cancer with a Tumor (Not Inherited) BRCA1/2 Mutation

Evaluation of Talazoparib, a PARP Inhibitor, in Patients With Somatic BRCA Mutant Metastatic Breast Cancer: Genotyping Based Clinical Trial Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Talazoparib (Talzenna®), by mouth, daily, ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Talazoparib (Talzenna®) is a type of targeted therapy called a PARP inhibitor. It prevents the PARP protein from repairing damaged DNA in tumor cells.</li> <li class="seamTextUnorderedListItem">BRCA1/2 mutations are called germline when they are inherited. </li> <li class="seamTextUnorderedListItem">BRCA1/2 mutations are called somatic when they are not inherited.</li> <li class="seamTextUnorderedListItem">Targets or mutations: BRCA 1 (tumor), BRCA 2 (tumor)</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03990896' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-terms/def/somatic-mutation' target='_blank'>NCI Drug Dictionary: Somatic Mutation</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.talzenna.com/?source=google&HBX_PK=s_talazoparib&skwid=43700039109817433' target='_blank'>Pfizer Oncology: Talzenna®</a> </li><li class='seamTextUnorderedListItem'><a href='https://blog.dana-farber.org/insight/2016/07/how-do-parp-inhibitors-work-in-cancer/' target='_blank'>Dana-Farber Cancer Institue: How Do PARP Inhibitors Work In Cancer? (Video)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.onclive.com/publications/oncology-live/2017/vol-18-no-13/blurring-the-lines-between-germline-and-somatic-mutations-in-cancer' target='_blank'>OncLive: Blurring the Lines Between Germline and Somatic Mutations in Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.nature.com/articles/s41416-018-0127-5' target='_blank'>Journal Article: BRCA1/2 Testing: Therapeutic Implications for Breast Cancer Management</a> </li></ul>

NEAREST SITE: 3 miles Univ. of Cali. San Francisco Medical Center San Francisco,CA

VISITS: 1 visit every 3 weeks

NCT ID: NCT04042701

Trastuzumab Deruxtecan ADC and Pembrolizumab Immunotherapy for Advanced HER2 Positive and HER2 Low Breast Cancer

A Phase 1b, Multicenter, Two-Part, Open-Label Study of Trastuzumab Deruxtecan (DS-8201a), An Anti-Human Epidermal Growth Factor Receptor-2 (HER2)-Antibody Drug Conjugate (ADC), In Combination With Pembrolizumab, An Anti-PD-1 Antibody, In Subjects With Locally Advanced/Metastatic Breast Or Non-Small Cell Lung Cancer (NSCLC) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (Enhertu®), by IV, every 3 weeks</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">HER2 low expression is defined as IHC 1+ or 2+ and ISH-.</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (Enhertu®) is an antibody-drug conjugate (ADC). It targets HER2 to deliver a chemotherapy directly to the cancer cells. It is approved for use to treat people with metastatic HER2+ breast cancer who have already received two anti-HER2 therapies. Its use in this trial is considered experimental.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor.</li> <li class="seamTextUnorderedListItem">Blocking PD-1 allows the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This study is also enrolling patients with other types of solid tumors.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04042701' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2-positive-breast-cancer' target='_blank'>FDA: FDA Approves Fam-Trastuzumab Deruxtecan-nxki</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-terms/def/fam-trastuzumab-deruxtecan' target='_blank'>NCI Drug Dictionary: Fam-Trastuzumab Deruxtecan</a> </li><li class='seamTextUnorderedListItem'><a href='https://ascopost.com/news/february-2020/trastuzumab-deruxtecan-in-her2-low-expressing-previously-treated-advanced-breast-cancer/' target='_blank'>ASCO Post: Trastuzumab Deruxtecan in HER2–Low-Expressing, Previously Treated Advanced Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda)</a> </li></ul>

PHASE: I-II

NCT ID: NCT04143711

Immunotherapy DF1001 Alone or With Keytruda® for IHC HER2 1+, 2+ or 3+ Metastatic Breast Cancer

A Phase I/II, First-In-Human, Multi-Part, Open-Label, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of DF1001 in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DF1001 immunotherapy</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">You may also receive:</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DF1001 is an experimental immunotherapy. </li> <li class="seamTextUnorderedListItem">Keytruda® is a type of immunotherapy called a PD-L1 inhibitor. It is approved to treat certain types of cancers. Its use in breast cancer is considered experimental.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04143711' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.keytruda.com/msi-h/' target='_blank'>Merck Oncology Information Page: Keytruda® (Pembrolizumab)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.dragonflytx.com/copy-of-about-us-1' target='_blank'>Dragonfly Therapeutics Information Page: DF1001</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554437/' target='_blank'>Journal Article: Cancer Immunotherapy Based on Natural Killer Cells: Current Progress and New Opportunities</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.curetoday.com/articles/keytruda-approved-for-microsatellite-instability-high-and-mismatch-repair-deficient-cancers' target='_blank'>Cure Today: Keytruda Approved for Any Solid Tumor With a Specific Genetic Marker</a> </li></ul>

NEAREST SITE: 3 miles Curebase San Francisco,CA

NCT ID: NCT04510129

Collecting Tumor Samples to Develop a Test to Predict Response to Treatment

Predicting Immunotherapy Efficacy From Analysis of Pre-treatment Tumor Biopsies Scientific Title

• <p class="seamTextPara"> You will provide the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Tumor samples</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">OncoPrism™ is a test that helps providers predict response to immunotherapy.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04510129' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://cofactorgenomics.com/technology/' target='_blank'>Cofactor Genomics: OncoPrism™ Test</a> </li></ul>

NEAREST SITE: 3 miles UCSF Medical Center at Mission Bay San Francisco,CA

NCT ID: NCT04606446

Experimental Therapy PF-07248144 for Advanced ER+, HER2- Breast Cancer

A Phase 1 Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetic, Pharmacodynamic, and Anti-tumor Activity of PF-07248144 in Participants With Advanced or Metastatic Solid Tumors. Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 3 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PF-07248144, ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PF-07248144, ongoing</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PF-07248144, ongoing</li> <li class="seamTextUnorderedListItem">Letrozole (Femara®), by mouth, daily, ongoing</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), by mouth, daily (3 weeks on, 1 week off), ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PF-07248144 is a KAT6 Inhibitor</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a hormone therapy approved to treat postmenopausal women with advanced breast cancer.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor degrader (SERD).</li> <li class="seamTextUnorderedListItem">Letrozole (Femara®) is a type of hormone therapy called an aromatase inhibitor. It is commonly used to treat hormone-sensitive breast cancer.</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®) is commonly used with anti-estrogen therapy for metastatic, hormone-positive (ER+ and/or PR+), HER2-negative (HER2-) breast cancer, but its use in this trial is considered experimental.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04606446' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.pfizerclinicaltrials.com/find-a-trial/nct04606446' target='_blank'>Pfizer Trial Information Page: PF-07248144</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/update-on-hormone-receptor-positive-mbc-2021/' target='_blank'>Metastatic Trial Talk: Update on Hormone Receptor-Positive MBC</a> </li></ul>

NEAREST SITE: 3 miles University of California, San Francisco (UCSF) San Francisco,CA

NCT ID: NCT04802759

Experimental Anti-Estrogen Therapy Alone or with Targeted Therapy or Chemotherapy for Women with Advanced ER+, HER2- Breast Cancer

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Breast Cancer (MORPHEUS- BREAST CANCER) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 6 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Giredestrant, by mouth, daily, ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Giredestrant, by mouth, daily, ongoing</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, twice daily, ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Giredestrant, by mouth, daily, ongoing</li> <li class="seamTextUnorderedListItem">Ipatasertib, by mouth, daily (3 weeks on, 1 week off), ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 4</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Giredestrant, by mouth, daily, ongoing</li> <li class="seamTextUnorderedListItem">Inavolisib, by mouth, daily, ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 5</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Giredestrant, by mouth, daily, ongoing</li> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®), by mouth, daily (3 weeks on, 1 week off), ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 6</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Giredestrant, by mouth, daily, ongoing</li> <li class="seamTextUnorderedListItem">Everolimus (Afinitor®), by mouth, daily, ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Giredestrant is an experimental anti-estrogen therapy you take by mouth. It is a type of anti-estrogen therapy called a SERD (selective estrogen receptor degrader).</li> <li class="seamTextUnorderedListItem">SERDs work by binding to and breaking down estrogen receptors. The only SERD currently approved to treat breast cancer is fulvestrant (Faslodex®). Faslodex is given by injection. </li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®) is a type of targeted therapy called a CDK 4/6 inhibitor -- it blocks two enzymes, CDK4 and CDK6, that help cancer grow. It is already approved to treat some metastatic breast cancer, but its use in this trial is experimental.</li> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®) is also a CDK 4/6 inhibitor. It is already approved to treat some metastatic breast cancer, but its use in this trial is experimental.</li> <li class="seamTextUnorderedListItem">Ipatasertib is an experimental type of targeted therapy called an AKT inhibitor. It may slow or stop cancer cells from growing by blocking the enzyme (protein) AKT. </li> <li class="seamTextUnorderedListItem">Inavolisib is an experimental type of targeted therapy called a PI3K inhibitor. If there is a mutation in the PIK3CA gene, the PI3K pathway can become overactivated, allowing cancer cells to grow. Inavolisib may slow or stop cancer cells from growing by blocking this pathway. </li> <li class="seamTextUnorderedListItem">Everolimus (Afinitor®) is a type of targeted therapy called an mTOR inhibitor. It works by interfering with a cancer cell's ability to divide and grow.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04802759' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.genentechoncology.com/pipeline-molecules/serd-3.html' target='_blank'>Genentech Drug Information Page: Giredestrant (GDC-9545)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted_therapies/cdk46-inhibitors' target='_blank'>Breastcancer.org: CDK 4/6 Inhibitors (Abemaciclib & Ribociclib)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.genentechoncology.com/pipeline-molecules/ipatasertib.html' target='_blank'>Genentech Drug Information Page: Ipatasertib (AKT Inhibitor)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.genentechoncology.com/pipeline-molecules/inavolisib.html' target='_blank'>Genentech Drug Information Page: Inavolisib (P13K Alpha Inhibitor)</a> </li><li class='seamTextUnorderedListItem'><a href='http://chemocare.com/chemotherapy/drug-info/everolimus.aspx' target='_blank'>Chemocare: Everolimus (Afinitor)</a> </li></ul>

VISITS: 2 visits

NCT ID: NCT04821141

Bazedoxifene and Estrogen Hormone Therapy to Reduce Risk Factors for Developing Breast Cancer

Randomized IIB Study of the Effect of Bazedoxifene Plus Conjugated Estrogens on Breast Imaging and Tissue Biomarkers in Peri or Post-Menopausal Women at Increased Risk for Development of Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Bazedoxifene, by mouth, daily for 6 months</li> <li class="seamTextUnorderedListItem">Estrogen, by mouth, daily for 6 months</li> <li class="seamTextUnorderedListItem">Mammogram, 2 times within 6 months</li> <li class="seamTextUnorderedListItem">Fine needle aspiration biopsy, 2 times within 6 months</li> <li class="seamTextUnorderedListItem">Blood tests, 2 times within 6 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Mammogram, 2 times within 6 months</li> <li class="seamTextUnorderedListItem">Fine needle aspiration biopsy, 2 times within 6 months</li> <li class="seamTextUnorderedListItem">Blood tests, 2 times within 6 months</li> </ul> <p class="seamTextPara"> followed 6 months later by (optional): </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Bazedoxifene, by mouth, daily for 6 months</li> <li class="seamTextUnorderedListItem">Estrogen, by mouth, daily for 6 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Bazedoxifene is a type of hormone therapy called a selective estrogen receptor modulator (SERM). SERMs work by blocking the activity of estrogen. It may help reduce the risk of breast cancer.</li> <li class="seamTextUnorderedListItem">Estrogen is a hormone used to treat women experiencing hot flashes.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04821141' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2022-03864&r=1#:~:text=Giving%20bazedoxifene%20with%20conjugated%20estrogens,increased%20risk%20for%20breast%20cancer.' target='_blank'>National Cancer Institute: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a614004.html' target='_blank'>Medline Plus: Bazedoxifene and Estrogen</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cdc.gov/cancer/breast/basic_info/mammograms.htm' target='_blank'>Centers for Disease Control and Prevention: Mammogram</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.org/cancer/breast-cancer/screening-tests-and-early-detection/breast-biopsy/fine-needle-aspiration-biopsy-of-the-breast.html#:~:text=During%20a%20fine%20needle%20aspiration,needle%20biopsy%20is%20often%20preferred).' target='_blank'>American Cancer Society: Fine Needle Aspiration Biopsy</a> </li></ul>

NEAREST SITE: 3 miles Research Site San Francisco,CA

VISITS: 1 visit every month, ongoing

NCT ID: NCT04829604

Antibody-Drug Conjugate ARX788 for Metastatic HER2 Positive Breast Cancer

A Global, Phase 2 Study of ARX788 in HER2-positive, Metastatic Breast Cancer Patients Whose Disease is Resistant or Refractory to T-DM-1 or T-DXd, and/or Tucatinib-containing Regimens Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ARX788, by IV, once a month, ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Antibody-drug conjugates (ADCs) are therapies that contain an antibody linked to a specific type of chemotherapy. They are designed to deliver high doses of chemotherapy to cancer cells while sparing normal cells. </li> <li class="seamTextUnorderedListItem">ARX788 is an investigational antibody-drug conjugate -- this means it is only available in clinical trials. </li> <li class="seamTextUnorderedListItem">ARX788 targets HER2 to deliver the chemotherapy AS269 directly to cancer cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04829604' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Getting to the Target, Antibody Drug Conjugates</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.onclive.com/view/fda-grants-fast-track-status-to-adc-arx788-for-her2-metastatic-breast-cancer' target='_blank'>OncLive: FDA Grants Fast Track Status to ADC ARX788 for HER2+ Metastatic Breast Cancer</a> </li></ul>

NEAREST SITE: 3 miles California Pacific Medical Center-Pacific Campus San Francisco,CA

NCT ID: NCT04852887

Hormone Therapy Alone or With Radiation for Stage I HR+, HER2- Breast Cancer

A Phase III Clinical Trial Evaluating De-Escalation of Breast Radiation for Conservative Treatment of Stage I, Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Hormone Therapy and Radiation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Physician's choice of hormone therapy: tamoxifen (Nolvadex®), anastrozole (Arimidex®), letrozole (Femara®), or exemestane (Aromasin®), daily, at least 5 years</li> <li class="seamTextUnorderedListItem">Radiation</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Hormone Therapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Physician's choice of hormone therapy: tamoxifen (Nolvadex®), anastrozole (Arimidex®), letrozole (Femara®), or exemestane (Aromasin®), daily, at least 5 years</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®) are types of hormone therapy called aromatase inhibitors. Aromatase inhibitors block some production of estrogen that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Tamoxifen (Nolvadex®) is a type of hormone therapy called a selective estrogen receptor modulator (SERM). SERMs work by blocking the activity of estrogen.</li> <li class="seamTextUnorderedListItem">Radiation therapy uses high-energy x-rays to damage cancer cell DNA. These x-rays stop cancer cells from dividing and growing, thus slowing or stopping tumor growth.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04852887' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.nrgoncology.org/Home/News/Post/NRG-BR007-The-DEBRA-Trial' target='_blank'>NRG Oncology: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/radiation-therapy' target='_blank'>Breastcancer.org: Radiation Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy' target='_blank'>Breastcancer.org: Hormone Therapy</a> </li></ul>

VISITS: 1 visit per month, ongoing

NCT ID: NCT04862663

Capivasertib, Palbociclib, and Fulvestrant for Advanced ER+, HER2- Breast Cancer

A Phase Ib/III Randomised Study of Capivasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Capivasertib, by mouth, daily (4 days on, 3 days off), ongoing</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), by mouth, daily (3 weeks on, 1 week off), ongoing</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, once a month</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Capivasertib is a targeted therapy that blocks the Akt protein. The Akt protein helps cancer cells divide and grow.</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®) is a type of targeted therapy called a CDK4/6 inhibitor. It is approved for treating metastatic hormone-positive, HER2-negative breast cancer.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a hormone therapy approved to treat postmenopausal women with advanced breast cancer.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor degrader (SERD).</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04862663' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/capivasertib?redirect=true' target='_blank'>NCI Drug Dictionary: Capivasertib</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30857-5/fulltext' target='_blank'>Journal Article: Capivasertib Inhibits a Key Pathway in Metastatic Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a615013.html' target='_blank'>Medline Plus: Palbociclib</a> </li><li class='seamTextUnorderedListItem'><a href='https://en.wikipedia.org/wiki/Fulvestrant' target='_blank'>Wikipedia: Fulvestrant</a> </li></ul>

NEAREST SITE: 3 miles UCSF Helen Diller Family Comprehensive Cancer Center San Francisco,CA

VISITS: 1 visit every 3 weeks, for 1 year

NCT ID: NCT04893109

Trastuzumab by Injection with Chemotherapy or an Antibody-Drug Conjugate for Stage I HER2 Positive Breast Cancer

A Randomized Phase II Trial of Adjuvant Trastuzumab Emtansine (T-DM1) Followed by Subcutaneous Trastuzumab Versus Paclitaxel in Combination With Subcutaneous Trastuzumab for Stage I HER2-positive Breast Cancer (ATEMPT 2.0) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab emtansine/T-DM1 (Kadcyla®), by IV, every 3 weeks, for 4.5 months</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®)/Herceptin Hylecta, by injection, every 3 weeks, for 7.5 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV, every week, for 3 months</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®)/Herceptin Hylecta, by injection, every 3 weeks, for 11.5 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab emtansine/T-DM1 (Kadcyla®) is an antibody-drug conjugate (ADC). It uses an antibody -— the HER2-targeted therapy trastuzumab (Herceptin®) -— to deliver the chemotherapy DM1 directly to the cancer cells.</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®) is an anti-HER2 targeted therapy commonly used to treat HER2 positive breast cancer. </li> <li class="seamTextUnorderedListItem">Herceptin Hylecta is a form of trastuzumab that is given by injection instead of by IV. </li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®) is a chemotherapy routinely used to treat breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04893109' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-new-formulation-herceptin-subcutaneous-use' target='_blank'>FDA Drug Approvals and Database: FDA Approves New Formulation of Herceptin for subcutaneous Use</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted_therapies/kadcyla' target='_blank'>Breastcancer.org: Trastuzumab Emtansine/T-DM1 (Kadcyla®)</a> </li></ul>

VISITS: Coincides with surgery

NCT ID: NCT05020574

Impact of Antibiotics on Infection and the Microbiome in People Receiving a Mastectomy

Microbiome and Association With Implant Infections: Investigating the Impact of Antibiotics on the Gut and Breast Microbiomes Post-mastectomy With Implant-based Breast Reconstruction Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cephalexin (Keflex®) antibiotic, before and during surgery</li> <li class="seamTextUnorderedListItem">Cephalexin (Keflex®) antibiotic, daily for at least 7 days after surgery</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cephalexin (Keflex®) antibiotic, before and during surgery</li> <li class="seamTextUnorderedListItem">No antibiotics after surgery (unless infection occurs)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">A mastectomy is surgery to remove a breast.</li> <li class="seamTextUnorderedListItem">Women with a strong family history of breast cancer or a BRCA mutation may choose to undergo a mastectomy to reduce their risk of developing breast cancer.</li> <li class="seamTextUnorderedListItem">Cephalexin (Keflex®) is an antibiotic used to prevent infection after surgery.</li> <li class="seamTextUnorderedListItem">The microbiome consists of the many bacteria, viruses, and fungi found on your body.</li> <li class="seamTextUnorderedListItem">The harmful bacteria cause disease such as infection, and the beneficial bacteria help keep you healthy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05020574' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/surgery/mastectomy' target='_blank'>Breastcancer.org: Mastectomy</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a682733.html' target='_blank'>MedlinePlus: Cephalexin (Keflex®)</a> </li></ul>

NCT ID: NCT05056077

Tools to Improve Nutrition and Physical Activity After Treatment for People with Stage I-III Breast Cancer

Optimizing Intervention Tools to Improve Nutrition and Physical Activity for Cancer Survivors (Tools To Be Fit) (TTBF) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to receive 1 or more of the following 4 tools: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">A report comparing your nutrition and physical activity to American Cancer Society guidelines and a nutrition and physical activity booklet for people with a history of cancer</li> <li class="seamTextUnorderedListItem">Receive text messages and use a digital health tool kit, 1 year</li> <li class="seamTextUnorderedListItem">Health coaching sessions, 30-45 minutes each, 15 times within 1 year</li> <li class="seamTextUnorderedListItem">Support coaching sessions, 30-45 minutes each, 4 times within 1 year</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">People with a history of cancer whose nutrition and physical activity habits are consistent with the American Cancer Society's guidelines may live longer without cancer coming back (recurrence).</li> <li class="seamTextUnorderedListItem">The four components of the program being studied may help people with a history of cancer adopt recommended health behaviors after they have completed treatment.</li> <li class="seamTextUnorderedListItem">A support person of your choice will also participate in this study.</li> <li class="seamTextUnorderedListItem">This trial is enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">This trial is also available in Spanish.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05056077' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NCT ID: NCT05086692

MDNA11 Immunotherapy for Advanced Triple Negative Breast Cancer

A Phase 1/2 Open Label, Dose Escalation and Expansion Study of MDNA11, IL-2 Superkine, Administered Alone or in Combination With Immune Checkpoint Inhibitor in Patients With Advanced Solid Tumors (ABILITY) Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups based on when you enroll: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">MDNA11, by IV, every 2 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">MDNA11, by IV, every 2 weeks</li> <li class="seamTextUnorderedListItem">Checkpoint inhibitor as determined by your physician</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">MDNA11 is an experimental immunotherapy called interleukin-2 (IL-2).</li> <li class="seamTextUnorderedListItem">IL-2 activates immune cells to kill cancer cells.</li> <li class="seamTextUnorderedListItem">A checkpoint inhibitor is a type of immunotherapy. It gets the immune system to go after cancer cells by blocking the protein PD-1.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05086692' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.medicenna.com/pipeline/mdna11/' target='_blank'>Medicenna Drug Information Page: MDNA11</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.globenewswire.com/news-release/2021/12/22/2356750/0/en/Medicenna-Announces-Preliminary-Clinical-Data-Showing-Preferential-Stimulation-of-Anti-Cancer-Immune-Cells-with-MDNA11-Treatment-in-the-Phase-1-2-ABILITY-Study.html' target='_blank'>Medicenna Press Release: MDNA11 Treatment in the Phase 1/2 ABILITY Study</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy#section-cytokines' target='_blank'>Breastcancer.org: Interleukin-2</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy#section-immune-checkpoint-inhibitors' target='_blank'>Breastcancer.org: Checkpoint Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/immunotherapy/types/checkpoint-inhibitors' target='_blank'>Cancer Research UK: Checkpoint Inhibitors</a> </li></ul>

NCT ID: NCT05107674

A Study of NX-1607 in Adults With Advanced Malignancies

A Phase 1a, Dose Escalation, Safety and Tolerability Study of NX-1607, a Casitas B-lineage Lymphoma Proto-oncogene (CBL-B) Inhibitor, in Adults With Advanced Malignancies, With Phase 1b Expansion in Select Tumor Types Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NX-1607, by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NX-1607 is an experimental immunotherapy called a CBL-B inhibitor that stimulates the immune system to go after and kill cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05107674' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.nurixtx.com/pipeline/' target='_blank'>Nurix Therapeutics: NX-1607 Drug Information Page</a> </li></ul>

NEAREST SITE: 3 miles University of California, San Francisco Helen Diller Family Cancer Center San Francisco,CA

VISITS: 1 visit every month for 6 months, then every 6 months for 2.5 years

NCT ID: NCT05232916

GLSI-100 Immunotherapy for HER2 Positive Breast Cancer

A Randomized, Multicenter, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of HER2/Neu Peptide GLSI-100 (GP2 + GM-CSF) in HER2/Neu Positive Subjects With Residual Disease or High-Risk PCR After Both Neoadjuvant and Postoperative Adjuvant Trastuzumab-based Therapy (FLAMINGO-01) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">GLSI-100, by injection, monthly for 6 months, then every 6 months for 2.5 years</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for GLSI-100, by injection, monthly for 6 months, then every 6 months for 2.5 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">GLSI-100 is an experimental immunotherapy that targets HER2 positive cells.</li> <li class="seamTextUnorderedListItem">GLSI-100 has two components called GP2 and GM-CSF.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05232916' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://greenwichlifesciences.com/technology/gp2-cancer-immunotherapy/' target='_blank'>Greenwich LifeSciences: GP2 Drug Information Page</a> </li></ul>

VISITS: May require hospitalization

NCT ID: NCT05239143

P-MUC1C-ALLO1 CAR-T Cell Immunotherapy for Advanced Breast Cancer

A Phase 1 Dose Escalation and Expanded Cohort Study of P-MUC1C-ALLO1 in Adult Subjects With Advanced or Metastatic Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups based on when you enroll: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">P-MUC1C-ALLO1 CAR-T cell immunotherapy, by IV, 1 session</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">P-MUC1C-ALLO1 CAR-T cell immunotherapy, by IV, multiple sessions</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">May require 1 biopsy</li> <li class="seamTextUnorderedListItem">Rimiducid (CaspaCIDe®) may be given for safety</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule.</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">P-MUC1C-ALLO1 is an experimental immunotherapy called CAR-T cell therapy.</li> <li class="seamTextUnorderedListItem">Allogeneic CAR-T cell therapy is an immunotherapy made from donor immune cells.</li> <li class="seamTextUnorderedListItem">Donor immune cells are modified with chimeric antigen receptors (CARs) so they can attack cancer cells.</li> <li class="seamTextUnorderedListItem">The CAR T-cells are then infused back into you while you are hospitalized.</li> <li class="seamTextUnorderedListItem">Rimiducid (CaspaCIDe®) is an enzyme that can be administered for safety to kill CAR-T cells, if needed.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05239143' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://poseida.com/science/pipeline/#cart-therapies' target='_blank'>Poseida Therapeutics Drug Information Page: P-MUC1C-ALLO1</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.prnewswire.com/news-releases/poseida-therapeutics-announces-fda-clearance-of-investigational-new-drug-application-for-p-muc1c-allo1-a-fully-allogeneic-car-t-targeting-multiple-solid-tumors-301447910.html' target='_blank'>Poseida Therapeutics Press Release: P-MUC1C-ALLO1</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.bellicum.com/caspacide-safety-switch/' target='_blank'>Bellicum Phamaceuticals Drug Information Page: Rimiducid (CaspaCIDe®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.frontiersin.org/articles/10.3389/fimmu.2020.618427/full' target='_blank'>Journal Article: Allogeneic CAR T-Cell Immunotherapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/from-the-experts/what-is-car-t-therapy/' target='_blank'>Metastatic Trial Talk: What is CAR-T Therapy?</a> </li></ul>

NCT ID: NCT05252416

BLU-222 Targeted Therapy and Hormone Therapy for Advanced ER+, HER2- Breast Cancer

A Phase 1/2 Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of BLU-222 as a Single Agent and in Combination Therapy for Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BLU-222, by mouth</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BLU-222 is an experimental targeted therapy called a CDK 2 inhibitor. It may block an enzyme, CDK 2, that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor downregulator (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05252416' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.blueprintmedicines.com/pipeline/' target='_blank'>Blueprint Medicines Corporation: BLU-222 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li></ul>

NEAREST SITE: 3 miles GSK Investigational Site San Francisco,CA

NCT ID: NCT05277051

GSK4381562 Immunotherapy for Advanced Breast Cancer

A Phase 1 First-Time-in-Human, Open-Label Study of GSK4381562 Administered as Monotherapy and in Combination With Anticancer Agents in Participants With Selected Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups based on when you enroll: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">GSK4381562 (SRF813)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">GSK4381562 (SRF813)</li> <li class="seamTextUnorderedListItem">Dostarlimab (Jemperli®), by IV</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">GSK4381562 (SRF813) is an experimental immunotherapy that targets PVRIG/SRF813 to activate immune cells to fight cancer cells.</li> <li class="seamTextUnorderedListItem">Dostarlimab (Jemperli®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05277051' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://investors.surfaceoncology.com/news-releases/news-release-details/surface-oncology-achieves-30-million-milestone-first-patient' target='_blank'>Surface Oncology Press Release: First Patient Dosed with GSK4381562 (SRF813)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/jemperli' target='_blank'>Breastcancer.org: Dostarlimab (Jemperli®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy' target='_blank'>Breastcancer.org: Immunotherapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy#section-immune-checkpoint-inhibitors' target='_blank'>Breastcancer.org: Immune Checkpoint Inhibitors</a> </li></ul>

NEAREST SITE: 3 miles UCSF San Francisco,CA

NCT ID: NCT05307705

LOXO-783 Targeted Therapy for Advanced Breast Cancer with a PIK3CA Mutation

A Study of LOXO-783 Administered as Monotherapy and in Combination With Anticancer Therapies for Patients With Advanced Breast Cancer and Other Solid Tumors With a PIK3CA H1047R Mutation Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 6 groups based on when you enroll: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: LOXO-783 Alone at Different Doses</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LOXO-783, by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: LOXO-783 with Hormone Therapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LOXO-783, by mouth</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection or imlunestrant, by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3: LOXO-783 with Targeted Therapy and Hormone Therapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LOXO-783, by mouth</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth</li> <li class="seamTextUnorderedListItem">Physician's choice of aromatase inhibitor, by mouth or fulvestrant (Faslodex®), by injection or imlunestrant, by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 4: LOXO-783 with Hormone Therapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LOXO-783, by mouth</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 5: LOXO-783 with Chemotherapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LOXO-783, by mouth</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 6: LOXO-783 Alone</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LOXO-783, by mouth</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LOXO-783 is an experimental targeted therapy called a PI3Kα inhibitor. If there is a mutation in the PIK3CA gene, the PI3K pathway can become overactivated which allows cancer cells to grow. LOXO-783 may block the PI3K pathway.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) and imlunestrant are hormone therapies called selective estrogen receptor degraders (SERDs). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is approved, and imlunestrant is experimental.</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®) is a targeted therapy called a CDK 4/6 inhibitor. CDK 4/6 inhibitors block two enzymes that help cancer grow.</li> <li class="seamTextUnorderedListItem">If you are in Group 2, you will receive anastrozole (Arimidex®), exemestane (Aromasin®), or letrozole (Femara®).</li> <li class="seamTextUnorderedListItem">Aromatase inhibitors are hormone therapies that block some production of estrogen that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®) is a chemotherapy drug.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: PIK3CA</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05307705' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.loxooncology.com/pipeline' target='_blank'>Loxo Oncology/ Eli Lilly Drug Information Page: LOXO-783 and Imlunestrant</a> </li><li class='seamTextUnorderedListItem'><a href='https://finance.yahoo.com/news/loxo-oncology-lilly-announces-details-130000189.html' target='_blank'>Eli Lilly Press Release: LOXO-783</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.newswire.ca/news-releases/lilly-announces-new-clinical-data-from-verzenio-and-oral-serd-programs-at-the-american-society-of-clinical-oncology-annual-meeting-859069920.html' target='_blank'>Eli Lilly Press Release: Imlunestrant</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy' target='_blank'>Breastcancer.org: Hormone Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/taxol' target='_blank'>Breastcancer.org: Paclitaxel (Taxol®)</a> </li></ul>

NCT ID: NCT05417594

AZD9574 Targeted Therapy for Advanced HER2 Negative Breast Cancer With Certain Mutations

A Modular Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (CERTIS1) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">AZD9574, by mouth</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">AZD9574 is an experimental targeted therapy called a PARP inhibitor. PARP inhibitors stop the growth of cancer cells by blocking enzymes called poly ADP ribose polymerase (PARP).</li> <li class="seamTextUnorderedListItem">This trial is enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">The mutations can be inherited (also called germline) or in a tumor (also called somatic).</li> <li class="seamTextUnorderedListItem">Targets or mutations: BRCA1, BRCA2, PALB2, RAD51C, RAD51D</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05417594' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://aacrjournals.org/cancerres/article/82/12_Supplement/2609/702588' target='_blank'>Abstract: AZD9574</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.komen.org/breast-cancer/treatment/type/parp-inhibitors/' target='_blank'>Susan G. Komen: PARP Inhibitors</a> </li></ul>

NCT ID: NCT05456373

Device to Detect Positive Margins During Lumpectomy

Intraoperative Use of ClearEdge Device in Breast Conserving Surgery Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Standard of care assessment of margins during surgery</li> <li class="seamTextUnorderedListItem">ClearEdge tissue imaging device</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Standard of care assessment of margins during surgery</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The ClearEdge tissue imaging device uses a new technology to help the surgeon detect tissue abnormalities during surgery and identify cancer cells that would have been left behind (positive margins).</li> <li class="seamTextUnorderedListItem">This may allow the surgeon to remove all cancer cells during surgery and avoid cancer recurrence or the need to repeat surgery.</li> <li class="seamTextUnorderedListItem">A lumpectomy is sometimes called a partial mastectomy. It is a standard of care (routine) procedure that removes the tumor and a rim of surrounding normal tissue (margins) while leaving as much normal breast tissue as possible.</li> <li class="seamTextUnorderedListItem">A margin that does not contain tumor cells is called a negative margin and tells the surgeon that the tumor has been removed. A positive margin contains tumor cells at or near the edge of the tissue removed.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05456373' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/surgery/lumpectomy' target='_blank'>Breastcancer.org: Lumpectomy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-terms/def/margin' target='_blank'>National Cancer Institute: Clear Margins</a> </li><li class='seamTextUnorderedListItem'><a href='https://lsbiopath.com/patient/' target='_blank'>LSBiopath: ClearEdge Device Information Page</a> </li></ul>

NEAREST SITE: 3 miles University of California San Francisco Health San Francisco,CA

NCT ID: NCT05508906

OP-1250 Hormone Therapy with Targeted Therapy for Advanced HR+, HER2- Breast Cancer

A Phase 1b Open-Label Multicenter Study of OP-1250 in Combination With the CDK4/6 Inhibitor Ribociclib or With the PI3K Inhibitor Alpelisib in Adult Subjects With Advanced and/or Metastatic HR Positive, HER2 Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">OP-1250</li> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">OP-1250</li> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">OP-1250 is an experimental hormone therapy called a selective estrogen receptor downregulator (SERD) and complete estrogen receptor antagonist (CERAN). SERDs bind to and break down estrogen receptors, and CERANs block estrogen receptors.</li> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®) is a type of targeted therapy called a CDK 4/6 inhibitor. CDK 4/6 inhibitors block two enzymes, CDK4 and CDK6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®) is a type of targeted therapy called a PI3K inhibitor. Blocking the PI3K pathway may slow or stop cancer cells from growing.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05508906' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://olema.com/science/' target='_blank'>Olema Oncology Drug Information Page: OP-1250</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/kisqali' target='_blank'>Breastcancer.org: Ribociclib (Kisqali®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/piqray' target='_blank'>Breastcancer.org: Alpelisib (Piqray®)</a> </li></ul>

VISITS: 1 visit every month

NCT ID: NCT05548127

ARV-471 Hormone Therapy with Abemaciclib for Advanced ER+, HER2- Breast Cancer

TACTIVE-U: AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL UMBRELLA STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF ARV-471 (PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH OTHER ANTICANCER TREATMENTS IN PARTICIPANTS AGED 18 YEARS AND OVER WITH ER+ ADVANCED OR METASTATIC BREAST CANCER, SUB-S... Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ARV-471, by mouth, daily</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ARV-471 is an experimental hormone therapy called a PROTAC protein degrader that breaks down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®) is a type of targeted therapy called a CDK 4/6 inhibitor. CDK4/6 inhibitors block two proteins, CDK4 and CDK6, that help cancer grow.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05548127' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://Tactivestudy.com' target='_blank'>Pfizer: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.pfizerclinicaltrials.com/nct05548127-or-nct05573555-advanced-and-metastatic-breast-cancer-trial' target='_blank'>Pfizer: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.arvinas.com/research-and-development/estrogen-receptor/' target='_blank'>Arvinas Estrogen Receptor: ARV-471 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/verzenio' target='_blank'>Breastcancer.org: Abemaciclib (Verzenio®)</a> </li></ul>

NCT ID: NCT05563220

Elacestrant Hormone Therapy with Anti-Cancer Therapies for Metastatic ER+, HER2- Breast Cancer

A Phase 1b/2, Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Patients With Metastatic Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 4 groups based on your situation: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Elacestrant (Orserdu®), daily</li> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®), daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Elacestrant (Orserdu®), daily</li> <li class="seamTextUnorderedListItem">Everolimus (Afinitor®), daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Elacestrant (Orserdu®), daily</li> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®), daily, 3 weeks on, 1 week off</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 4</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Elacestrant (Orserdu®), daily</li> <li class="seamTextUnorderedListItem">Physician's choice of palbociclib (Ibrance®), abemaciclib (Verzenio®), or ribociclib (Kisqali®), daily, 3 weeks on, 1 week off</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Elacestrant (Orserdu®) is a type of hormone therapy called a selective estrogen receptor degrader (SERD). SERDs work by binding to and breaking down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®) is a type of targeted therapy called a PI3K inhibitor. Blocking the PI3K pathway may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Everolimus (Afinitor®) is a type of targeted therapy called a mTOR inhibitor. mTOR inhibitors work by interfering with the ability of cancer cells to divide and grow.</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), abemaciclib (Verzenio®), ribociclib (Kisqali®) are a type of targeted therapy called CDK 4/6 inhibitors. CDK 4/6 inhibitors block two enzymes, CDK 4 and CDK 6, that help cancer grow.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05563220' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/orserdu' target='_blank'>Breastcancer.org: Elacestrant (Orserdu®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/piqray' target='_blank'>Breastcancer.org: Alpelisib (Piqray®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/afinitor' target='_blank'>Breastcancer.org: Everolimus (Afinitor®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/kisqali' target='_blank'>Breastcancer.org: Ribociclib (Kisqali®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/what-are-cdk46-inhibitors' target='_blank'>Breastcancer.org: CDK 4/6 Inhibitors</a> </li></ul>

NEAREST SITE: 3 miles UCSF Medical Center-Mission Bay San Francisco,CA

VISITS: Please contact research site

NCT ID: NCT05564377

ComboMATCH: Targeted Therapy Directed by Genetic Testing for Advanced Breast Cancer

Molecular Analysis for Combination Therapy Choice (ComboMATCH) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Targeted therapy based on genetic testing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Genetic tests look at the unique genetic material (genes) of tumor cells.</li> <li class="seamTextUnorderedListItem">People with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: AKT, ERK, MEK, NF1, RAF, RAS</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05564377' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/news-events/press-releases/2023/combomatch-precision-medicine-cancer-initiative' target='_blank'>National Cancer Institute: ComboMATCH</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy' target='_blank'>Breastcancer.org: Targeted Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mayoclinic.org/tests-procedures/precision-medicine-breast-cancer/about/pac-20385240' target='_blank'>Mayo Clinic: Precision Medicine for Breast Cancer</a> </li></ul>

NEAREST SITE: 3 miles Kaiser Permanente-San Francisco San Francisco,CA

VISITS: 1 visit every 3 months for 1.5 years

NCT ID: NCT05568472

Monitoring Symptoms to Help Women Continue Taking Hormone Therapy for Stage I-III Breast Cancer

A Randomized Phase III Trial Comparing Active Symptom Monitoring Plus Patient Education Versus Patient Education Alone to Improve Persistence With Endocrine Therapy in Young Women With Stage I-III Breast Cancer (ASPEN) Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Receive standard of care hormone therapy</li> <li class="seamTextUnorderedListItem">Receive health education materials</li> <li class="seamTextUnorderedListItem">Attend clinic visits, every 3 months for 1.5 years</li> <li class="seamTextUnorderedListItem">Report symptoms, by email, text, or phone, weekly for 6 months, then monthly for 1 year</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Receive standard of care hormone therapy</li> <li class="seamTextUnorderedListItem">Receive health education materials</li> <li class="seamTextUnorderedListItem">Attend clinic visits, every 3 months for 1.5 years</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Hormone therapy is a common treatment for hormone receptor positive (HR+) breast cancer.</li> <li class="seamTextUnorderedListItem">Hormone therapy can cause side effects which may cause some women to stop treatment early. Asking about symptoms may help women continue taking hormone therapy.</li> <li class="seamTextUnorderedListItem">Health education materials contain information about breast cancer, side effects of breast cancer medicines, and ways to help with heart health.</li> <li class="seamTextUnorderedListItem">Questionnaires can be completed in English or Spanish.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women will also be given a drug that will put women in temporary menopause.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05568472' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/research-news/20070906b' target='_blank'>Breastcancer.org: Side Effects of Hormone Therapy</a> </li></ul>

NCT ID: NCT05573555

ARV-471 Hormone Therapy with Ribociclib for Advanced ER+, HER2- Breast Cancer

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ARV-471, by mouth, daily</li> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®), by mouth, daily, 3 weeks on, 1 week off</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ARV-471 is an experimental hormone therapy called a PROTAC protein degrader that breaks down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®) is a type of targeted therapy called a CDK 4/6 inhibitor. CDK4/6 inhibitors block two proteins, CDK4 and CDK6, that help cancer grow.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05573555' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://Tactivestudy.com' target='_blank'>Pfizer: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.pfizerclinicaltrials.com/nct05548127-or-nct05573555-advanced-and-metastatic-breast-cancer-trial' target='_blank'>Pfizer: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.arvinas.com/research-and-development/estrogen-receptor/' target='_blank'>Arvinas Estrogen Receptor: ARV-471 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/kisqali' target='_blank'>Breastcancer.org: Ribociclib (Kisqali®)</a> </li></ul>

NCT ID: NCT05629585

Dato-DXd Antibody Drug Conjugate for Stage I-III Triple-Negative Breast Cancer

A Phase 3 Open-label, Randomised Study of Datopotamab Deruxtecan (DatoDXd) With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Who Have Residual Invasive Disease in the Breast and/or Axillary Lymph Nodes at Surgical Resection Following Neoadjuvant Systemic Therapy (TROPION... Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 3 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Datopotamab deruxtecan (abbreviated Dato-DXd), by IV, every 3 weeks for 6 months</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®), by IV, every 3 weeks for 7 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Datopotamab deruxtecan (abbreviated Dato-DXd), by IV, every 3 weeks for 6 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3 (Investigator's Choice)</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Capecitabine (Xeloda®), by mouth, daily (for 2 weeks in a 3-week cycle) for 6 months</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks for 7 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Datopotamab deruxtecan (abbreviated Dato-DXd) is an antibody-drug conjugate that kills cancer cells.</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®) is a type of immunotherapy called a PD-L1 inhibitor. It works by stimulating the body's immune system to go after cancer cells. It is approved to treat some cancers, but its use in breast cancer is considered experimental.</li> <li class="seamTextUnorderedListItem">Capecitabine (Xeloda®) is a chemotherapy commonly used to treat breast cancer.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05629585' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://ascopost.com/issues/october-10-2022-supplement-breast-cancer-almanac/datopotamab-deruxtecan-shows-activity-in-advanced-triple-negative-breast-cancer/' target='_blank'>ASCO: Dato-DXd</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancertherapyadvisor.com/home/news/conference-coverage/asco-2021/asco-2021-breast-cancer-in-depth/breast-cancer-durvalumab-neoadjuvant-chemo-treatment-risk/#:~:text=June%2024%2C%202021-,Durvalumab%20Improves%20Survival%20When%20Added%20to,in%2' target='_blank'>Cancer Therapy Advisor: Durvalumab</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/xeloda' target='_blank'>Breastcancer.org: Capecitabine</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab</a> </li></ul>

NEAREST SITE: 3 miles UCSF Medical Center San Francisco,CA

VISITS: 1-2 visits every 3 weeks for 6 months

NCT ID: NCT05633654

Sacituzumab Govitecan with Pembrolizumab for Stage I-III Triple Negative Breast Cancer with Residual Disease

A Randomized, Open-label, Phase 3 Study of Adjuvant Sacituzumab Govitecan and Pembrolizumab Versus Treatment of Physician's Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Sacituzumab govitecan (Trodelvy®), by IV, weekly, 2 weeks on, 1 week off, 6 months</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks, 6 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Capecitabine (Xeloda®), by mouth, daily, 2 weeks on, 1 week off, 6 months (optional)</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks, 6 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Sacituzumab govitecan(Trodelvy®) is a type of targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">The antibody in sacituzumab govitecan (Trodelvy®) targets TROP2 proteins. It delivers the chemotherapy irinotecan.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">Capecitabine (Xeloda®) is a chemotherapy drug commonly used to treat breast cancer.</li> <li class="seamTextUnorderedListItem">Residual disease refers to cancer cells that are present after treatment.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05633654' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/trodelvy' target='_blank'>Breastcancer.org: Sacituzumab Govitecan (Trodelvy®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/xeloda' target='_blank'>Breastcancer.org: Capecitabine (Xeloda®)</a> </li></ul>

NCT ID: NCT05694715

Niraparib Targeted Therapy and Irinotecan Chemotherapy for Advanced Breast Cancer with BRCA1, BRCA2, ATM, and PALB2 Mutations

Combination Therapy of Niraparib and Irinotecan in Cancers With Mutations in DNA Repair Genes Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Niraparib (Zejula®), by mouth, 1 week on, 2 weeks off</li> <li class="seamTextUnorderedListItem">Irinotecan (Camptosar®), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Niraparib (Zejula®) is a type of targeted therapy called a PARP inhibitor. It works by blocking poly (ADP-ribose) polymerase, an enzyme that helps cancer cells grow by repairing their DNA.</li> <li class="seamTextUnorderedListItem">Irinotecan (Camptosar®) is a type of chemotherapy drug.</li> <li class="seamTextUnorderedListItem">Niraparib (Zejula®) and irinotecan (Camptosar®) are approved to treat certain types of cancer. Their use in breast cancer is considered experimental.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: BRCA1, BRCA2, ATM, PALB2</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05694715' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a617007.html' target='_blank'>Medline Plus: Niraparib (Zejula®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a608043.html' target='_blank'>Medline Plus: Irinotecan (Camptosar®)</a> </li></ul>

NCT ID: NCT05705401

Anti-HER2 Targeted Therapy With or Without Radiation for Women with DCIS and Stage I-III HER2 Positive Breast Cancer

A Phase III Randomized Trial of Radiotherapy Optimization for Low-Risk HER2-Positive Breast Cancer (HERO) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Standard of Care With Radiation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Continue standard of care anti-HER2 targeted therapy</li> <li class="seamTextUnorderedListItem">Radiation</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care Without Radiation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Continue standard of care anti-HER2 targeted therapy</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Due to the low risk of recurrence (cancer coming back) of people in this trial, researchers think there may be a low benefit of radiation in addition to anti-HER2 targeted therapy after surgery.</li> <li class="seamTextUnorderedListItem">Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors.</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®), trastuzumab (Herceptin®), and pertuzumab (Perjeta®) are examples of anti-HER2 targeted therapies used to treat HER2 positive (HER2+) breast cancer.</li> <li class="seamTextUnorderedListItem">A lumpectomy is sometimes called a partial mastectomy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05705401' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/radiation-therapy' target='_blank'>Breastcancer.org: Radiation</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/what-are-anti-her2-therapies' target='_blank'>Breastcancer.org: Anti-HER2 Targeted Therapy</a> </li></ul>

NCT ID: NCT05768139

STX-478 Targeted Therapy for Advanced HR+, HER2- Breast Cancer with a PI3K Mutation

First-in-Human Study of STX-478, a Mutant-Selective PI3Kα Inhibitor as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumor Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">STX-478</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">STX-478</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">STX-478 is an experimental targeted therapy called a PI3K inhibitor. Blocking the PI3K pathway may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor degrader (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Targets or mutations: PI3K</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05768139' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.scorpiontx.com/pipeline/' target='_blank'>Scorpion Therapeutics: STX-478 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li></ul>

NEAREST SITE: 3 miles California Pacific Medical Center San Francisco,CA

NCT ID: NCT05787587

IDE161 for Advanced Breast Cancer with a BRCA Mutation

A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">IDE-161, by mouth</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">IDE161 targets poly(ADP-ribose) glycohydrolase (PARG) and may block cancer cell growth in people with a BRCA1 mutation.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05787587' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.targetedonc.com/view/phase-1-trial-of-ide161-doses-first-patient-with-advanced-solid-tumors' target='_blank'>Targeted Oncology: Trial for IDE161</a> </li><li class='seamTextUnorderedListItem'><a href='https://filecache.investorroom.com/mr5ir_ideayabio/277/AACR%20Annual%20Meeting%202023%20Poster%206093_PARG_Final.pdf' target='_blank'>Ideayabio Research Poster: IDE161</a> </li></ul>

PHASE: III-IV

NCT ID: NCT05807074

Tranexamic Acid During Bilateral Mastectomy with Reconstruction for Prevention, DCIS, or Stage I-III Breast Cancer

The Impact of Tranexamic Acid in Reducing Hematoma and Seroma Formation in Reconstructive Post-oncologic Breast Surgery Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Bilateral mastectomy with immediate reconstruction</li> <li class="seamTextUnorderedListItem">Tranexamic acid (TXA) to one breast during surgery (experimental)</li> <li class="seamTextUnorderedListItem">Saline applied to one breast during surgery (control)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Bleeding and fluid build-up are common complications after mastectomies which can interfere with breast reconstruction, increase the risk of infection, slow wound healing, and potentially delay cancer treatments.</li> <li class="seamTextUnorderedListItem">Tranexamic acid (TXA) is a drug that improves blood clotting. Applying it to the surgical site before closing the incision may prevent bleeding and fluid build-up.</li> <li class="seamTextUnorderedListItem">A bilateral mastectomy is a surgical procedure involving removing both breasts to prevent or remove breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05807074' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/surgery/mastectomy' target='_blank'>Breastcancer.org: Mastectomy</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a612021.html' target='_blank'>Medline Plus: Tranexamic Acid</a> </li></ul>

NCT ID: NCT05831995

ABM-168 Targeted Therapy for Advanced Breast Cancer with RAS, RAF, or NF-1 Mutations

A Phase I, First-In-Human, Multicenter, Open Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety and Efficacy of ABM-168 Administered Orally in Adult Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ABM-168, by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ABM-168 is an experimental targeted therapy called a MEK inhibitor that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05831995' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.clinicaltrialsarena.com/news/abm-first-patient-solid-tumours/' target='_blank'>ABM Therapeutics Corporation: ABM-168 Press Release</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-terms/def/mek-inhibitor' target='_blank'>National Cancer Institute: MEK Inhibitor</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2022-0763.html' target='_blank'>MD Anderson Cancer Center: Trial Information Page</a> </li></ul>

NEAREST SITE: 3 miles UCSF Comprehensive Cancer Ctr San Francisco,CA

VISITS: 1 visit every 1-2 weeks

NCT ID: NCT05852691

RO7247669 Bispecific Antibody with Chemotherapy for Advanced Triple Negative or HER2 Low, PD-L1 Positive Breast Cancer

A Phase II, Multicenter, Randomized, Double-Blind Study of RO7247669 Combined With Nab-Paclitaxel Compared With Pembrolizumab Combined With Nab-Paclitaxel in Participants With Previously Untreated, PD-L1-Positive, Locally-Advanced Unresectable or Metastatic Triple-Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">RO7247669, by IV, every 3 weeks</li> <li class="seamTextUnorderedListItem">Nab-paclitaxel (Abraxane®), by IV, weekly, 3 weeks on, 1 week off</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks</li> <li class="seamTextUnorderedListItem">Nab-paclitaxel (Abraxane®), by IV, weekly, 3 weeks on, 1 week off</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">RO7247669 is an experimental targeted therapy called a bispecific antibody.</li> <li class="seamTextUnorderedListItem">A bispecific antibody binds to two distinct targets and may work better than traditional antibody drugs.</li> <li class="seamTextUnorderedListItem">RO7247669 is a bispecific antibody that targets PD-1 (programmed death-1) and LAG-3 (lymphocyte-activation gene 3).</li> <li class="seamTextUnorderedListItem">Nab-paclitaxel (Abraxane®) is a chemotherapy drug.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05852691' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/tobemstomig' target='_blank'>National Cancer Institute: Tobemstomig (RO7247669)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/abraxane' target='_blank'>Breastcancer.org: Nab-Paclitaxel (Abraxane®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li></ul>

NCT ID: NCT05879926

Hormone Therapy and Ovarian Suppression With or Without Chemotherapy for Premenopausal Women with Stage I-III HR+, HER2- Breast Cancer

A Phase III Adjuvant Trial Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients With pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score Less Than or Equal to 25 (OFSET) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Aromatase inhibitor, 5 years</li> <li class="seamTextUnorderedListItem">Ovarian function suppression, every 1-3 months, 5 years</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Chemotherapy</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Aromatase inhibitor, 5 years</li> <li class="seamTextUnorderedListItem">Ovarian function suppression, every 1-3 months, 5 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Aromatase inhibitors are a type of hormone therapy that block some production of estrogen that helps cancer grow. The approved aromatase inhibitors are anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®).</li> <li class="seamTextUnorderedListItem">Ovarian suppression can stop the ovaries from making estrogen, putting you into temporary menopause. This prevents the tumor from receiving estrogen it needs to grow.</li> <li class="seamTextUnorderedListItem">The Oncotype DX test can help determine the chance of the cancer coming back and whether a person will benefit from chemotherapy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05879926' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/aromatase-inhibitors' target='_blank'>Breastcancer.org: Aromatase Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.komen.org/breast-cancer/treatment/type/hormone-therapy/ovarian-suppression/' target='_blank'>Susan G. Komen: Ovarian Suppression</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/screening-testing/oncotype-dx' target='_blank'>Breastcancer.org: Oncotype DX</a> </li></ul>

NCT ID: NCT05929768

Shorter Chemotherapy and Immunotherapy Treatment Before Surgery for Stage I-III Triple Negative Breast Cancer

Shorter Anthracycline-Free Chemo Immunotherapy Adapted to Pathological Response in Early Triple Negative Breast Cancer (SCARLET), A Randomized Phase III Study Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Usual Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV</li> <li class="seamTextUnorderedListItem">Carboplatin (Carboplatin®), by IV</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Doxorubicin (Adriamycin®), by IV</li> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®), by IV</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, before and/or after surgery</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Docetaxel (Taxotere®), by IV</li> <li class="seamTextUnorderedListItem">Carboplatin (Paraplatin®), by IV</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, before and/or after surgery</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Docetaxel (Taxotere®), carboplatin (Paraplatin®), paclitaxel (Taxol®), doxorubicin (Adriamycin®), and cyclophosphamide (Cytoxan®) are chemotherapy drugs commonly used to treat breast cancer.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">Shorter chemotherapy treatment without doxorubicin (Adriamycin®) chemotherapy may work the same as usual chemotherapy treatment for stage I-III triple negative breast cancer.</li> <li class="seamTextUnorderedListItem">Neoadjuvant therapy is when you receive treatment, like chemotherapy, before surgery. Doctors use it to shrink tumors and to see how your cancer responds to the given therapies.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05929768' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/chemotherapy' target='_blank'>Breastcancer.org: Chemotherapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li></ul>

NEAREST SITE: 3 miles Zuckerberg San Francisco General San Francisco,CA

VISITS: 8 visits within 3 months

NCT ID: NCT06055803

HEART-ACT Program to Improve Heart Health After Breast Cancer Treatment

The Heart Health After Cancer Treatment (HEART-ACT): A Pilot Study of a Multi-disciplinary Health Behavior Intervention in People With a History of Breast Cancer to Reduce Heart Disease Risk After Cancer Treatment. Scientific Title

• <p class="seamTextPara"> You will receive the following as part of the HEART-ACT program: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Visit to create individualized plan and goals</li> <li class="seamTextUnorderedListItem">Health behavior sessions, 3 months</li> <li class="seamTextUnorderedListItem">Exercise program, 3 months</li> <li class="seamTextUnorderedListItem">Fitness tests</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Some breast cancer treatments can cause or increase the risk of heart problems, which is called cardiotoxicity.</li> <li class="seamTextUnorderedListItem">The HEART-ACT program covers physical activity, nutrition, emotional well-being, cardiovascular risk, survivorship, and personalized topics such as stopping smoking.</li> <li class="seamTextUnorderedListItem">The program will alternate each week between group and individual sessions and in-person and virtual sessions.</li> <li class="seamTextUnorderedListItem">Individual sessions will be led by a health promotion specialist (nurse or exercise physiologist). These sessions include reviewing goals and making a plan for the next 2 weeks.</li> <li class="seamTextUnorderedListItem">Participants will exercise as part of individual and group sessions. Participants will also be asked to exercise on their own, with a goal of working up to 2.5 hours each week of exercise and 2 strength training sessions.</li> <li class="seamTextUnorderedListItem">At the end of the program, there will be a graduation session to honor the participant's achievement and establish a plan for maintenance after the program.</li> <li class="seamTextUnorderedListItem">This trial is also available in Spanish and Cantonese.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06055803' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://heartact.ucsf.edu/' target='_blank'>University of California San Francisco: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.webmd.com/breast-cancer/heart-health-breast-cancer-treatment' target='_blank'>WebMD: Heart Health After Breast Cancer Treatment</a> </li></ul>

VISITS: 1 visit every 6 months for 5 years

NCT ID: NCT06075953

Hormone Therapy and Active Surveillance for Women with HR+ DCIS

DCIS: RECAST Trial -Ductal Carcinoma In Situ: Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: a Breast Cancer Prevention Pilot Study Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Hormone therapy (standard of care or experimental) for 6 months</li> <li class="seamTextUnorderedListItem">MRI scans, 2 times within 6 months</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Surgery (if needed)</li> </ul> <p class="seamTextPara"> or: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Continue on hormone therapy for 2-5 years</li> <li class="seamTextUnorderedListItem">Alternating MRI scan or mammogram every 6 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">After evaluation at 6 months, participants will either have surgery (if recommended) or continue on the treatment for 2-5 years.</li> <li class="seamTextUnorderedListItem">Tamoxifen (Nolvadex®) is a type of hormone therapy called a selective estrogen receptor modulator (SERM). SERMs work by blocking the activity of estrogen.</li> <li class="seamTextUnorderedListItem">(Z)-endoxifen is similar to tamoxifen.</li> <li class="seamTextUnorderedListItem">Aromatase inhibitors are a type of hormone therapy commonly used to treat hormone receptor positive breast cancer. The approved aromatase inhibitors are anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®).</li> <li class="seamTextUnorderedListItem">Elacestrant (Orserdu®) is a type of hormone therapy called a selective estrogen receptor downregulator (SERD). SERDs work by blocking the activity of estrogen in people with mutations in the ESR1 gene.</li> <li class="seamTextUnorderedListItem">Testosterone is a hormone that may reduce the risk of breast cancer.</li> <li class="seamTextUnorderedListItem">A magnetic resonance imaging (MRI) scan produces body pictures created by using magnetic energy rather than x-ray energy.</li> <li class="seamTextUnorderedListItem">A mammogram is a breast cancer screening procedure involving taking an x-ray picture of the breast.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06075953' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.quantumleaphealth.org/portfolio/dcis' target='_blank'>Quantum Leap Healthcare Collaborative: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/types/ductal-carcinoma-in-situ' target='_blank'>Breastcancer.org: DCIS</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy' target='_blank'>Breastcancer.org: Hormone Therapy</a> </li></ul>

NCT ID: NCT06177171

ASTX727 Targeted Therapy with Olaparib for Advanced Breast Cancer with Certain Mutations

A Phase I/Ib Study of Olaparib and ASTX727 in BRCA1/2- and HRD-mutated Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ASTX727, by mouth</li> <li class="seamTextUnorderedListItem">Olaparib (Lynparza®), by mouth, every 2 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ASTX727 is an experimental targeted therapy called a DNMT inhibitor. Blocking DNMT may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">ASTX727 is a combination of decitabine with cedazuridine.</li> <li class="seamTextUnorderedListItem">Olaparib (Lynparza®) is a type of targeted therapy called a PARP inhibitor. PARP inhibitors work by blocking the action of poly (ADP-ribose) polymerase, an enzyme that helps repair DNA.</li> <li class="seamTextUnorderedListItem">BRCA1, BRCA2, PALB2, ATM, and CHEK2 gene mutations are homologous recombination repair (HRR) or homologous recombination deficient (HRD) mutations.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06177171' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://astx.com/research-development/clinical-pipeline/oral-decitabine-and-cedazuridine-astx727-hematological-malignancies/' target='_blank'>Astex Pharmaceuticals: ASTX727 Drug Information Page</a> </li></ul>

NCT ID: NCT06188559

BB-1701 Antibody Drug Conjugate for Advanced HER2+ or HER2 Low Breast Cancer

An Open-label, Multicenter, Phase 2 Dose Optimization and Expansion Study to Evaluate the Safety and Efficacy of BB-1701, an Anti-human Epidermal Growth Factor Receptor 2 (Anti-HER2) Antibody-drug Conjugate (ADC), in Previously Treated Subjects With HER2-positive or HER2-low Unresectable or Metastatic Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BB-1701, by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BB-1701 is an experimental targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">BB-1701's antibody targets HER2, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called eribulin.</li> <li class="seamTextUnorderedListItem">In this trial, HER2+ is defined as IHC 3+ or IHC 2+/ISH+.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+ or 2+/ISH -.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06188559' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.blissbiopharma.com/Innovation?_l=en#Pipeline' target='_blank'>Eisai/Bliss Biopharmaceutical: BB-1701 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li></ul>

VISITS: Coincides with routine care

NCT ID: NCT06215469

Portable Scalp Cooling System to Reduce Hair Loss During Chemotherapy for Stage I-III Breast Cancer

Amma™ Portable Scalp Cooling System (PSCS) Study: A Post-market Study to Assess the Ability of the Portable Scalp Cooling System (PSCS) to Prevent Hair Loss in Women Receiving Specific Chemotherapy Regimens for Early-stage Breast Cancer (Cooler Heads) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Photographs of your hair</li> <li class="seamTextUnorderedListItem">Wear the AMMA Portable Scalp Cooling System 30 minutes before, during, and 2.5 hours after every chemotherapy visit</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Questionnaires</li> <li class="seamTextUnorderedListItem">Photographs of your hair</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Many chemotherapy medications cause hair loss.</li> <li class="seamTextUnorderedListItem">The AMMA Portable Scalp Cooling System is a small refrigeration device that is designed to reduce hair loss. It circulates liquid coolant at low pressure through a cooling cap on your head.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06215469' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://coolerheads.com/#how-amma-works' target='_blank'>Amma Portable Scalp Cooling System</a> </li></ul>

NEAREST SITE: 3 miles University of California San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center San Francisco,CA

NCT ID: NCT06264921

NKT3447 CDK2 Inhibitor for Advanced Triple Negative or HR+, HER2- Breast Cancer

A Phase 1, First-in-Human, Open-Label Study to Evaluate the Safety, Tolerability, PK, and Preliminary Anti-tumor Activity of the Novel Orally Available CDK2 Inhibitor NKT3447 in Adults With Advanced/Metastatic Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NKT3447, by mouth</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NKT3447 is an experimental targeted therapy called a CDK2 inhibitor. CDK2 inhibitors block the enzyme/protein CDK2 that helps cancer grow.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06264921' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.nikangtx.com/science-and-pipeline/' target='_blank'>NiKang Therapeutics: NKT3447 Drug Information Page</a> </li></ul>

NEAREST SITE: 5 miles University of California, San Francisco San Francisco,CA

NCT ID: NCT05315700

ORIC-114 Targeted Therapy for Advanced HER2+ Breast Cancer

An Open-Label, Phase 1/2 Study of ORIC-114 as a Single Agent or in Combination With Chemotherapy, in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ORIC-114, by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ORIC-114, by mouth, daily</li> <li class="seamTextUnorderedListItem">Carboplatin (Paraplatin®) and/or pemetrexed (Alimta®)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ORIC-114 is an experimental anti-HER2 targeted therapy and blocks EGFR and HER2. Blocking EGFR and HER2 may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Carboplatin (Paraplatin®) and pemetrexed (Alimta®) are chemotherapy drugs.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05315700' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://oricpharma.com/pipeline/#oric114' target='_blank'>ORIC Pharmaceuticals: ORIC-114 Drug Information Page</a> </li></ul>

NCT ID: NCT05964504

PLUMB Registry for Metastatic Lobular Breast Cancer

Improving Survival for Those With Metastatic Lobular Breast Cancer Through Development of the Multi-center PLUMB Registry-a Prospective Study of LobUlar Metastatic Breast Cancer Scientific Title

• <p class="seamTextPara"> You will provide the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Blood samples</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Blood samples will be used to study the relationship between ctDNA and disease progression.</li> <li class="seamTextUnorderedListItem">Circulating tumor DNA (ctDNA) are small pieces of cancer cell DNA in the bloodstream.</li> <li class="seamTextUnorderedListItem">This trial will also develop an ongoing platform for evaluating new imaging tools, tumor markers, and participant recruitment for clinical trials.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05964504' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://clinicaltrials.ucsf.edu/trial/NCT05964504' target='_blank'>University of California, San Francisco: Trial Information Page</a> </li></ul>

NEAREST SITE: 6 miles Cedars-Sinai Los Angeles,CA

NCT ID: NCT05720039

Nipple Sparing Mastectomy with da Vinci SP Surgical System for Women with Stage I-III Breast Cancer

A Prospective, Multicenter Randomized Controlled Trial(RCT) of the da Vinci® SPâ„¢ Surgical System vs Open Surgery in Nipple Sparing Mastectomy (NSM) Procedures Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Robotic-assisted nipple sparing mastectomy with da Vinci single port (SP) Surgical System</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Open nipple sparing mastectomy</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">A mastectomy is surgery to remove a breast.</li> <li class="seamTextUnorderedListItem">A nipple sparing mastectomy (NSM) leaves most of the healthy breast skin, including the nipple.</li> <li class="seamTextUnorderedListItem">The da Vinci single port (SP) Surgical System is an experimental surgery system designed for surgeons to perform minimally invasive surgery, such as nipple sparing mastectomy.</li> <li class="seamTextUnorderedListItem"> Your surgeon performs the surgery using the da Vinci SP Surgical System.</li> <li class="seamTextUnorderedListItem">The da Vinci SP Surgical System is approved for use during other surgeries.</li> <li class="seamTextUnorderedListItem">Robotic-assisted NSM with da Vinci SP Surgical System may be less invasive than standard of care open NSM.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05720039' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.intuitive.com/en-us/patients/da-vinci-robotic-surgery/about-the-systems' target='_blank'>Intuitive Surgical Device Information Page: About the Da Vinci Surgical System</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cedars-sinai.org/health-library/diseases-and-conditions/n/nipple-sparing-mastectomy.html' target='_blank'>Cedars-Sinai: Nipple Sparing Mastectomy</a> </li></ul>

NEAREST SITE: 7 miles xCures Oakland,CA

NCT ID: NCT05461430

Malignant Fluid Test to Predict Response to Treatment for Breast Cancer

Mass Response of Malignant Fluid Cells as a Biomarker for Rapid Therapy Guidance Scientific Title

• <p class="seamTextPara"> Additional malignant fluid will be collected as part of a standard of care procedure.</p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Malignant fluid is the build up of fluid and cancer cells in your body.</li> <li class="seamTextUnorderedListItem">A cancer cell's mass response (weight change) indicates when a cancer cell begins responding to a drug before it dies.</li> <li class="seamTextUnorderedListItem">The results from the mass response test may be used by your doctor to choose your next treatment(s).</li> <li class="seamTextUnorderedListItem">Additional malignant fluid will be collected as part of a standard of care procedure.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05461430' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.travera.com/clinical-study-summary' target='_blank'>Travera Trial Information Page: TRV-003</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.travera.com/technology' target='_blank'>Travera: Mass Response Test</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.thoracic.org/patients/patient-resources/resources/malignant-pleural-effusions.pdf' target='_blank'>American Thoracic Society: Malignant Fluid</a> </li></ul>

NEAREST SITE: 8 miles Kaiser Permanente Cancer Treatment Center South San Francisco,CA

NCT ID: NCT03488693

Radiation or No Radiation to Treat Low Risk Node Positive Breast Cancer

TAILOR RT: A Randomized Trial of Regional Radiotherapy in Biomarker Low Risk Node Positive Breast Cancer (TAILOR RT) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Radiation (following breast surgery)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">No radiation (following breast surgery)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Radiation is given to reduce the risk of the cancer coming back in the breast. </li> <li class="seamTextUnorderedListItem">It is not known if radiation therapy after surgery improves outcomes in women with low-risk breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03488693' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://ww5.komen.org/BreastCancer/SideEffectsofRadiationTherapy.html' target='_blank'>Susan G. Komen: Side Effects of Radiation Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.eortc.org/blog/2018/03/23/many-women-with-early-breast-cancer-have-a-very-low-risk-of-a-locoregional-recurrence-five-years-after-surgery/' target='_blank'>European Organisation for Research and Treatment of Cancer: Many women with early breast cancer have a very low risk of a locoregional recurrence 5 years after surgery</a> </li></ul>

NEAREST SITE: 8 miles Bay Area Breast Surgeons Inc Emeryville,CA

NCT ID: NCT03723928

Imaging and Tumor Mark Tests to Monitor Metastatic HR Positive, HER2 Negative Breast Cancer

Randomized Non-Inferiority Trial Comparing Overall Survival of Patients Monitored With Serum Tumor Marker Directed Disease Monitoring (STMDDM) Versus Usual Care in Patients With Metastatic Hormone Receptor Positive Breast Cancer (SWOG-S1703) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Standard of care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Imaging (CT and/or PET scans), at least every 3 months, ongoing</li> <li class="seamTextUnorderedListItem">Tumor Marker Test, if ordered by your doctor</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Tumor Marker Tests, every 1 to 2 months, ongoing</li> <li class="seamTextUnorderedListItem">Imaging (CT and/or PET scans), only if need is shown by a Tumor Marker Test</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Blood draws</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">This imaging trial will compare using blood tests to PET/CT scans for monitoring tumor growth. </li> <li class="seamTextUnorderedListItem">The tumor markers that will be tested for in this study are CA 15-3, CA27.29, and CEA.</li> <li class="seamTextUnorderedListItem">The imaging tests will be those ordered by your doctor.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03723928' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/symptoms/testing/types/blood_marker' target='_blank'>Breastcancer.org: Blood Marker Tests</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.net/about-us/collaborations/top-five-list-oncology/choosing-wisely®-top-five-cancer-related-tests-procedures-and-treatments-many-patients-do-not-need/topic-4-follow-tumor-marker-tests-and-imaging-tests-people-treated-breast-cancer' target='_blank'>ASCO Cancer.net: Follow-up Tumor Marker Tests and Imaging Tests for People Treated for Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet' target='_blank'>NCI: Tumor Markers</a> </li><li class='seamTextUnorderedListItem'><a href='https://ozarkscancerresearch.org/wp-content/uploads/2019/04/SWOG-S1703.pdf' target='_blank'>Cancer Research for the Ozarks: Trial Information Page</a> </li></ul>

VISITS: 1 visit every week (2 weeks on, 1 week off), ongoing

NCT ID: NCT04647916

Sacituzumab Govitecan for HER2 Negative Breast Cancer Brain Metastases

A Phase II Trial of Sacituzumab Govitecan (IMMU-132) (NSC #820016) for Patients With HER2-Negative Breast Cancer and Brain Metastases Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Sacituzumab govitecan (Trodelvy®), by IV, every week (2 weeks on, 1 week off), ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Sacituzumab govitecan (Trodelvy®) is an antibody-drug conjugate (ADC). This means it uses an antibody that targets cancer cells to deliver a chemotherapy directly to these cells.</li> <li class="seamTextUnorderedListItem">The antibody in this drug targets TROP2 proteins. It delivers the chemotherapy irinotecan. Irinotecan is approved for use in many other types of cancer.</li> <li class="seamTextUnorderedListItem">Sacituzumab govitecan is approved for use in people with metastatic triple negative breast cancer who have already received at least two other therapies for metastatic disease, but its use in this trial is considered experimental.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04647916' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/news-events/cancer-currents-blog/2020/fda-sacituzumab-govitecan-triple-negative-breast-cancer' target='_blank'>NCI Cancer Currents Blog: Sacituzumab Govitecan Approved for Metastatic Triple-Negative Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.targetedonc.com/view/sacituzumab-govitecan-shows-pfs-benefit-for-patients-with-mtnbc-and-brain-metastases' target='_blank'>Targeted Oncology: Sacituzumab Govitecan Shows PFS Benefit for Patients With mTNBC and Brain Metastases</a> </li></ul>

VISITS: 2 visits in 1 year

NCT ID: NCT05334069

Collecting Blood Samples From People With and Without Breast Cancer to Evaluate Tests for Early Cancer Detection

Blinded Reference Set for Multicancer Early Detection Blood Tests Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Provide blood samples, 2 times</li> <li class="seamTextUnorderedListItem">Provide tissue samples (for people with cancer), 2 times</li> <li class="seamTextUnorderedListItem">Complete questionnaires, 2 times</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Collecting and storing samples of blood and tissue from patients with and without breast cancer to study in the laboratory may help researchers develop tests for the early detection of cancers.</li> <li class="seamTextUnorderedListItem">This trial is also available in Spanish.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05334069' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis' target='_blank'>National Cancer Institute: How Cancer Is Diagnosed</a> </li></ul>

NEAREST SITE: 10 miles Alta Bates Summit Medical Center; Comprehensive Cancer Center Berkeley,CA

NCT ID: NCT05306340

Hormone Therapy and Targeted Therapy for ER+, HER2- Advanced Breast Cancer

A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With Exemestane Plus Everolimus in Patients With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Giredestrant, by mouth, daily</li> <li class="seamTextUnorderedListItem">Everolimus (Afinitor®), by mouth, daily</li> <li class="seamTextUnorderedListItem">Dexamethasone mouthwash, 4 times daily for at least 8 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Control</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Exemestane (Aromasin®), by mouth, daily</li> <li class="seamTextUnorderedListItem">Everolimus (Afinitor®), by mouth, daily</li> <li class="seamTextUnorderedListItem">Dexamethasone mouthwash, 4 times daily for at least 8 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Giredestrant is an experimental hormone therapy called a SERD (selective estrogen receptor degrader). SERDs work by binding to and breaking down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Exemestane (Aromasin®) is a type of hormone therapy called an aromatase inhibitor. Aromatase inhibitors block some production of estrogen that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Everolimus (Afinitor®) is a type of targeted therapy called a mTOR inhibitor. mTOR inhibitors work by interfering with the ability of cancer cells to divide and grow.</li> <li class="seamTextUnorderedListItem">Dexamethasone mouthwash is an anti-inflammatory medication used to prevent and treat side effects of some cancer drugs.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women and men will also be given a drug that will put women in temporary menopause.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05306340' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.genentechoncology.com/pipeline-molecules/serd-3.html' target='_blank'>Genentech Drug Information Page: Giredestrant</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/oral-serds/' target='_blank'>Metastatic Trial Talk: Update on Oral SERDs for Estrogen Receptor-Positive MBC</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/aromasin' target='_blank'>Breastcancer.org: Exemestane (Aromasin®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/afinitor' target='_blank'>Breastcancer.org: Everolimus (Afinitor®)</a> </li></ul>

NEAREST SITE: 15 miles Marin Cancer Care, Inc Greenbrae,CA

VISITS: 1 visit every 3 months, for 13 months

NCT ID: NCT04906395

Experimental Ovarian Suppression Therapy Every 3 Months for Premenopausal Women and Men with Stage I-III Hormone-Positive Breast Cancer

Phase 3,Single Arm,Open-Label Study Evaluating Ovarian Suppression Following 3 Month Leuprolide Acetate For Injectable Suspension (TOL2506) in Combination With Endocrine Therapy in Premenopausal Subjects With Hormone-Receptor-Positive (HR+),Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Leuprolide acetate, by injection, every 3 months, for 1 year</li> <li class="seamTextUnorderedListItem">Your doctor's choice of tamoxifen or an aromatase inhibitor, by mouth, daily, for 1 year</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Leuprolide acetate is a type of hormone therapy called a <q>luteinizing hormone-releasing hormone</q> (LHRH) agonist. It is approved for use in people with prostate cancer, but its use in breast cancer is considered experimental.</li> <li class="seamTextUnorderedListItem">Leuprolide acetate is being used in this trial to suppress ovarian function (induce menopause) in women who are premenopausal.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04906395' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/research-news/guidelines-on-ovary-suppression-for-early-HR-pos' target='_blank'>Breastcancer.org: ASCO Updates Guidelines on Ovarian Suppression</a> </li><li class='seamTextUnorderedListItem'><a href='https://ascopubs.org/doi/10.1200/JCO.2006.07.2397' target='_blank'>Journal Article: Leuprolide Acetate Plus Aromatase Inhibition for Male Breast Cancer</a> </li></ul>

NEAREST SITE: 15 miles Marin Cancer Care Inc Greenbrae,CA

VISITS: 2 visits for 1 month, then 1 visit every month

NCT ID: NCT05646862

Targeted Therapy with Fulvestrant for HR+, HER2- Advanced Breast Cancer with a PIK3CA Mutation

A Phase III, Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Versus Alpelisib Plus Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Who Progressed During or After CDK4/6 Inhibitor and Endocrine Combinatio... Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Inavolisib, by mouth, daily</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), every 2 weeks for 1 month, then monthly</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard Treatment</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®), by mouth, daily</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), every 2 weeks for 1 month, then monthly</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Inavolisib is an experimental targeted therapy called a PI3K inhibitor.</li> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®) is a type of targeted therapy called a PI3K inhibitor.</li> <li class="seamTextUnorderedListItem">Blocking the PI3K pathway may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor degrader (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women and men will also be given a drug that will put women in temporary menopause.</li> <li class="seamTextUnorderedListItem">Targets or mutations: PIK3CA</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05646862' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.genentechoncology.com/pipeline-molecules/inavolisib.html' target='_blank'>Genentech Drug Information Page: Inavolisib</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/piqray' target='_blank'>Breastcancer.org: Alpelisib (Piqray®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex#:~:text=Faslodex%20(chemical%20name%3A%20fulvestrant),%2C%20HER2%2Dnegative%20breast%20cancer.' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li></ul>

NEAREST SITE: 15 miles Research Site Greenbrae,CA

NCT ID: NCT05774951

CAMBRIA-1: Camizestrant After At Least 2 Years of Hormone Therapy for Stage I-III ER+, HER2- Breast Cancer

A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety of Extended Therapy With Camizestrant Versus Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) in Patients With ER+/HER2- Early Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Camizestrant, by mouth, for 5 years</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Exemestane (Aromasin®), letrozole (Femara®), anastrozole (Arimidex®), or tamoxifen (Nolvadex®), by mouth, for 5 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Camizestrant is an experimental hormone therapy called a selective estrogen receptor degrader (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Exemestane (Aromasin®), letrozole (Femara®), and anastrozole (Arimidex®) are types of hormone therapy called aromatase inhibitors. Aromatase inhibitors block production of estrogen that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Tamoxifen (Nolvadex®) is a type of hormone therapy called a selective estrogen receptor modulator (SERM). SERMs work by blocking the activity of estrogen.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05774951' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.aacr.org/about-the-aacr/newsroom/news-releases/camizestrant-may-be-superior-to-fulvestrant-in-patients-with-hormone-receptor-positive-her2-negative-breast-cancer/' target='_blank'>American Association for Cancer Research: Camizestrant</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/aromatase-inhibitors' target='_blank'>Breastcancer.org: Aromatase Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/tamoxifen' target='_blank'>Breastcancer.org: Tamoxifen (Nolvadex®)</a> </li></ul>

NCT ID: NCT06065748

Giredestrant Hormone Therapy with a CDK Inhibitor for Advanced ER+, HER2- Breast Cancer

A Phase III Randomized, Open-Label Study Evaluating Efficacy and Safety of Giredestrant Compared With Fulvestrant, Both Combined With a CDK4/6 Inhibitor, in Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer With Resistance to Prior Adjuvant Endocrine Therapy Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Giredestrant, by mouth, daily</li> <li class="seamTextUnorderedListItem">CDK inhibitor, by mouth, daily</li> <li class="seamTextUnorderedListItem">FoundationOne Liquid CDx Assay blood test</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Control</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, 2 times in 1 month, then monthly</li> <li class="seamTextUnorderedListItem">CDK inhibitor, by mouth, daily</li> <li class="seamTextUnorderedListItem">FoundationOne Liquid CDx Assay blood test</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) and giredestrant are a type of hormone therapy called selective estrogen receptor degraders (SERDs). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Giredestrant is an experimental SERD.</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), abemaciclib (Verzenio®), ribociclib (Kisqali®) are a type of targeted therapy called CDK 4/6 inhibitors. CDK 4/6 inhibitors block two enzymes, CDK 4 and CDK 6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">The FoundationOne Liquid CDx Assay blood test will identify ctDNA mutations.</li> <li class="seamTextUnorderedListItem">Circulating tumor DNA (ctDNA) are small bits of cancer cell DNA that specific tests can find in the bloodstream.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06065748' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.genentechoncology.com/pipeline-molecules/serd-3.html#:~:text=This%20compound%20and%20its%20use,US%20Food%20and%20Drug%20Administration.' target='_blank'>Genentech: Giredestrant Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/what-are-cdk46-inhibitors' target='_blank'>Breastcancer.org: CDK4/6 Inhibitors</a> </li></ul>

NEAREST SITE: 22 miles Contra Costa Regional Medical Center Martinez,CA

NCT ID: NCT03418961

Carvedilol to Prevent Heart Problems in People with Metastatic HER2+ Breast Cancer

Prospective Evaluation of Carvedilol in Prevention of Cardiac Toxicity in Patients With Metastatic HER-2+ Breast Cancer, Phase III Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 3 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Intervention</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Carvedilol, by mouth, daily for up to 2 years</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">No intervention</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3: If you are already taking taking a beta blocker, ARB, or ACE inhibitor</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Observation for up to 2 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Some breast cancer treatments can cause or increase the risk of heart problems, which is called cardiotoxicity. </li> <li class="seamTextUnorderedListItem">The beta-blocker being used in this study is carvedilol. It is used to treat heart failure and high blood pressure.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03418961' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.breastcancer.org/treatment/side_effects/heart_probs' target='_blank'>Breastcancer.org: Heart Problems</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.health.harvard.edu/heart-health/treatments-for-breast-cancer-may-harm-the-heart' target='_blank'>Harvard Health Publishing: Treatments for Breast Cancer</a> </li></ul>

NEAREST SITE: 22 miles Redwood City Redwood City,CA

NCT ID: NCT05059444

ctDNA Test to Detect Breast Cancer That Has Come Back or Remains After Treatment

ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation (ORACLE) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Blood tests</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Circulating tumor DNA (ctDNA) are small pieces of cancer cell DNA in the bloodstream.</li> <li class="seamTextUnorderedListItem">Guardant Reveal is a new test that detects ctDNA in blood.</li> <li class="seamTextUnorderedListItem">Residual disease refers to cancer cells present after treatment.</li> <li class="seamTextUnorderedListItem">Recurrence refers to cancer that has come back after treatment.</li> <li class="seamTextUnorderedListItem">This study is enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05059444' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/genetics/understanding/testing/circulatingtumordna/' target='_blank'>MedLine Plus: What is ctDNA?</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.guardanthealthamea.com/guardant-reveal/' target='_blank'>Guardant Health: The Guardant Reveal ctDNA Test</a> </li></ul>

NCT ID: NCT06112613

Mobile Health Tools to Help Take Medication as Prescribed for People with Metastatic Breast Cancer

Improving Medication Adherence in Metastatic Breast Cancer Using a Connected Customized Treatment Platform (CONCURxP) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Enhanced Usual Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">WiseBag, 1 year</li> <li class="seamTextUnorderedListItem">Educational materials, monthly for 1 year</li> <li class="seamTextUnorderedListItem">Questionnaires, every 3 months for 1 year</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">WiseBag, 1 year</li> <li class="seamTextUnorderedListItem">CONCURxP, 1 year</li> <li class="seamTextUnorderedListItem">Questionnaires, every 3 months for 1 year</li> <li class="seamTextUnorderedListItem">Interviews, 6 months after completing study</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CDK4/6 inhibitors need to be taken as prescribed to receive the best benefit.</li> <li class="seamTextUnorderedListItem">Using WiseBag and CONCURxP may reduce forgetfulness for taking medications.</li> <li class="seamTextUnorderedListItem">WiseBag is a lunch box sized medication monitoring device that holds and monitors medications.</li> <li class="seamTextUnorderedListItem">The CONnected CUstomized Treatment Platform (CONCURxP) includes personalized text message reminders for missed medications, monitoring of the medications you take, and notifications to doctors about missed doses.</li> <li class="seamTextUnorderedListItem">CONCURxP sends a text message when a medication is not taken when it should be.</li> <li class="seamTextUnorderedListItem">This trial is also available in Spanish.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06112613' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/managing-life/staying-on-track-with-treatment' target='_blank'>Breastcancer.org: Following Your Treatment Plan</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/what-are-cdk46-inhibitors' target='_blank'>Breastcancer.org: CDK4/6 Inhibitors</a> </li></ul>

NEAREST SITE: 23 miles John Muir Medical Center-Walnut Creek Walnut Creek,CA

NCT ID: NCT01570998

Targeted Intraoperative Radiotherapy (TARGIT) Registry Trial

Targeted Intraoperative Radiotherapy United States (TARGIT-US) Phase IV Registry Trial: A Registry Trial of Targeted Intraoperative Radiation Therapy Following Breast-conserving Surgery Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Intraoperative radiotherapy as a single dose after breast conserving surgery (lumpectomy)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Participants may receive whole breast radiation, if indicated.</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Radiation is used to kill any breast cancer cells that may not have been removed during surgery.</li> <li class="seamTextUnorderedListItem">Targeted intraoperative radiotherapy is delivered during surgery immediately after the tumor has been removed. This allows the radiation to accurately target the tissue surrounding the tumor, where the risk of recurrence is highest.</li> <li class="seamTextUnorderedListItem">It takes about 20-35 minutes to provide intraoperative radiotherapy.</li> <li class="seamTextUnorderedListItem">The Targeted Intraoperative Radiotherapy Trial (TARGIT), will follow women who receive this type of radiation therapy for five years, allowing researchers to study its effectiveness and side effects.</li> <li class="seamTextUnorderedListItem">If indicated, you will also receive whole breast radiation.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT01570998' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/radiation/intraoperative' target='_blank'>Breastcancer.org: Intraoperative Radiation Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://scholar.google.com/scholar?q=intraoperative+radiation+therapy+breast+cancer&hl=en&as_sdt=0&as_vis=1&oi=scholart&sa=X&ei=V-NpUMOGOObmiwKC2IHQDg&ved=0CCkQgQMwAA' target='_blank'>Google Scholar: Intraoperative Radiation Therapy Breast Cancer</a> </li></ul>

NEAREST SITE: 23 miles Research Site Walnut Creek,CA

NCT ID: NCT05952557

Camizestrant Hormone Therapy for Stage I-III ER+, HER2- Breast Cancer

CAMBRIA-2: A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety of Camizestrant (AZD9833, a Next Generation, Oral Selective Estrogen Receptor Degrader) vs Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) as Adjuvant Treatment for Patients With ER+/HER2- Early Breast Cancer and an Intermediate-High or High Risk... Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Standard of care hormone therapy: Exemestane (Aromasin®), letrozole (Femara®), anastrozole (Arimidex®), or tamoxifen (Nolvadex®)</li> <li class="seamTextUnorderedListItem">With or without: Abemaciclib (Verzenio®), by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Camizestrant (AZD9833), by mouth </li> <li class="seamTextUnorderedListItem">With or without: Abemaciclib (Verzenio®), by mouth</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Camizestrant (AZD9833) is an experimental hormone therapy called a selective estrogen receptor degrader (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®) is a type of targeted therapy called a CDK4/6 inhibitor. CDK4/6 inhibitors block two enzymes, CDK4 and CDK6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">Exemestane (Aromasin®), letrozole (Femara®), and anastrozole (Arimidex®) are types of hormone therapy called aromatase inhibitors. Aromatase inhibitors block some production of estrogen that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Tamoxifen (Nolvadex®) is a type of hormone therapy called a selective estrogen receptor modulator (SERM). SERMs work by blocking the activity of estrogen.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05952557' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.aacr.org/about-the-aacr/newsroom/news-releases/camizestrant-may-be-superior-to-fulvestrant-in-patients-with-hormone-receptor-positive-her2-negative-breast-cancer/' target='_blank'>American Association for Cancer Research: Camizestrant</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/aromatase-inhibitors' target='_blank'>Breastcancer.org: Aromatase Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/verzenio' target='_blank'>Breastcancer.org: Abemaciclib (Verzenio®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/tamoxifen' target='_blank'>Breastcancer.org: Tamoxifen (Nolvadex®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.goodrx.com/conditions/breast-cancer/oral-serd' target='_blank'>GoodRX: What is a SERD?</a> </li></ul>

NEAREST SITE: 27 miles Stanford University School of Medicine Stanford,CA

VISITS: 1 visit

NCT ID: NCT01034033

A Study of How Cancer Develops in Women With BRCA1/2 or Other Genetic Mutations

Genetic & Pathological Studies of BRCA1/BRCA2: Associated Tumors & Blood Samples Scientific Title

• <p class="seamTextPara"> All participants will provide blood samples.</p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BRCA1 and BRCA2 are tumor suppressor genes.</li> <li class="seamTextUnorderedListItem">Inheriting a mutation in the BRCA1 or BRCA2 gene increases cancer risk. </li> <li class="seamTextUnorderedListItem">For the cancer to develop, though, the cells will need to first acquire other mutations.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT01034033' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://stanfordhealthcare.org/medical-conditions/cancer/hboc/brca-1-and-2.html' target='_blank'>Stanford: About Hereditary Breast Ovarian Cancer Syndrome</a> </li><li class='seamTextUnorderedListItem'><a href='https://clinicaltrials.gov/ct2/show/NCT01034033?term=NCT01034033&rank=1' target='_blank'>ClinicalTrials.gov trial info</a> </li></ul>

NEAREST SITE: 27 miles Stanford University Stanford,CA

VISITS: May require hospital stay

NCT ID: NCT04282044

T cell Immunotherapy CRX100 for Advanced Triple Negative Breast Cancer

A Phase 1, Open-Label, Dose-Escalation Study of CRX100 in Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Blood draw to collect white blood cells to make the immunotherapy (leukapheresis)</li> <li class="seamTextUnorderedListItem">CRX100, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">A hospital stay may be required</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CRX100 is the name of the immunotherapy used in this trial. It may work by directly killing cancer cells and by getting the immune system to go after and kill cancer cells. </li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04282044' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.bioeclipse.com/clinical-trials-overview/' target='_blank'>BioEclipse Therapeutics Drug Information Page: CRX1000</a> </li><li class='seamTextUnorderedListItem'><a href='https://pubmed.ncbi.nlm.nih.gov/25381063/' target='_blank'>Journal Article Abstract: Cytokine-Induced Killer (CIK) Cells in Cancer Immunotherapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/breast-cancer-immunotherapy-clinical-trials/' target='_blank'>Metastatic Trial Talk: Immunotherapy & Metastatic Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://en.wikipedia.org/wiki/Leukapheresis' target='_blank'>Wikipedia: Leukapheresis</a> </li></ul>

NCT ID: NCT04300556

Experimental Antibody-Drug Conjugate MORAb-202 for Women with Metastatic Triple Negative Breast Cancer that Tests Positive for FRA

A Multicenter, Open-Label Phase 1/2 Trial Evaluating the Safety, Tolerability, and Efficacy of MORAb-202, a Folate Receptor Alpha (FRα)-Targeting Antibody-drug Conjugate (ADC) in Subjects With Selected Tumor Types Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">MORAb-202, by IV, every 3 weeks, ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells. Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">MORAb-202 is an experimental ADC. </li> <li class="seamTextUnorderedListItem">Its antibody targets FAR, a protein, and it delivers an anti-cancer drug called eribulin mesylate.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling women with other types of cancer. </li> <li class="seamTextUnorderedListItem">Targets or mutations: FRA</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04300556' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Getting to the Target, Antibody-Drug Conjugates</a> </li><li class='seamTextUnorderedListItem'><a href='https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.5544' target='_blank'>Journal Article Abstract: MORAb-202</a> </li></ul>

NCT ID: NCT04756765

Talazoparib PARP Inhibitor for Advanced Breast Cancer with a PALB2 Mutation

A Phase 2 Clinical Trial of Talazoparib Monotherapy for PALB2 Mutation Associated Advanced Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Talazoparib (Talzenna®), by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Talazoparib (Talzenna®) is a type of targeted therapy called a PARP inhibitor. PARP inhibitors work by blocking the action of poly (ADP-ribose) polymerase, an enzyme that helps repair DNA.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04756765' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/talzenna' target='_blank'>Breastcancer.org: Talazoparib (Talzenna®)</a> </li></ul>

NEAREST SITE: 27 miles Stanford Cancer Institute Palo Alto,CA

VISITS: 1 visit per month

NCT ID: NCT05305365

QBS72S Chemotherapy for Metastatic Triple Negative Breast Cancer with Brain or Leptomeningeal Metastasis

A Phase IIa Study Assessing QBS72S For Treating Brain Metastases of Triple Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">QBS72S, by IV, monthly</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">QBS72S is an experimental chemotherapy that may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Leptomeningeal metastasis (LM) is when cancer has spread to the leptomeninges, also called leptomeningeal carcinomatosis, leptomeningeal disease (LMD), leptomeningeal cancer, neoplastic meningitis, meningeal metastasis, and meningeal carcinomatosis, among other names.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05305365' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.quadrigabiosciences.com/science/' target='_blank'>Quadriga Biosciences: QBS72S Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/chemotherapy' target='_blank'>Breastcancer.org: Chemotherapy</a> </li></ul>

NEAREST SITE: 27 miles Stanford University Medical Center Stanford,CA

NCT ID: NCT05514717

XMT-2056 ADC for Advanced HER2+ or HER2 Mutated Breast Cancer

A Phase 1, First in Human, Dose Escalation and Expansion, Multicenter Study of XMT-2056 in Participants With Advanced/Recurrent Solid Tumors That Express HER2 Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">XMT-2056, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">XMT-2056 is an experimental antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">XMT-2056's antibody targets HER2, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called Immunosynthen.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: HER2</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05514717' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mersana.com/pipeline/overview/' target='_blank'>Mersana Therapeutics Drug Information Page: XMT-2056</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mersana.com/our-technology-platforms/about-adcs/' target='_blank'>Mersana Therapeutics: About ADCs</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mersana.com/our-technology-platforms/immunosynthen/' target='_blank'>Mersana Therapeutics: Immunosynthen</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li></ul>

NEAREST SITE: 28 miles Kaiser Permanente - Northern California Vallejo,CA

NCT ID: NCT03061305

Molecular Profiling to Select Treatment for Advanced Breast Cancer

Profiling Biospecimens From Cancer Patients to Screen for Molecular Alterations Related to Treatment Selection (STRATA) Scientific Title

• <p class="seamTextPara"> Molecular profiling will be done on your tumor sample at no cost.</p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">A sample of your tumor will be tested for certain mutations and biomarkers. </li> <li class="seamTextUnorderedListItem">Your doctor will be told if there are treatments or clinical trials available for people with the mutations or biomarkers found in your tumor. </li> <li class="seamTextUnorderedListItem">This trial is also enrolling patients with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03061305' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/symptoms/testing/types/broad-molecular-profiling-tests' target='_blank'>Breastcancer.org: Broad Molecular Profiling Tests</a> </li><li class='seamTextUnorderedListItem'><a href='https://unclineberger.org/research/octr/our-research/strata-trial' target='_blank'>UNC Lineberger Comprehensive Cancer Center: Study website</a> </li></ul>

NEAREST SITE: 28 miles Stanford University Stanford,CA

VISITS: Daily visits for 5 days, followed by surgery

NCT ID: NCT03909282

Radiation Therapy Before Surgery For DCIS

A Randomized Phase II Study Comparing Surgical Excision Versus Neoadjuvant Radiotherapy Followed by Delayed Surgical Excision of Ductal Carcinoma In Situ (NORDIS) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Partial breast irradiation, once a day for 5 days, before surgery</li> <li class="seamTextUnorderedListItem">Lumpectomy or mastectomy</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Lumpectomy or mastectomy</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">This study is looking at the effect radiation therapy has on DCIS cancer cells and surrounding tissue when it is given before surgery.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03909282' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/symptoms/types/dcis/treatment?gclid=EAIaIQobChMIyOnukvrn5QIVoxx9Ch1_pgdEEAAYAiAAEgIxZvD_BwE' target='_blank'>Breastcancer.org: Treatment for DCIS</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/research-news/rads-after-sx-for-dcis-reduces-recurrence-risk' target='_blank'>Breastcancer.org: Radiation Therapy After Surgery for Low-Risk DCIS Reduces Recurrence Risk</a> </li></ul>

NEAREST SITE: 28 miles Stanford University Palo Alto,CA

VISITS: 1 visit per week, ongoing

NCT ID: NCT04092673

eFT226 in Advanced Breast Cancer That Tests Positive for HER2, ERBB3, FGFR1, FGFR2, or KRAS Mutations

A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">eFT226 (Zotatifin), by IV, weekly, ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">eFT226 (Zotatifin) is an experimental targeted therapy that blocks eIF4A1. </li> <li class="seamTextUnorderedListItem">This study also is enrolling patients with other types of solid tumors that have these mutations.</li> <li class="seamTextUnorderedListItem">Targets or mutations: HER2 (ERBB2), ERBB3, FGFR1, FGFR2, or KRAS</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04092673' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.globenewswire.com/news-release/2019/11/05/1941103/0/en/eFFECTOR-Therapeutics-Initiates-Phase-1-2-Safety-and-Efficacy-Study-of-Zotatifin-eFT226-in-Patients-with-Advanced-Solid-Tumor-Malignancies.html' target='_blank'>Drug Company Press Release: eFT226 (Zotatifin)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.org/cancer/breast-cancer/treatment/targeted-therapy-for-breast-cancer.html' target='_blank'>American Cancer Society: Targeted Therapies for Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.nature.com/articles/cddis2014542' target='_blank'>Journal Article: The Malignant Phenotype in Breast Cancer is Driven by eIF4A1-mediated Changes in The Translational Landscape</a> </li></ul>

NEAREST SITE: 28 miles Kaiser Permanente - Vallejo Vallejo,CA

NCT ID: NCT04961996

Giredestrant Adjuvant Therapy for Stage I-III ER+, HER2- Breast Cancer

A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Patients With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Giredestrant, by mouth, daily for 5 years</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard Treatment</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Physician's choice of aromatase inhibitor or tamoxifen, by mouth, daily for 5 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Adjuvant therapy is treatment given after surgery for stage I, stage II, or stage III breast cancer to prevent cancer from returning.</li> <li class="seamTextUnorderedListItem">Giredestrant is an experimental hormone therapy called a SERD (selective estrogen receptor degrader). SERDs work by binding to and breaking down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®) are types of hormone therapy called aromatase inhibitors. Aromatase inhibitors block some production of estrogen that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Tamoxifen (Nolvadex®) is a type of hormone therapy called a selective estrogen receptor modulator (SERM). SERMs work by blocking the activity of estrogen.</li> <li class="seamTextUnorderedListItem">Tamoxifen (Nolvadex®) is commonly used to treat hormone-sensitive breast cancer.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women and men will also be given a drug that will put women in temporary menopause.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04961996' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.genentechoncology.com/pipeline-molecules/serd-3.html' target='_blank'>Genentech Drug Information Page: Giredestrant</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy' target='_blank'>Breastcancer.org: Hormone Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/tamoxifen' target='_blank'>Breastcancer.org: Tamoxifen (Nolvadex®)</a> </li></ul>

NEAREST SITE: 28 miles Stanford Cancer Institute Palo Alto,CA

NCT ID: NCT05082610

HMBD-002 Immunotherapy with Pembrolizumab for Advanced Triple Negative Breast Cancer

A Phase 1 Study of HMBD-002-V4C26 (HMBD-002), a Monoclonal Antibody Targeting VISTA, as Monotherapy and Combined With Pembrolizumab, in Patients With Advanced Solid Malignancies Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">HMBD-002, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">HMBD-002, by IV</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">HMBD-002 is an experimental immunotherapy that targets a protein called VISTA and may increase the immune system's ability to kill cancer cells.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05082610' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://hummingbirdbioscience.com/hmbd-002/' target='_blank'>Hummingbird Bioscience: HMBD-002 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.precisiononcologynews.com/cancer/hummingbird-bioscience-merck-study-hmbd-002-keytruda-various-solid-tumors' target='_blank'>Precision Oncology News: HMBD-002</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/immune-checkpoint-inhibitor/' target='_blank'>Metastatic Trial Talk: Update on Immunotherapy for MBC: Immune Checkpoint Inhibitors</a> </li></ul>

NEAREST SITE: 28 miles Stanford Cancer Institute Palo Alto Palo Alto,CA

VISITS: 2 visits within 1 month including surgery; may require hospitalization

NCT ID: NCT05438212

Radiation Before or After Surgery for Brain Metastasis

A Randomized Phase III Trial of Pre-Operative Compared to Post-Operative Stereotactic Radiosurgery in Patients With Resectable Brain Metastases Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Brain surgery to remove brain tumor</li> </ul> <p class="seamTextPara"> followed 10-30 days later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiosurgery, 1 time</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiosurgery, 1 time</li> </ul> <p class="seamTextPara"> followed up to 7 days later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Brain surgery to remove brain tumor</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiosurgery is a type of radiation therapy that delivers a high dose of radiation only to the small areas of cancer in the brain and avoids the surrounding normal brain tissue.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05438212' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li></ul>

NEAREST SITE: 28 miles Kaiser Permanente Medical Center - Vallejo Vallejo,CA

VISITS: 1-3 visits per month

NCT ID: NCT05501886

Gedatolisib pan-PI3K/mTOR Inhibitor for Advanced HR+, HER2- Breast Cancer

Phase 3, Open-Label, Randomized, Study Comparing Gedatolisib Combined With Fulvestrant & With or Without Palbociclib to Standard-of-Care Therapies in Patients With HR-Positive, HER2-Negative Advanced Breast Cancer Previously Treated With a CDK4/6 Inhibitor in Combination w/Non-Steroidal Aromatase Inhibitor Therapy Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 4 groups depending on your cancer: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental, with or without PIK3CA Mutation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Gedatolisib, by IV, weekly, 3 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), by mouth, daily, 3 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, every 2 weeks for 1 month, then monthly</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Experimental, with or without PIK3CA Mutation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Gedatolisib, by IV, weekly, 3 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, every 2 weeks for 1 month, then monthly</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3: Standard of Care, without PIK3CA Mutation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, every 2 weeks for 1 month, then monthly</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 4: Standard of Care, with PIK3CA Mutation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®), by mouth, daily</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, every 2 weeks for 1 month, then monthly</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Gedatolisib is an experimental targeted therapy called a pan-PI3K/mTOR inhibitor. Blocking PI3K and mTOR may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®) is a type of targeted therapy called a CDK 4/6 inhibitor. CDK 4/6 inhibitors block two enzymes, CDK 4 and CDK 6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor downregulator (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®) is a type of targeted therapy called a PI3K inhibitor. Blocking the PI3K pathway may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women will also be given a drug that will put women in temporary menopause.</li> <li class="seamTextUnorderedListItem">Targets or mutations: PIK3CA</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05501886' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.celcuity.com/gedatolisib/' target='_blank'>Celcuity Drug Information Page: Gedatolisib</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/ibrance' target='_blank'>Breastcancer.org: Palbociclib (Ibrance®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/piqray' target='_blank'>Breastcancer.org: Alpelisib (Piqray®)</a> </li></ul>

NEAREST SITE: 28 miles Stanford Hospital and Clinics Palo Alto,CA

NCT ID: NCT05975359

Comparing Drains During Bilateral Mastectomy with Immediate Breast Reconstruction

A Pilot Study of the Interi Manifold With Traditional Surgical Drains in Implant-Based Breast Reconstruction Scientific Title

• <p class="seamTextPara"> You will receive the following during surgery: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Interi Drain on 1 breast</li> <li class="seamTextUnorderedListItem">Jackson-Pratt (JP) Drain on 1 breast</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Drain log, daily</li> <li class="seamTextUnorderedListItem">Drain removal, 1-3 weeks after surgery</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">During implant-based breast reconstruction, surgical drains are placed to prevent fluid build up.</li> <li class="seamTextUnorderedListItem">The most frequently used drain is a Jackson-Pratt (JP) Drain.</li> <li class="seamTextUnorderedListItem">The Interi Drain system may work better than the JP Drain system.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05975359' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 40 miles Providence Queen of the Valley Medical Center Napa,CA

NCT ID: NCT05654623

ARV-471 Hormone Therapy Compared to Fulvestrant Hormone Therapy for Advanced ER+, HER2- Breast Cancer

A PHASE 3, RANDOMIZED, OPEN-LABEL, MULTICENTER TRIAL OF ARV-471 (PF-07850327) VS FULVESTRANT IN PARTICIPANTS WITH ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE ADVANCED BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR ENDOCRINE BASED TREATMENT FOR ADVANCED DISEASE (VERITAC-2) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ARV-471 (PF-07850327), by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, every 2 weeks for 1 month, then monthly</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ARV-471 (PF-07850327) is an experimental hormone therapy called a PROTAC protein degrader that breaks down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor degrader (SERD). SERDs bind to and break down estrogen receptors.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05654623' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='www.veritac2study.com' target='_blank'>Pfizer: Study Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.arvinas.com/pipeline-programs/estrogen-receptor' target='_blank'>Arvinas: ARV-471 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li></ul>

NEAREST SITE: 47 miles Sutter Cancer Centers Radiation Oncology Services-Vacaville Vacaville,CA

NCT ID: NCT04266249

Neoadjuvant (Before Surgery) Chemotherapy and Targeted Therapies for Stage II-III, HER2+ Breast Cancer

(CompassHER2-pCR): Preoperative THP and Postoperative HP in Patients Who Achieve a Pathologic Complete Response (EA1181) Scientific Title

• <p class="seamTextPara"> Before surgery, you will receive the following, for 3 months: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Chemotherapy, by IV, either once a week or every 3 weeks</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®), by IV, every week (3 weeks on, 1 week off)</li> <li class="seamTextUnorderedListItem">Pertuzumab (Perjeta®), by IV, once every 3 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Followed by surgery (lumpectomy or mastectomy)</i> </p> <p class="seamTextPara"> After surgery, you will be assigned to 1 of 2 groups depending upon if you had any tumor remaining: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: No tumor remaining</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®), by IV, once every 3 weeks, for 6 months</li> <li class="seamTextUnorderedListItem">Pertuzumab, (Perjeta®), by IV, once every 3 weeks, for 6 months</li> <li class="seamTextUnorderedListItem">Radiation therapy and/or hormone therapy</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Tumor remaining</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab emtansine/T-DM1 (Kadcyla®), by IV, for 10 months</li> <li class="seamTextUnorderedListItem">Radiation therapy, hormone therapy and/or chemotherapy</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Neoadjuvant chemotherapy and targeted therapy (treatment given before surgery) is used to shrink tumors.</li> <li class="seamTextUnorderedListItem">Sometimes the tumor will disappear completely and sometimes there will still be some tumor remaining at the time of surgery. </li> <li class="seamTextUnorderedListItem">Your doctor will decide which neoadjuvant chemotherapy to give you: docetaxel (Taxotere®), nab-paclitaxel (Abraxane®), or paclitaxel (Taxol®). </li> <li class="seamTextUnorderedListItem">Everyone will receive the same anti-HER2 targeted therapies of trastuzumab (Herceptin®) and pertuzumab (Perjeta®).</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04266249' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://ecog-acrin.org/clinical-trials/ea1181-educational-materials' target='_blank'>Cancer Research Group: CompassHER2 Website</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.healthline.com/health/breast-cancer/chemotherapy-for-her2-positive-breast-cancer#chemotherapy-side-effects' target='_blank'>Healthline: Chemotherapy and Targeted Therapy for HER2-Positive Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/symptoms/diagnosis/her2' target='_blank'>Breastcancer.org: HER2 Status</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.hematologyandoncology.net/archives/may-2019/how-we-treat-locally-advanced-her2-positive-breast-cancer/' target='_blank'>Clinical Advances in Hematology & Oncology: How We Treat Locally Advanced HER2-Positive Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://esmoopen.bmj.com/content/4/3/e000515' target='_blank'>Journal Article: Neoadjuvant Treatment for Intermediate/High-Risk HER2 Positive and Triple Negative Breast Cancers</a> </li></ul>

NEAREST SITE: 53 miles Research Site Santa Rosa,CA

NCT ID: NCT05123482

AZD8205 for Advanced Triple Negative BreastCancer

A Phase I/IIa Multi-center, Open-label Master Protocol to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Antitumor Activity of AZD8205 in Participants With Advanced or Metastatic Solid Malignancies Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">AZD8205, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule.</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05123482' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 53 miles St. Jude Hospital Yorba dba St. Joseph Heritage Healthcare Santa Rosa,CA

VISITS: 1 visit every 2-3 weeks

NCT ID: NCT05382286

Sacituzumab Govitecan-hziy ADC and Pembrolizumab for Advanced PD-L1 Positive, Triple Negative Breast Cancer

A Randomized, Open-label, Phase 3 Study of Sacituzumab Govitecan and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer, Whose Tumors Express PD-L1 (ASCENT-04) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: ADC with Immunotherapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Sacituzumab govitecan (Trodelvy®), by IV, weekly, 2 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Chemotherapy with Immunotherapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®) or nab-paclitaxel (Abraxane®), by IV, weekly, 3 weeks on, 1 week off</li> </ul> <p class="seamTextPara"> or </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Gemcitabine (Gemzar®) with carboplatin (Paraplatin®), by IV, weekly, 2 weeks on, 1 week off</li> </ul> <p class="seamTextPara"> with: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">May require 1 biopsy</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Sacituzumab govitecan (Trodelvy®) is a type of targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">The antibody in sacituzumab govitecan (Trodelvy®) targets TROP2 proteins. It delivers the chemotherapy irinotecan.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is an experimental type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), nab-paclitaxel (Abraxane®), gemcitabine (Gemzar®), and carboplatin (Paraplatin®) are chemotherapy drugs.</li> <li class="seamTextUnorderedListItem">Targets or mutations: PD-L1</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05382286' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/trodelvy#:~:text=Trodelvy%20(chemical%20name%3A%20sacituzumab%20govitecan,two%20or%20more%20systemic%20therapies.' target='_blank'>Breastcancer.org: Sacituzumab govitecan-hziy (Trodelvy®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Antibody-Drug Conjugates (ADC)</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/immune-checkpoint-inhibitor/' target='_blank'>Metastatic Trial Talk: Update on Immunotherapy for MBC: Immune Checkpoint Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://tnbcfoundation.org/' target='_blank'>Triple Negative Breast Cancer Foundation: Home</a> </li></ul>

NEAREST SITE: 53 miles Providence Medical Foundation Santa Rosa,CA

NCT ID: NCT05579366

PRO1184 Antibody Drug Conjugate for Advanced HER2- Breast Cancer that Expresses FRA

Phase 1/2 Study of PRO1184 in Patients With Locally Advanced and/or Metastatic Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PRO1184, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PRO1184 is an experimental antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">BB-1701's antibody targets folate receptor alpha (FRA), a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called exatecan.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: FRA</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05579366' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.prnewswire.com/news-releases/profoundbio-receives-fda-study-may-proceed-letter-for-pro1184-a-folate-receptor-alpha-directed-adc-with-a-topoisomerase-1-inhibitor-payload-and-welcomes-naomi-hunder-md-as-chief-medical-officer-301598943.html?tc=em' target='_blank'>ProfoundBio Press Release: PRO1184</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li></ul>

NEAREST SITE: 53 miles Providence Medical Foundation - Santa Rosa, CA Santa Rosa,CA

NCT ID: NCT05696626

Lasofoxifene Hormone Therapy with CDK4/6 Inhibitor for Advanced ER+, HER2- Breast Cancer With an ESR1 Mutation

An Open Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of the Combination of Lasofoxifene and Abemaciclib to the Combination of Fulvestrant and Abemaciclib for the Treatment of Pre- and Postmenopausal Women and Men With Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (ELAINEIII) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Lasofoxifene, by mouth, daily</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, 2 times in 1 month, then monthly</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Lasofoxifene is an experimental hormone therapy called a selective estrogen receptor modulator (SERM). SERMs work by blocking the activity of estrogen.</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®) is a type of targeted therapy called a CDK4/6 inhibitor. It blocks two enzymes, CDK4 and CDK6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor downregulator (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Targets or mutations: ESR1</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05696626' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://sermonixpharma.com/lasofoxifene/' target='_blank'>Sermonix Pharmaceuticals: Lasofoxifene Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/verzenio' target='_blank'>Breastcancer.org: Abemaciclib (Verzenio®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li></ul>

NCT ID: NCT06103864

Dato-DXd ADC With or Without Durvalumab Immunotherapy for Advanced Triple Negative, PD-L1 Positive Breast Cancer

A Phase III, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy (Paclitaxel, Nab-paclitaxel or Gemcitabine + Carboplatin) in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast (TROPION-Breast05) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 3 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Datopotamab deruxtecan (Dato-DXd), by IV</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®), by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Standard of care chemotherapy</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Datopotamab deruxtecan (Dato-DXd), by IV</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Datopotamab deruxtecan (Dato-DXd) is an experimental antibody-drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Datopotamab deruxtecan's antibody targets TROP2, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called deruxtecan.</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®) and pembrolizumab (Keytruda®) are a type of immunotherapy called PD-1 inhibitors, which are a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">In this trial, standard of care chemotherapy drugs include carboplatin (Paraplatin®), paclitaxel (Taxol®), nab-paclitaxel (Abraxane®), and/or gemcitabine (Gemzar®).</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06103864' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.astrazenecaclinicaltrials.com/study/D7630C00001/' target='_blank'>AstraZeneca: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://ascopost.com/issues/october-10-2022-supplement-breast-cancer-almanac/datopotamab-deruxtecan-shows-activity-in-advanced-triple-negative-breast-cancer/' target='_blank'>ASCO: Datopotamab Deruxtecan (Dato-DXd)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancertherapyadvisor.com/home/news/conference-coverage/asco-2021/asco-2021-breast-cancer-in-depth/breast-cancer-durvalumab-neoadjuvant-chemo-treatment-risk/#:~:text=June%2024%2C%202021-,Durvalumab%20Improves%20Survival%20When%20Added%20to,in%2' target='_blank'>Cancer Therapy Advisor: Durvalumab (Imfinzi®)</a> </li></ul>

NEAREST SITE: 74 miles University of California Davis Comprehensive Cancer Center Sacramento,CA

VISITS: Number of visits varies, ongoing

NCT ID: NCT03606967

Chemotherapy & Immunotherapy With or Without A Personalized Vaccine for Metastatic Triple Negative Breast Cancer That Is PD-L1 Negative

Randomized Phase 2 Clinical Trial of Nab-Paclitaxel + MEDI4736 (Durvalumab) + Tremelimumab + Neoantigen Vaccine vs. Nab-Paclitaxel + MEDI4736 (Durvalumab) + Tremelimumab in Patients With Metastatic Triple Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Vaccine</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Gemcitabine (Gemzar®) and carboplatin (Paraplatin®), by IV, every week (2 weeks on, 1 week off), for 4.5 months</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Personalized SLP Vaccine and Hiltonol® (poly-ICLC), 7 times over 2.5 months</li> <li class="seamTextUnorderedListItem">Tremelimumab, by IV, once a month, for 4 months</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®), by IV, once a month, ongoing</li> <li class="seamTextUnorderedListItem">Nab-paclitaxel (Abraxane®), by IV, every week (3 weeks on, 1 week off), ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: No Vaccine</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Gemcitabine (Gemzar®) and carboplatin (Paraplatin®), by IV, every week (2 weeks on, 1 week off), for 4.5 months</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Tremelimumab, by IV, once a month, for 4 months</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®), by IV, once a month, ongoing</li> <li class="seamTextUnorderedListItem">Nab-paclitaxel (Abraxane®), by IV, every week (3 weeks on, 1 week off), ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The type of vaccine used in this trial is called a personalized synthetic long peptide (SLP) vaccine. It may help your immune system see and fight cancer cells. </li> <li class="seamTextUnorderedListItem">Hiltonol® (poly-ICLC) is an immune cell activating factor.</li> <li class="seamTextUnorderedListItem">Carboplatin (Paraplatin®) is a chemotherapy routinely used to treat advanced and metastatic triple negative breast cancer.</li> <li class="seamTextUnorderedListItem">Gemcitabine (Gemzar®) is a chemotherapy used to treat breast cancer.</li> <li class="seamTextUnorderedListItem">Tremelimumab is a type of immunotherapy called a CTLA-4 inhibitor.</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®) is a type of immunotherapy called a PD-L1 (programmed cell death ligand-1) inhibitor. It works by stimulating the body's immune system to go after cancer cells. It has been approved to treat certain types of cancers, but its use in breast cancer is considered experimental.</li> <li class="seamTextUnorderedListItem">Nab-paclitaxel (Abraxane®) is a chemotherapy approved to treat advanced breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03606967' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/inside-clinical-trials/breast-cancer-treatment-vaccines/' target='_blank'>Metastatic Trial Talk: Breast Cancer Treatment Vaccines</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/search/Personalized%20Synthetic%20Long%20Pe/?searchMode=Begins' target='_blank'>NCI Drug Dictionary: Personalized Synthetic Long Peptide Breast Cancer Vaccine</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.oncovir.com' target='_blank'>Oncovir Drug Information Page: Hiltonol® (poly-ICLC)</a> </li><li class='seamTextUnorderedListItem'><a href='https://en.wikipedia.org/wiki/Tremelimumab' target='_blank'>Wikipedia: Tremelimumab</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-terms/def/durvalumab' target='_blank'>NCI Drug Dictionary: Durvalumab (Imfinzi®)</a> </li></ul>

NEAREST SITE: 74 miles University of California Davis Sacramento,CA

NCT ID: NCT05208762

SGN-PDL1V Antibody Drug Conjugate for Advanced Triple Negative Breast Cancer

A Phase 1 Study of SGN-PDL1V in Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">SGN-PDL1V, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">SGN-PDL1V is an experimental antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Its antibody targets PD-1/PD-L1, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called vedotin.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05208762' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.clinicaltrials.seagen.com/study/?pid=SGNPDL1V-001' target='_blank'>Seagen Trial Information Page: SGN-PDL1V</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li><li class='seamTextUnorderedListItem'><a href='https://investor.seagen.com/press-releases/news-details/2021/Seagen-to-Highlight-Two-Novel-Antibody-Drug-Conjugates-ADCs-at-the-SITC-36th-Annual-Meeting/default.aspx' target='_blank'>Seagen Press Release: SGN-PDL1V</a> </li></ul>

NEAREST SITE: 74 miles University of California, Davis Sacramento,CA

NCT ID: NCT06103669

Adding Radiation to Treatment for People with Metastatic Oligoprogressive Breast Cancer

Locally ablatiVe therApy in oLigO-pRogressive sOlid tUmorS (VALOROUS) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiation or interventional radiology ablation</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Radiation therapy uses high-energy x-rays to damage cancer cell DNA. These x-rays stop cancer cells from dividing and growing, thus slowing or stopping tumor growth.</li> <li class="seamTextUnorderedListItem">Interventional radiology ablation uses heat or cold to kill cancer cells.</li> <li class="seamTextUnorderedListItem">Stereotactic radiation (stereotactic radiosurgery) delivers high-dose, precisely-targeted radiation in fewer doses than traditional radiation therapy.</li> <li class="seamTextUnorderedListItem">Oligoprogressive disease refers to progression of only a few sites of metastasis.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06103669' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://studypages.com/en/s/a-study-of-ablative-therapy-in-people-with-progressive-solid-tumors-valorous-278307/?ref=gallery' target='_blank'>University of California, Davis: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/radiation-therapy' target='_blank'>Breastcancer.org: Radiation Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.columbiaradiology.org/patients/services/interventional-radiology/tumor-ablation' target='_blank'>Columbia University: Interventional Radiology Ablation</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancerresearchuk.org/about-cancer/treatment/radiotherapy/external/types/stereotactic-body-radiotherapy-sbrt' target='_blank'>Cancer Research UK: Stereotactic Radiotherapy</a> </li></ul>

NEAREST SITE: 75 miles Sutter Medical Center Sacramento Sacramento,CA

NCT ID: NCT04588246

Stereotactic Radiotherapy Alone or with Whole Brain Radiotherapy (Excluding the Hippocampus) & a Dementia Medication for Brain Mets that Returned After Stereotactic Radiotherapy

Phase III Trial of Salvage Stereotactic Radiosurgery (SRS) or SRS + Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for First or Second Distant Brain Relapse After Upfront SRS With Brain Metastasis Velocity >/= 4 Brain Metastases/Year Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Memantine, by mouth, once or twice a day, for 6 months</li> <li class="seamTextUnorderedListItem">Whole brain radiation therapy, 10 times over 2 weeks</li> <li class="seamTextUnorderedListItem">folowed by, stereotactic radiotherapy</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiotherapy</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Radiation therapy uses high-energy x-rays to kill tumor cells that remain after surgery.</li> <li class="seamTextUnorderedListItem">Whole brain radiation therapy (WBR) typically targets the entire brain, including the hippocampus. By avoiding the hippocampus, researchers hope to lessen the side effects of WBR. </li> <li class="seamTextUnorderedListItem">Stereotactic radiation (also called stereotactic radiosurgery) delivers focused radiation to each metastasis (met/tumor). </li> <li class="seamTextUnorderedListItem">Memantine is a medication approved for use in people with dementia, but its use in breast cancer is considered experimental. </li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer that have spread to the brain.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04588246' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/news-events/cancer-currents-blog/2018/brain-metastases-radiation-therapy-hippocampal-avoidance' target='_blank'>NCI Cancer Currents Blog: Tailored Radiation to Treat Brain Metastases Reduces Impact on Cognitive Function</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/from-the-experts/side-effects-of-brain-mets-radiation/' target='_blank'>Metastatic Trial Talk: Side Effects of Radiation Therapy to the Brain</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a604006.html' target='_blank'>MedLinePlus: Memantine</a> </li></ul>

NEAREST SITE: 164 miles Community Cancer Institute Clovis,CA

NCT ID: NCT04895709

BMS-986340 Immunotherapy for Advanced Breast Cancer

A Phase 1/2 Study of BMS-986340 as Monotherapy and in Combination With Nivolumab or Docetaxel in Participants With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BMS-986340</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BMS-986340</li> <li class="seamTextUnorderedListItem">Nivolumab (Opdivo®)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BMS-986340 is an experimental immunotherapy called a CCR8 inhibitor. BMS-986340 blocks the activity of CCR8 on immune cells to activate the immune system to go after and kill cancer cells.</li> <li class="seamTextUnorderedListItem">Nivolumab (Opdivo®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04895709' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.bolderscience.com/trial/NCT04895709/' target='_blank'>Bristol-Myers Squibb: Clinical Trial Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.bmsscience.com/?s=BMS-986340+%26plusmn%3B+Nivolumab&search_cat=bms' target='_blank'>Bristol-Myers Squibb: BMS-986340 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.bms.com/assets/bms/us/en-us/pdf/CCR8-Immune-Pathway-Fact-Sheet.pdf' target='_blank'>Bristol-Myers Squibb: CCR8 Immune Pathway</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/anti-ccr8-monoclonal-antibody-bms-986340?redirect=true' target='_blank'>National Cancer Institute: BMS-986340 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://chemocare.com/chemotherapy/drug-info/opdivo.aspx' target='_blank'>Chemocare: Nivolumab (Opdivo®)</a> </li></ul>

NEAREST SITE: 171 miles Carson Tahoe Regional Medical Center Carson City,NV

NCT ID: NCT04314401

NCI Cancer Moonshot Biobank for Stage III-IV Breast Cancer

Cancer Moonshot Biobank Research Protocol Scientific Title

• <p class="seamTextPara"> You will provide the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Tissue and blood samples before, during, and after treatment</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Collecting tissue samples, blood samples, and medical information over time may help researchers better understand resistance to treatment, changes in genes, and other factors about how cancer responds to treatment.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04314401' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://moonshotbiobank.cancer.gov/' target='_blank'>National Cancer Institute: Cancer Moonshot Biobank</a> </li></ul>

NEAREST SITE: 182 miles Cancer Care Specialists Reno,NV

NCT ID: NCT06105632

PF-07220060 CDK4 Inhibitor with Fulvestrant Hormone Therapy for Advanced HR+, HER2- Breast Cancer

AN INTERVENTIONAL, OPEN-LABEL, RANDOMIZED, MULTICENTER PHASE 3 STUDY OF PF-07220060 PLUS FULVESTRANT COMPARED TO INVESTIGATOR'S CHOICE OF THERAPY IN PARTICIPANTS OVER 18 YEARS OF AGE WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE ADVANCED/METASTATIC BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR CDK 4/6 INHIBITOR-BASED THERAPY Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PF-07220060, by mouth, daily</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection</li> </ul> <p class="seamTextPara"> or </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Everolimus (Afinitor®) and exemestane (Aromasin®), by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PF-07220060 is an experimental targeted therapy called a CDK4 inhibitor. CDK4 is a protein that helps cancer grow. Blocking CDK4 helps slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor downregulator (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Everolimus (Afinitor®) is a type of targeted therapy called a mTOR inhibitor. mTOR inhibitors work by interfering with the ability of cancer cells to divide and grow.</li> <li class="seamTextUnorderedListItem">Exemestane (Aromasin®) is a type of hormone therapy called an aromatase inhibitor. Aromatase inhibitors block some production of estrogen that helps cancer grow.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06105632' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.pfizerclinicaltrials.com/find-a-trial/nct06105632-advanced-or-metastatic-breast-cancer-trial' target='_blank'>Pfizer: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://cdn.pfizer.com/pfizercom/product-pipeline/Pipeline_Update_04MAY2021.pdf?VersionId=.06Q_HtLdkBW8lme0Y3EXpraBpgGspyg' target='_blank'>Pfizer: PF-07220060 Drug Information Page</a> </li></ul>

NEAREST SITE: 186 miles Renown Oncology Reno,NV

NCT ID: NCT06157892

Disitamab Vedotin Antibody Drug Conjugate for Advanced HER2 Low or HER2+ Breast Cancer

A Phase 1b/2 Open-Label Study of Disitamab Vedotin Monotherapy or in Combination With Other Anticancer Therapies in Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Disitamab vedotin</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Disitamab vedotin</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Disitamab vedotin is an experimental antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody targets cancer cells, the ADC does minimal damage to normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">The antibody in disitamab vedotin targets HER2 proteins. It delivers the chemotherapy MMAE.</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®) is a type of targeted therapy called a tyrosine kinase inhibitor. It blocks an enzyme, tyrosine kinase, that helps cancer cells grow.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+ or IHC 2+/ISH-.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06157892' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.seagen.com/science/technologies' target='_blank'>Pfizer: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.seagen.com/science/technologies' target='_blank'>Seagen: ADC Information Page</a> </li></ul>

NEAREST SITE: 198 miles University of California Los Angeles - Jonsson Comprehensive Cancer Center,892 Aerovista Place, Suite 240 San Luis Obispo,CA

NCT ID: NCT05382299

Sacituzumab Govitecan-hziy ADC for Advanced Triple Negative Breast Cancer

A Randomized, Open-label, Phase 3 Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Patients With Previously Untreated, Locally Advanced, Inoperable or Metastatic Triple-Negative Breast Cancer Whose Tumors Do Not Express PD-L1 or in Patients Previously Treated With Anti-PD-(L)1 Agents in the Early Setting Whose Tumors Do E... (ASCENT-03) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Sacituzumab govitecan (Trodelvy®), by IV, weekly, 2 weeks on, 1 week off</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®) or nab-paclitaxel (Abraxane®), by IV, weekly, 3 weeks on, 1 week off</li> </ul> <p class="seamTextPara"> or </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Gemcitabine (Gemzar®) with carboplatin (Paraplatin®), by IV, weekly, 2 weeks on, 1 week off</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">May require 1 biopsy</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Sacituzumab govitecan (Trodelvy®) is a type of targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">The antibody in sacituzumab govitecan (Trodelvy®) targets TROP2 proteins. It delivers the chemotherapy irinotecan.</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), nab-paclitaxel (Abraxane®), gemcitabine (Gemzar®), and carboplatin (Paraplatin®) are chemotherapy drugs.</li> <li class="seamTextUnorderedListItem">Targets or mutations: PD-L1</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05382299' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/trodelvy#:~:text=Trodelvy%20(chemical%20name%3A%20sacituzumab%20govitecan,two%20or%20more%20systemic%20therapies.' target='_blank'>Breastcancer.org: Sacituzumab govitecan-hziy (Trodelvy®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/chemotherapy' target='_blank'>Breastcancer.org: Chemotherapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Antibody-Drug Conjugates (ADC)</a> </li><li class='seamTextUnorderedListItem'><a href='https://tnbcfoundation.org/' target='_blank'>Triple Negative Breast Cancer Foundation: Home</a> </li></ul>

NEAREST SITE: 210 miles PCR Oncology Arroyo Grande,CA

NCT ID: NCT05554354

Fulvestrant Alone or With Binimetinib Targeted Therapy for Metastatic HR+, HER2- Breast Cancer with a NF1 Mutation

A ComboMATCH Treatment Trial EAY191-N2: Phase 2 Trial of Fulvestrant and Binimetinib in Patients With Hormone Receptor-Positive Metastatic Breast Cancer With a Frameshift or Nonsense Mutation or Genomic Deletion in NF1 Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection</li> <li class="seamTextUnorderedListItem">Binimetinib (Mektovi®), by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CT, MRI, or bone scan, 2 times</li> <li class="seamTextUnorderedListItem">Biopsy, 2 times</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor degrader (SERD). SERDs bind to and break down estrogen receptors, which may inhibit the growth of estrogen-sensitive tumor cells.</li> <li class="seamTextUnorderedListItem">Binimetinib (Mektovi®) is a type of targeted therapy called a MEK inhibitor that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.</li> <li class="seamTextUnorderedListItem">Targets or mutations: NF1</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05554354' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a618041.html' target='_blank'>Medline Plus: Binimetinib (Mektovi®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex#:~:text=Faslodex%20(chemical%20name%3A%20fulvestrant),%2C%20HER2%2Dnegative%20breast%20cancer.' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li></ul>

NEAREST SITE: 250 miles Research Site Bakersfield,CA

VISITS: 1 visit every 1-3 weeks for 1 year

NCT ID: NCT06112379

Dato-DXd ADC and Immunotherapy Before Surgery for Stage II-III Triple Negative or HR Low, HER2- Breast Cancer

A Phase III, Open-label, Randomised Study of Neoadjuvant Datopotamab Deruxtecan (Dato-DXd) Plus Durvalumab Followed by Adjuvant Durvalumab With or Without Chemotherapy Versus Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Pembrolizumab With or Without Chemotherapy for the Treatment of Adult Patients With Previously Untreated Tr... Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Datopotamab deruxtecan (Dato-DXd), by IV, every 3 weeks, for 6 months before surgery</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®), by IV, every 3 weeks, for 6 months before surgery</li> </ul> <p class="seamTextPara"> followed by (after surgery): </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®), by IV, every 3 weeks for 7 months</li> <li class="seamTextUnorderedListItem">Chemotherapy (if residual disease is found)</li> <li class="seamTextUnorderedListItem">Olaparib (Lynparza®), by mouth (if applicable)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks, before surgery</li> <li class="seamTextUnorderedListItem">Chemotherapy, before surgery</li> </ul> <p class="seamTextPara"> followed by (after surgery): </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks for 7 months</li> <li class="seamTextUnorderedListItem">Chemotherapy (if residual disease is found)</li> <li class="seamTextUnorderedListItem">Olaparib (Lynparza®), by mouth (if applicable)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Datopotamab deruxtecan (Dato-DXd) is an experimental antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody drug conjugate (ADC) combines an antibody that targets cancer cells with a therapy that kills cancer cells.</li> <li class="seamTextUnorderedListItem">Because it only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Dato-DXd's antibody targets TROP2, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called deruxtecan.</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®) and pembrolizumab (Keytruda®) are types of immunotherapy called PD-L1 inhibitors, which are a type of immune checkpoint inhibitor. Blocking PD-L1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">Olaparib (Lynparza®) is a targeted therapy called a PARP inhibitor, which work by blocking the action of an enzyme that helps repair DNA. It will be given to people with residual disease and BRCA positive (BRCA+) tumors.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06112379' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.astrazeneca.com/our-therapy-areas/pipeline.html#oncology' target='_blank'>AstraZeneca: Datopotamab Deruxtecan (Dato-DXd) Drug Information Page</a> </li></ul>

NEAREST SITE: 273 miles Research Site Santa Barbara,CA

VISITS: 1 visit every 1-3 weeks

NCT ID: NCT06018337

DB-1303/BNT323 Antibody Drug Conjugate for Advanced HR+, HER2 Low Breast Cancer

A Phase 3, Randomized, Multi-center, Open-Label Study of DB-1303 Versus Investigator's Choice Chemotherapy in Human Epidermal Growth Factor Receptor 2 (HER2)-Low, Hormone Receptor Positive (HR+) Metastatic Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy (ET) (DYNASTY-Breast02) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DB-1303/BNT323, by IV, every 3 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care Chemotherapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">One of the following:</li> <li class="seamTextUnorderedListItem">Capecitabine (Cytoxan®), by mouth, daily, 2 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV, every 3 weeks</li> <li class="seamTextUnorderedListItem">Nab-paclitaxel (Abraxane®), by IV, weekly, 3 weeks on, 1 week off</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DB-1303/BNT323 is an experimental antibody-drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">DB-1303/BNT323's antibody targets HER2, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called deruxtecan.</li> <li class="seamTextUnorderedListItem">Capecitabine (Cytoxan®), paclitaxel (Taxol®), or nab-paclitaxel (Abraxane®) are chemotherapy drugs.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+ or IHC 2+/ISH-.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06018337' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.dualitybiologics.com/pipeline.html' target='_blank'>DualityBio: DB-1303 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.dualitybiologics.com/approach.html?md=1' target='_blank'>DualityBio: ADC Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li></ul>

NEAREST SITE: 318 miles City of Hope Antelope Valley Lancaster,CA

VISITS: 1 to 10 visits over 1 month

NCT ID: NCT03550391

Stereotactic Radiation or Memory Sparing Whole-Brain Radiation for Patients with 5-15 Brain Metastases

A Phase III Trial of Stereotactic Radiosurgery Compared With Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) Plus Memantine for 5-15 Brain Metastases Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Whole-brain radiation</li> <li class="seamTextUnorderedListItem">Memantine, by mouth, twice a day, for 4 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiation to metastatic brain metastases</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Radiation therapy uses high-energy x-rays to kill tumor cells that remain after surgery.</li> <li class="seamTextUnorderedListItem">Whole-brain radiation therapy (WBR) typically targets the entire brain, including the hippocampus. By avoiding the hippocampus, researchers hope to lessen the side effects of WBR.</li> <li class="seamTextUnorderedListItem">Stereotactic radiation (also called stereotactic radiosurgery) delivers focused radiation to each metastasis (met/tumor).</li> <li class="seamTextUnorderedListItem">Memantine is a medication approved for use in people with dementia, but its use in breast cancer is considered experimental.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer that have spread to the brain.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03550391' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mbcalliance.org/marina-kaplan-project' target='_blank'>The Marina Kaplan Project: Breast Cancer Brain Metastases Initiative</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.webmd.com/drugs/2/drug-77932-377/memantine-oral/memantine-oral/details' target='_blank'>Memantine</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.verywellmind.com/what-is-the-hippocampus-2795231' target='_blank'>What is the Hippocampus?</a> </li></ul>

NEAREST SITE: 336 miles Research Site Los Angeles,CA

NCT ID: NCT02264678

Ceralasertib Alone or With Chemotherapy or With Olaparib in Advanced Breast Cancer

A Modular Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD6738 in Combination With Cytotoxic Chemotherapy and/or DNA Damage Repair/Novel Anti-cancer Agents in Patients With Advanced Solid Malignancies. Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 3 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Open to all MBC patients</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ceralasertib, by mouth </li> <li class="seamTextUnorderedListItem">Carboplatin (Paraplatin®), by IV, every 3 weeks for up to 4.5 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Open to all MBC patients </i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ceralasertib, by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3: Open to Triple Negative Breast Cancer MBC patients with or without a BRCA mutation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ceralasertib, by mouth</li> <li class="seamTextUnorderedListItem">Olaparib (Lynparza®), by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">3 biopsies</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ceralasertib is a new type of targeted therapy called an ATR inhibitor. </li> <li class="seamTextUnorderedListItem">It disrupts a cancer cell's ability to repair its own DNA, which can cause the cancer cells to die. </li> <li class="seamTextUnorderedListItem">Carboplatin is a chemotherapy used to treat breast cancer. </li> <li class="seamTextUnorderedListItem">Lynparza is a PARP inhibitor approved to treat BRCA 1 or BRCA 2 positive metastatic breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02264678' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/atr-kinase-inhibitor-azd6738' target='_blank'>NCI Drug Dictionary: Ceralasertib</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/olaparib' target='_blank'>NCI Drug Dictionary: Olaparib</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.onclive.com/publications/oncology-live/2018/vol-19-no-24/targeting-cancers-achilles-heel-dna-damage-response-networks-beyond-parp' target='_blank'>OncLive: DNA Damage Response Networks Beyond PARP</a> </li></ul>

NEAREST SITE: 336 miles University of California, Los Angeles Los Angeles,CA

NCT ID: NCT03401385

DS-1062a in Advanced Triple Negative Breast Cancer

Phase 1, Two-part, Multicenter, Open-label, Multiple Dose, First-in-human Study of DS-1062a in Subjects With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DS-1062a</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DS-1062a is an investigational antibody-drug conjugate (ADC). This type of drug uses an antibody that targets cancer cells to deliver a chemotherapy directly to these cells.</li> <li class="seamTextUnorderedListItem">The antibody in this drug targets Trop2 proteins. </li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of advanced solid tumors.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03401385' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/793720' target='_blank'>NCI Drug Dictionary: DS-1062a</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/2019/05/01/mbc-news-11/' target='_blank'>Metastatic Trial Talk: Getting to the Target, Antibody Drug Conjugates in Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://tnbcfoundation.org' target='_blank'>Triple Negative Breast Cancer Foundation</a> </li></ul>

NEAREST SITE: 336 miles Ethan Lam Los Angeles,CA

VISITS: 2-3 visits

NCT ID: NCT04147494

PET/CT Scans Before Surgery for People with Stage I-IV Breast Cancer

PET Biodistribution Study of 68Ga-PSMA-11 and 68Ga-FAPI-46 in Patients With Non-prostate Cancers: an Exploratory Study With Histopathology Validation Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">68Ga-FAPi-46, by IV, 1 time</li> <li class="seamTextUnorderedListItem">PET/CT scan, 1 time</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">18F-FDG, by IV, 1 time</li> <li class="seamTextUnorderedListItem">PET/CT scan, 1 time</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">68Ga-PSMA-11, by IV, 1 time (optional)</li> <li class="seamTextUnorderedListItem">PET/CT scan, 1 time (optional)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for trial schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">68Ga-FAPi-46 and 68Ga-PSMA-11 are experimental tracers for imaging scans that may help locate cancer in the body.</li> <li class="seamTextUnorderedListItem">18F-FDG is a tracer routinely used for imaging scans that helps locate cancer in the body.</li> <li class="seamTextUnorderedListItem">A positron emission tomography (PET) scan is an imaging test that uses a radioactive substance called a tracer that can look for and attach to cancer cells.</li> <li class="seamTextUnorderedListItem">A computed tomography (CT) scan produces body pictures created by x-ray energy.</li> <li class="seamTextUnorderedListItem">The PET/CT scanner combines the PET and the CT scanners into a single device. This device combines the anatomic (body structure) information provided by the CT scan with the metabolic (body processes) information obtained from the PET scan. </li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04147494' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mskcc.org/cancer-care/patient-education/pet-ct-fdg' target='_blank'>Memorial Sloan Kettering Cancer Center: PET/CT Scans with 18F-FDG Tracer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/gallium-ga-68-fapi-46' target='_blank'>National Cancer Institute: 68Ga-FAPi-46</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mayoclinic.org/drugs-supplements/gallium-ga-68-psma-11-intravenous-route/description/drg-20506366' target='_blank'>Mayo Clinic: 68Ga-PSMA-11</a> </li></ul>

NEAREST SITE: 336 miles UCLA / Jonsson Comprehensive Cancer Center Los Angeles,CA

VISITS: 2 visits within 2 months

NCT ID: NCT04290897

Oxaloacetate to Reduce Side Effects After Treatment in People with DCIS and Stage I-III Breast Cancer

A Phase II Single Arm Trial Evaluating the Safety and Efficacy of Anhydrous Enol-Oxaloacetate on Improving Cognitive Complaints in Breast Cancer Survivors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Oxaloacetate, by mouth, daily for 2 months</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Oxaloacetate is a natural substance found in the body and is available as a nutritional supplement.</li> <li class="seamTextUnorderedListItem">Oxaloacetate may reduce inflammation in the brain that could contribute to brain problems (cognition) after cancer treatments.</li> <li class="seamTextUnorderedListItem">Cognition is your ability to think.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04290897' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/about-cancer/treatment/side-effects/memory#:~:text=Cancer%20treatments%20such%20as%20chemotherapy,during%20or%20after%20cancer%20treatment.' target='_blank'>National Cancer Institute: Memory or Concentration Problems and Cancer Treatment</a> </li></ul>

NEAREST SITE: 336 miles University of California at Los Angeles Los Angeles,CA

NCT ID: NCT04297020

Studying the Effects of Anti-Estrogen Therapy on the Brain of Women with Stage I-III Breast Cancer

Brain Health in Breast Cancer Survivors: Interaction of Menopause and Endocrine Therapy Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">1 Brain fMRI (functional MRI)</li> <li class="seamTextUnorderedListItem">Cognitive testing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">This trial will use an advanced brain MRI technique called functional MRI (fMRI).</li> <li class="seamTextUnorderedListItem">fMRI measures changes in blood flow that happen during mental activity. </li> <li class="seamTextUnorderedListItem">Research suggests that the cognitive issues experienced by some women who receive treatment for breast cancer--also called <q>chemo brain</q>--may actually be caused by anti-estrogen therapy and not chemotherapy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04297020' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.medscape.com/viewarticle/932091' target='_blank'>MedScape: In Breast Cancer, Is Chemobrain Really Endocrine Brain?</a> </li><li class='seamTextUnorderedListItem'><a href='https://en.wikipedia.org/wiki/Functional_magnetic_resonance_imaging' target='_blank'>Wikipedia: Functional MRI</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.radiologyinfo.org/en/info.cfm?pg=fmribrain' target='_blank'>RadiologyInfo.org: fMRI</a> </li></ul>

NCT ID: NCT04553770

Trastuzumab Deruxtecan Alone or With Hormone Therapy for Stage II-III HER2 Low, HR Positive Breast Cancer

A Phase II, Multicenter, Open-Label Trial to Evaluate the Safety and Efficacy of Trastuzumab Deruxtecan (DS-8201a) With or Without Anastrozole for HER2 Low Hormone Receptor Positive (HR+) Breast Cancer in the Neoadjuvant Setting Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups and recieve the following before surgery: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan-nxki (Enhertu®), by IV, every 3 weeks, over 4.5 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan-nxki (Enhertu®), by IV, every 3 weeks, over 4.5 months</li> <li class="seamTextUnorderedListItem">Anastrozole (Arimidex®), by mouth, daily, for 4.5 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">HER2 low expression is defined as IHC 1+ or IHC 2+/ISH-.</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (Enhertu®) is an antibody-drug conjugate (ADC). It uses a HER2 antibody to deliver a chemotherapy directly to cancer cells.</li> <li class="seamTextUnorderedListItem">Anastrozole (Arimidex®) is type of anti-estrogen therapy called an aromatase inhibitor. It is commonly used to treat early stage and metastatic hormone positive (ER+ and/or PR+) breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04553770' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://en.wikipedia.org/wiki/Trastuzumab_deruxtecan' target='_blank'>Wikipedia: Trastuzumab Deruxtecan</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.enhertuhcp.com/en/?utm_source=google&utm_medium=cpc&utm_campaign=branded+general_2020%3bs%3bph%3bbr%3bonc%3bhcp%3bbr&utm_content=branded+general_2020_exact&utm_term=enhertu&gclid=cj0kcqia48j9brc-arisamqu3wqel0xz_rkoi7g8nk-ckknd1pfqh_i4wknawmwg' target='_blank'>Daiichi-Sankyo Drug Information Page: Enhertu®</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/her2-low-expressing-a-new-subcategory-of-her2-negative-breast-cancer/' target='_blank'>Metastatic Trial Talk: HER2-Low Expressing, A New Subcategory of HER2 Negative Breast Cancer?</a> </li></ul>

NEAREST SITE: 336 miles UCLA Ronald Reagan Medical Center Los Angeles,CA

NCT ID: NCT05078398

Choice to Receive Opioid Pain Medication After Surgery

Postoperative Opt-In Narcotics Treatment in Breast Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Counseling about opioids before and after surgery</li> <li class="seamTextUnorderedListItem">Acetaminophen and/or ibuprofen after surgery, by mouth, 5 times</li> <li class="seamTextUnorderedListItem">Opioid after surgery (if requested)</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Hydrocodone opioid after surgery, by mouth, 5 times</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Opioids reduce pain after surgery, but they can be addictive.</li> <li class="seamTextUnorderedListItem">Hydrocodone is an opioid pain medication.</li> <li class="seamTextUnorderedListItem">Acetaminophen or ibuprofen are over the counter (OTC), non-opioid pain medication.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05078398' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/podcast/pain-after-surgery' target='_blank'>Breastcancer.org: Ways to Control Pain After Breast Surgery</a> </li></ul>

NEAREST SITE: 336 miles UCLA Los Angeles,CA

NCT ID: NCT05124912

Laser Interstitial Thermal Therapy for Brain Metastases

REMASTer: REcurrent Brain Metastases After SRS Trial Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Laser Interstitial Thermal Therapy (LITT)</li> <li class="seamTextUnorderedListItem">Stereotactic radiosurgery</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Laser Interstitial Thermal Therapy (LITT) is a minimally invasive technique to destroy brain tumors using lasers, heat, and the NeuroBlate® System (NBS).</li> <li class="seamTextUnorderedListItem">Stereotactic radiation (stereotactic radiosurgery) delivers high-dose, precisely-targeted radiation in fewer doses than traditional radiation therapy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05124912' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.monteris.com/home-page/' target='_blank'>Monteris Medical</a> </li></ul>

NEAREST SITE: 336 miles UCLA Hematology/Oncology Los Angeles,CA

VISITS: At least 1 visit per month

NCT ID: NCT05262400

PF-07220060/PF-07104091 With Hormone Therapy for Advanced HR+, HER2- Breast Cancer

A PHASE 1B/2, OPEN-LABEL, MULTICENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07220060 IN COMBINATION WITH PF-07104091 PLUS ENDOCRINE THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups based on when you enroll: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PF-07220060/PF-07104091, by mouth</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PF-07220060/PF-07104091, by mouth</li> <li class="seamTextUnorderedListItem">Letrozole (Femara®), by mouth</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PF-07220060 is an experimental targeted therapy called a CDK 4 inhibitor.</li> <li class="seamTextUnorderedListItem">PF-07104091 is an experimental targeted therapy called a CDK 2 inhibitor.</li> <li class="seamTextUnorderedListItem">CDK 2 and 4 are proteins that help cancer grow. Blocking CDK 2 and 4 helps slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">PF-07220060/PF-07104091 is a combination of PF-07220060 and PF-07104091.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a hormone therapy approved to treat postmenopausal women with breast cancer.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor degrader (SERD).</li> <li class="seamTextUnorderedListItem">Letrozole (Femara®) is a type of hormone therapy called an aromatase inhibitor. It is approved to treat hormone-positive breast cancer. </li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05262400' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://cdn.pfizer.com/pfizercom/product-pipeline/Pipeline_Update_04MAY2021.pdf?VersionId=.06Q_HtLdkBW8lme0Y3EXpraBpgGspyg' target='_blank'>Pfizer Drug Information Page: PF-07220060 and PF-07104091</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.pfizerclinicaltrials.com/find-a-trial/nct05262400-breast-cancer-trial' target='_blank'>Pfizer Trial Information Page: PF-07220060 and PF-07104091</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/femara' target='_blank'>Breastcancer.org: Letrozole (Femara®)</a> </li></ul>

NEAREST SITE: 336 miles UCLA Kaiser Permanente Center for Health Equity Los Angeles,CA

NCT ID: NCT05298605

Faith in Action: Church-Based Education and Navigation to Increase Breast Cancer Screening in Korean Women

Faith in Action! A Cluster-Randomized Trial to Evaluate the Efficacy of a Church-based Navigation Model to Increase Breast Cancer Screening Among Korean Women in Los Angeles Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Faith in Action cancer screening education and navigation curriculum</li> <li class="seamTextUnorderedListItem">American Cancer Society Screening Guidelines pamphlet</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Presentation on physical activity and nutrition</li> <li class="seamTextUnorderedListItem">American Cancer Society Screening Guidelines pamphlet</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Faith in Action is a curriculum designed to deliver cancer education and increase motivation to participate in breast cancer screening through proven approaches such as one-on-one education, small media, and workshops.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05298605' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://ucla.clinicaltrials.researcherprofiles.org/trial/NCT05298605' target='_blank'>UCLA: Faith in Action</a> </li></ul>

VISITS: 1 visit every week

NCT ID: NCT05319873

Targeted Therapy for HER2 Positive Stage II-IV Breast Cancer

A Phase 1B Trial Evaluating the Safety of Ribociclib, Tucatinib, and Trastuzumab in Patients With Metastatic, HER2+ Breast Cancer and a Multicenter, Randomized, Open-Label, Phase 2 Study of Preoperative Treatment With Ribociclib,Ttrastuzumab, Tucatinib, and Fulvestrant Versus Docetaxel, Carboplatin,Ttrastuzumab, and Pertuzumab in HR+/HER2+ Breas... Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups based on your type of cancer: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®), by mouth, daily, 3 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®), by IV, weekly</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®), by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, every 2 weeks for 1 month, then monthly</li> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®), by mouth, daily, 3 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®), by IV, weekly</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®), by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®) is a type of targeted therapy called a CDK 4/6 inhibitor. It blocks two enzymes, CDK 4 and CDK 6, that help cancer cells grow.</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®) is a type of targeted therapy called a tyrosine kinase inhibitor. It blocks an enzyme, tyrosine kinase, that helps cancer cells grow.</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®) is an anti-HER2 targeted therapy routinely used for HER2+ breast cancer.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor downregulator (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 2+.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05319873' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/kisqali' target='_blank'>Breastcancer.org: Ribociclib (Kisqali®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/herceptin' target='_blank'>Breastcancer.org: Trastuzumab (Herceptin®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/tukysa' target='_blank'>Breastcancer.org: Tucatinib (Tukysa®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li></ul>

NEAREST SITE: 336 miles University of California - Los Angeles Los Angeles,CA

NCT ID: NCT05511844

ORM-5029 Antibody Drug Conjugate for HER2 Positive or HER2 Low Breast Cancer

Phase I Multicenter, Open-Label, First-in-Human Study of ORM-5029 in Subjects With HER2-Expressing Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ORM-5029, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ORM-5029 is an experimental antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Its antibody targets HER2, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called a GSPT1 protein degrader.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05511844' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.orumrx.com/pipeline-platform' target='_blank'>Orum Therapeutics Drug Information Page: ORM-5029</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.businesswire.com/news/home/20221031005031/en/Orum-Therapeutics-Announces-First-Patient-Dosed-in-Phase-1-Clinical-Trial-of-ORM-5029-in-Development-to-Treat-HER2-Expressing-Advanced-Solid-Tumors' target='_blank'>Orum Therapeutics Press Release: ORM-5029</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li></ul>

NCT ID: NCT05585034

XmAb808 Bispecific Antibody with Immunotherapy for Advanced Triple Negative Breast Cancer

A Phase 1, First-in-Human, Dose-Finding and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of XmAb®808 in Combination With Pembrolizumab in Selected Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">XmAb808</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">XmAb808 is an experimental immunotherapy called a bispecific antibody.</li> <li class="seamTextUnorderedListItem">A bispecific antibody binds to two distinct targets and may work better than traditional antibody drugs.</li> <li class="seamTextUnorderedListItem">XmAb808 is a bispecific antibody that targets B7-H3 and CD28.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05585034' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://xencor.com/pipeline/' target='_blank'>Xencor Drug Information Page: XmAb808</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/bispecific-antibodies-for-mbc/' target='_blank'>Metastatic Trial Talk: Bispecific Antibodies: An Emerging Class Of MBC Drugs</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/immune-checkpoint-inhibitor/' target='_blank'>Metastatic Trial Talk: Update on Immunotherapy for MBC: Immune Checkpoint Inhibitors</a> </li></ul>

NCT ID: NCT05595499

Fisetin to Improve Physical Function in Older Women After Chemotherapy

A Phase II Randomized Double-Blind Placebo-Controlled Study of Fisetin to Improve Physical Function in Frail Older Breast Cancer Survivors Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fisetin, by mouth, 2 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for fisetin, by mouth, 2 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Blood tests</li> <li class="seamTextUnorderedListItem">Questionnaires</li> <li class="seamTextUnorderedListItem">Walking test</li> <li class="seamTextUnorderedListItem">Grip strength test</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fisetin is a naturally occurring substance that is found in strawberries and other foods.</li> <li class="seamTextUnorderedListItem">Fisetin eliminates cells that have stopped dividing but have not died.</li> <li class="seamTextUnorderedListItem">Chemotherapy causes a build-up of these cells which may cause inflammation. damage nearby healthy cells, and cause reduced physical function.</li> <li class="seamTextUnorderedListItem">Improving physical function is also called improving frailty.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05595499' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://restorativemedicine.org/digest/fisetin-powerful-polyphenol-supports-healthy-aging/' target='_blank'>Association for the Advancement of Restorative Medicine: Fisetin</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.urmc.rochester.edu/news/story/frailty-in-cancer-patients-young-and-old-is-linked-to-inflammation' target='_blank'>University of Rochester: Frailty and Breast Cancer</a> </li></ul>

NEAREST SITE: 336 miles University of California, Los Angeles (UCLA) Los Angeles,CA

NCT ID: NCT05877599

NT-175 TCR Immunotherapy for Advanced HLA Positive Breast Cancer with the TP53 R175H Mutation

An Open-label, Phase 1, Multicenter Study to Evaluate the Safety and Preliminary Anti-tumor Activity of NT-175 in Human Leukocyte Antigen-A*02:01-Positive Adult Subjects With Unresectable, Advanced and/or Metastatic Solid Tumors That Are Positive for the TP53 R175H Mutation Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Leukapheresis procedure</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fludarabine (Fludara®)</li> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®)</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NT-175 T cell receptor (TCR) immunotherapy, by IV</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Interleukin-2 (IL-2)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NT-175 T cell receptor (TCR) immunotherapy is an experimental immunotherapy that trains the immune system to attack cancer cells with the TP53 R175H mutation.</li> <li class="seamTextUnorderedListItem">Leukapheresis is the removal of blood by a machine to collect specific immune cells called T cells that will be modified to target cancer cells.</li> <li class="seamTextUnorderedListItem">The T cells will be grown in a lab, modified, and given back to you through an infusion.</li> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®) and fludarabine (Fludara®) are chemotherapy drugs. The main purpose of chemotherapy drugs in this trial is to make the T cells more effective in fighting cancer cells.</li> <li class="seamTextUnorderedListItem">Interleukin-2 (IL-2) may help the T cells live longer in your body.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05877599' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/adoptive-cell-therapy-2-2/' target='_blank'>Metastatic Trial Talk: Adoptive Cell Therapies: A Type of Immunotherapy for MBC</a> </li></ul>

NCT ID: NCT05978128

Increasing Breast Cancer Screening Using Advocates and Supporters

Utilizing Spheres of Influence to Increase Cancer Screening: Empowering Community Health Advocates Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Access to online educational materials, 3 times within 2 years</li> <li class="seamTextUnorderedListItem">Meet with a patient navigator</li> <li class="seamTextUnorderedListItem">Education materials to share with friends/family on benefits of breast cancer screening</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Breast cancer screening with mammography is widely accepted and commonly used.</li> <li class="seamTextUnorderedListItem">Advocates and supporters of lung cancer screening may increase the willingness to receive this screening.</li> <li class="seamTextUnorderedListItem">This trial also includes lung cancer screening.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05978128' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 337 miles Disney Family Cancer Center Burbank,CA

NCT ID: NCT05894239

Inavolisib and Phesgo for Advanced HER2 Positive Breast Cancer with a PIK3CA Mutation

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo As Maintenance Therapy After First Line Induction Therapy in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer... Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Phesgo, by injection, every 3 weeks</li> <li class="seamTextUnorderedListItem">Chemotherapy</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Inavolisib, by mouth, daily</li> <li class="seamTextUnorderedListItem">Phesgo, by injection, every 3 weeks</li> <li class="seamTextUnorderedListItem">Standard of care hormone therapy (optional, if relevant)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Control</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Phesgo, by injection, every 3 weeks</li> <li class="seamTextUnorderedListItem">Chemotherapy</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for inavolisib, by mouth, daily</li> <li class="seamTextUnorderedListItem">Phesgo, by injection, every 3 weeks</li> <li class="seamTextUnorderedListItem">Standard of care hormone therapy (optional, if relevant)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">You will first receive induction therapy (initial therapy used when treating a disease) with Phesgo and chemotherapy.</li> <li class="seamTextUnorderedListItem">Inavolisib is an experimental targeted therapy called a PI3K inhibitor. Blocking the PI3K pathway may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Phesgo is a combination of two anti-HER2 targeted therapies: Perjeta® (pertuzumab) and Herceptin® (trastuzumab). It also includes a protein called hyaluronidase which helps your body absorb the targeted therapies.</li> <li class="seamTextUnorderedListItem">Pertuzumab and trastuzumab are typically given by IV. With Phesgo, you can receive these therapies by injection, which shortens the length of time it takes to receive treatment.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05894239' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.gene.com/medical-professionals/pipeline/inavolisib-gdc-0077' target='_blank'>Genentech: Inavolisib Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted_therapies/phesgo' target='_blank'>Breastcancer.org: Phesgo</a> </li></ul>

NEAREST SITE: 338 miles Sarcoma Oncology Santa Monica,CA

NCT ID: NCT05827614

BBI-355 Targeted Therapy for Advanced Breast Cancer With Oncogene Amplifications

An Open-Label, First-in-Human, Dose-Escalation and Dose-Expansion, Phase 1/2 Study of BBI-355 and BBI-355 in Combination With Select Therapies in Subjects With Locally Advanced or Metastatic Solid Tumors With Oncogene Amplifications Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BBI-355, by mouth, every other day</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BBI-355 is an inhibitor of checkpoint kinase 1 (CHK1). Inhibiting CHK1 may kill cancer cells with a feature called <q>oncogene amplification</q> by blocking their ability to grow.</li> <li class="seamTextUnorderedListItem">Oncogene amplification is a type of cancer-causing DNA abnormality. Estrogen may be responsible for some oncogene amplifications.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05827614' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://boundlessbio.com/what-we-do/' target='_blank'>Boundless Bio: BBI-355</a> </li><li class='seamTextUnorderedListItem'><a href='https://hms.harvard.edu/news/how-breast-cancer-arises' target='_blank'>Harvard Medical School: What is Oncogene Amplification?</a> </li></ul>

NEAREST SITE: 338 miles Sarcoma Oncology Center Santa Monica,CA

NCT ID: NCT06471673

BRIA-OTS Cell Therapy for Metastatic Breast Cancer

A Study of BRIA-OTS Cellular Immunotherapy in Metastatic Recurrent Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following as part of the Bria-OTS regimen: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®), 2-3 days before BC1 cells</li> </ul> <p class="seamTextPara"> followed 2-3 days later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BC1 cells, by injection, every 3 weeks</li> <li class="seamTextUnorderedListItem">Peginterferon, every 3 weeks</li> <li class="seamTextUnorderedListItem">Tislelizumab (Tevimbra®), every 3 weeks</li> <li class="seamTextUnorderedListItem">Imaging scans, every 1-3 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The Bria-OTS regimen is an experimental cell therapy with BC1 cells.</li> <li class="seamTextUnorderedListItem">Before you receive the cell therapy, you will receive cyclophosphamide (Cytoxan®) chemotherapy to prepare your body to receive the cells.</li> <li class="seamTextUnorderedListItem">Tislelizumab (Tevimbra®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">Tislelizumab (Tevimbra®) is approved to treat other cancers. Its use in this trial is considered experimental.</li> <li class="seamTextUnorderedListItem">Peginterferon is an immunotherapy used to regulate your immune response to the cell therapy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06471673' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 339 miles John Wayne Cancer Institute, Providence Saint John's Health Center Santa Monica,CA

VISITS: 1 visit that coincides with surgery

NCT ID: NCT04603209

A Registry and IORT Radiation Therapy During Lumpectomy for DCIS and Stage I-III Breast Cancer

Research Registry for Intra-Operative Radiotherapy (IORT) During Breast Conserving Surgery in Patients With in Situ and Early Stage Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">IORT (Intraoperative radiation therapy), one time during lumpectomy (breast conserving surgery)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">A lumpectomy is sometimes called a partial mastectomy. </li> <li class="seamTextUnorderedListItem">Typically, a lumpectomy (breast conserving surgery) is followed by 4 to 6 weeks of daily radiation therapy.</li> <li class="seamTextUnorderedListItem">In this trial, you will receive intraoperative radiation therapy (IORT) one time during your lumpectomy. </li> <li class="seamTextUnorderedListItem">IORT delivers a high dose of radiation during surgery to the area in the breast where the tumor was removed. This means you only receive one dose, and it may cause less damage to the healthy tissue around the tumor. </li> <li class="seamTextUnorderedListItem">This trial will also create a data registry of people receiving IORT so that researchers can study the long-term safety and anti-cancer activity of this type of radiation therapy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04603209' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/research-news/20131203' target='_blank'>Breastcancer.org: Studies Show Risks and Benefits of Intraoperative Radiation Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cdc.gov/cancer/npcr/value/registries.htm' target='_blank'>CDC: How Cancer Registries Work</a> </li></ul>

NEAREST SITE: 339 miles Providence St. Johns Health Center Santa Monica,CA

VISITS: 1-2 visits every month

NCT ID: NCT04851613

Afuresertib Targeted Therapy with Fulvestrant for Advanced HR+, HER2- Breast Cancer with PIK3CA, AKT1, or PTEN Mutations

A Phase Ib/III Study to Evaluate the Efficacy and Safety of Afuresertib Plus Fulvestrant in Patients With Locally Advanced or Metastatic HR+/HER2- Breast Cancer Who Failed Standard of Care Therapies (LAE205INT3101) Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Afuresertib (LAE002), by mouth, daily</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, every 2 weeks for 1 month, then monthly</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Fulvestrant and Placebo</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for afuresertib (LAE002), by mouth, daily</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, every 2 weeks for 1 month, then monthly</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Afuresertib (LAE002) is an experimental targeted therapy called an AKT inhibitor. It may slow or stop cancer cells from growing by blocking the enzyme (protein) AKT.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor downregulator (SERD). SERDs bind to and break down estrogen receptors.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04851613' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.saintjohnscancer.org/clinical-trials/clinical-trial/study-evaluating-efficacy-safety-of-afuresertib-plus-fulvestrant-in-patients-w-locally-advanced-or-metastatic-hr-her2-breast-cancer/' target='_blank'>Saint John’s Cancer Institute: Clinical Trial Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.prnewswire.com/news-releases/laekna-therapeutics-receives-ind-approvals-in-china-and-us-for-phase-ibiii-global-multi-center-clinical-study-of-afuresertib-in-combination-with-fulvestrant-for-patients-with-hrher2--breast-cancer-301364146.html' target='_blank'>Laekna Therapeutics Press Release: Afuresertib With Fulvestrant for Advanced HR+, HER2- Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li></ul>

NEAREST SITE: 339 miles University of California, Los Angeles Santa Monica,CA

VISITS: 2 visits per month

NCT ID: NCT04890613

CX-5461 for Advanced Breast Cancer with a BRCA2 or PALB2 Mutation

Phase Ib Expansion Study of CX-5461 in Patients With Solid Tumours and BRCA2 and/or PALB2 Mutation Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CX-5461, by IV, 2 times per month</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CX-5461 is an experimental targeted therapy. </li> <li class="seamTextUnorderedListItem">It targets cells with a Homologous Recombination Deficiency (HRD) mutation. </li> <li class="seamTextUnorderedListItem">It works by slowing down the growth of cancer cells or causing cancer cells to die.</li> <li class="seamTextUnorderedListItem">This trial also is enrolling patients with other types of advanced cancers.</li> <li class="seamTextUnorderedListItem">Targets or mutations: BRCA2, PALB2</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04890613' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.prnewswire.com/news-releases/senhwa-biosciences-receives-us-fda-study-may-proceed-letter-to-treat-brca2-or-palb2-solid-tumors-with-cx-5461-301198347.html' target='_blank'>Senhwa Biosciences Press Release: CX-5461</a> </li></ul>

NEAREST SITE: 339 miles UCLA Department of Medicine Hematology Oncology Los Angeles,CA

NCT ID: NCT05180474

GEN1047 for Stage III or Stage IV Breast Cancer

First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1047 in Subjects With Malignant Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">GEN1047, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule.</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">GEN1047 is a bispecific antibody that helps T cells kill cancer cells.</li> <li class="seamTextUnorderedListItem">A bispecific antibody binds to two distinct targets and may work better than traditional antibody drugs.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05180474' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.genmab.com/pipeline/' target='_blank'>Genmab: GEN1047</a> </li></ul>

NEAREST SITE: 339 miles NGM Clinical Study Site Los Angeles,CA

NCT ID: NCT05215574

NGM831 with Pembrolizumab for Advanced Breast Cancer

A Phase 1/1b Dose Escalation/Expansion Study of NGM831 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NGM831, by IV, every 3 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NGM831, by IV, every 3 weeks</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NGM831 is an experimental immunotherapy called an ILT3 inhibitor.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor.</li> <li class="seamTextUnorderedListItem">Blocking ILT3 and PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This study is also enrolling patients with other types of solid tumors.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05215574' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://ir.ngmbio.com/news-releases/news-release-details/ngm-bio-discloses-fourth-oncology-development-candidate-ngm831' target='_blank'>NGM Bio Press Release: NGM831</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li></ul>

VISITS: Hospital stay may be required

NCT ID: NCT05274451

LYL797 CAR T-Cell Immunotherapy for Triple Negative, ROR1 Positive Advanced Breast Cancer

A Phase 1 Study to Assess the Safety and Efficacy of LYL797, ROR1-Targeting CAR T Cells, in Adults With Relapsed and/or Refractory Solid-Tumor Malignancies Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LYL797 CAR T-cell therapy</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Requires 1 biopsy</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule. Hospital stay may be required.</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LYL797 is an experimental type of immunotherapy called CAR T-cell/CAR-T therapy.</li> <li class="seamTextUnorderedListItem">CAR-T or CAR T cell therapy is a personalized immunotherapy made from your white blood cells.</li> <li class="seamTextUnorderedListItem">The cells are removed from your blood, modified with chimeric antigen receptors (CARs) that allow them to attack proteins on cancer cells, and then put back in your body.</li> <li class="seamTextUnorderedListItem">The CAR T-cell therapy being used in this study trains the immune system to attack ROR1 positive cancer cells</li> <li class="seamTextUnorderedListItem">This study is also enrolling patients with other types of ROR1 positive cancers.</li> <li class="seamTextUnorderedListItem">Targets or mutations: ROR1</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05274451' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://lyell.com/our-pipeline' target='_blank'>Lyell Immunopharma Drug Information Page: LYL797</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.dana-farber.org/cellular-therapies-program/car-t-cell-therapy/faq-about-car-t-cell-therapy/' target='_blank'>Dana-Farber Cancer Institute: CAR T-Cell Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy#section-adoptive-cell-therapy' target='_blank'>Breastcancer.org: CAR T-Cell Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/from-the-experts/what-is-car-t-therapy/' target='_blank'>Metastatic Trial Talk: What is CAR-T Therapy?</a> </li></ul>

NEAREST SITE: 339 miles Providence Saint John's Hospital Santa Monica,CA

NCT ID: NCT05289466

Intraoperative Radiotherapy During Partial Mastectomy for Women Ages 50+ with Recurrent DCIS or Stage I-III Breast Cancer

Oncoplastic Partial Mastectomy With Intraoperative Radiation Therapy (IORT) in Early Stage Breast Cancer Patients With Prior History of Chest Wall Radiation Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Intraoperative radiotherapy (IORT), 1 time</li> <li class="seamTextUnorderedListItem">Partial mastectomy</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Intraoperative radiotherapy (IORT) is radiation given at the time of a partial mastectomy.</li> <li class="seamTextUnorderedListItem">Radiation therapy uses high-energy x-rays to damage cancer cell DNA. These x-rays stop cancer cells from dividing and growing, thus slowing or stopping tumor growth.</li> <li class="seamTextUnorderedListItem">A partial mastectomy is surgery to remove part of the breast and is sometimes called a lumpectomy.</li> <li class="seamTextUnorderedListItem">Node negative means cancer has not spread to your lymph nodes.</li> <li class="seamTextUnorderedListItem">Neoadjuvant therapy is when you receive treatment before surgery. Doctors use it to shrink tumors and to see how your cancer responds to the given therapies.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with lobular breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05289466' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/radiation-therapy/intraoperative' target='_blank'>Breastcancer.org: Intraoperative Radiation Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/surgery/breast-reconstruction/types/oncoplastic-lumpectomy' target='_blank'>Breastcancer.org: Partial Mastectomy</a> </li></ul>

NEAREST SITE: 339 miles UCLA Santa Monica,CA

NCT ID: NCT05377996

XMT-1660 Antibody Drug Conjugate for Advanced Breast Cancer

A Phase 1, First-in-human, Dose Escalation and Expansion, Multicenter Study of XMT-1660 in Participants With Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">XMT-1660, by IV</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">XMT-1660 is an experimental antibody-drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">XMT-1660's antibody targets B7-H4, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called dolasynthen.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05377996' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 339 miles UCLA Health (Santa Monica Cancer Care) Santa Monica,CA

NCT ID: NCT05708950

KVA12123 Immunotherapy for Advanced Breast Cancer

A Phase 1/2 Open-label Trial of KVA12123 Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">KVA12123, by IV, every 2 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">KVA12123, by IV, every 2 weeks</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), every 1.5 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Imaging scans, every 1.5 months</li> <li class="seamTextUnorderedListItem">Physical exams</li> <li class="seamTextUnorderedListItem">Heart function tests</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">KVA12123 is an experimental immunotherapy that binds to VISTA to stimulate the immune system to go after and kill cancer cells.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05708950' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://kinetabio.com/kva12123/' target='_blank'>Kineta: KVA12123 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li></ul>

NEAREST SITE: 339 miles Saint John's Cancer Institute Santa Monica,CA

NCT ID: NCT05710328

DIRECT: PET/CT Scan to Predict Response to Chemotherapy Before Surgery for Stage II-III HER2 Positive Breast Cancer

Interim FDG-PET/CT for PreDIcting REsponse of HER2+ Breast Cancer to Neoadjuvant Therapy: DIRECT Trial Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PET/CT scan with FDG, by IV, 2 times</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">FDG is a radioactive tracer that is given in a vein before PET/CT scans to help identify areas of active cancer.</li> <li class="seamTextUnorderedListItem">PET and and CT scans are imaging techniques that make detailed, computerized pictures of areas inside the body.</li> <li class="seamTextUnorderedListItem">A positron emission tomography (PET) scan is an imaging test that uses a radioactive substance called a tracer that can look for and attach to cancer cells.</li> <li class="seamTextUnorderedListItem">A computed tomography (CT) scan produces body pictures created by x-ray energy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05710328' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://ecog-acrin.org/clinical-trials/ea1211-direct-breast-cancer/' target='_blank'>ECOG-ACRIN Cancer Research Group: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/research-news/certain-pet-scan-detects-recurrence-better' target='_blank'>Breastcancer.org: FDG PET/CT Scan</a> </li></ul>

NEAREST SITE: 339 miles UCLA Hematology/Oncology - Santa Monica Santa Monica,CA

NCT ID: NCT05785741

DB-1310 Antibody Drug Conjugate for Advanced Breast Cancer

A Phase 1/2a, Multicenter, Open-Label, Non-Randomized First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1310 in Subjects With Advanced/Metastatic Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DB-1310, by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DB-1310 is an experimental targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">DB-1310's antibody targets HER3, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05785741' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.dualitybiologics.com/approach.html?md=1' target='_blank'>DualityBio: ADC Information Page</a> </li></ul>

NEAREST SITE: 339 miles UCLA Hematology/Oncology Santa Monica,CA

NCT ID: NCT05887492

TNG260 Targeted Therapy with Immunotherapy for Advanced Breast Cancer with STK11 Mutations

A Phase 1/2, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of TNG260 as Single Agent and in Combination With an Anti-PD-1 Antibody In Patients With STK11 Mutated Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">TNG260, by mouth</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">TNG260 is an experimental targeted therapy called a CoREST inhibitor. CoREST inhibitors may activate the immune system to go after and kill cancer cells.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">Targets or mutations: STK11</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05887492' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.tangotx.com/pipeline/' target='_blank'>Tango Therapeutics: TNG260 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.tangotx.com/programs/corest/' target='_blank'>Tango Therapeutics: CoREST Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li></ul>

NEAREST SITE: 339 miles The Angeles Clinic and Research Institute - West Los Angeles Office Los Angeles,CA

NCT ID: NCT05888831

BMS-986449 With or Without Nivolumab for Advanced Breast Cancer

A Phase 1/2 Study of BMS-986449 Alone and in Combination With Nivolumab in Participants With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BMS-986449</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BMS-986449</li> <li class="seamTextUnorderedListItem">Nivolumab (Opdivo®), by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BMS-986449 is an experimental cancer drug.</li> <li class="seamTextUnorderedListItem">Nivolumab (Opdivo®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05888831' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.bmsstudyconnect.com/no/en/clinical-trials/NCT05888831.html' target='_blank'>Bristol-Myers Squib: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a614056.html' target='_blank'>MedLine Plus: Nivolumab (Opdivo®)</a> </li></ul>

NEAREST SITE: 340 miles Valkyrie Clinical Trials Los Angeles,CA

NCT ID: NCT06244485

Valemetostat Tosylate Targeted Therapy with ADC for Advanced HER2 Low Breast Cancer

A Phase 1b, Multicenter, Open-Label Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Valemetostat tosylate, by mouth, daily</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (T-DXd, Enhertu®), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Valemetostat tosylate is an experimental targeted therapy called a EZH1/2 inhibitor. Blocking EZH1/2 may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (T-DXd, Enhertu®) is an antibody drug conjugate (ADCs).</li> <li class="seamTextUnorderedListItem">An antibody drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (T-DXd, Enhertu®)'s antibody targets HER2 and delivers an anti-cancer drug called deruxtecan.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+ or IHC 2+/ISH-.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06244485' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.daiichisankyo.com/rd/pipeline/' target='_blank'>Daiichi Sankyo: Valemetostat Tosylate Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy' target='_blank'>Breastcancer.org: Targeted Therapy</a> </li></ul>

NCT ID: NCT06324357

Zongertinib Targeted Therapy with ADC for Advanced HER2+ Breast Cancer

Beamion BCGC-1: A Phase Ib Dose Escalation and Phase II Dose Optimization, Randomized, Open-label, Multicenter Trial of Oral Zongertinib (BI 1810631) in Combination With Intravenous Trastuzumab Deruxtecan (T-DXd) or in Combination With Intravenous Trastuzumab Emtansine (T-DM1) for Treatment of Patients With Advanced HER2+ Metastatic Breast Cance... Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Zongertinib (BI 1810631), by mouth</li> <li class="seamTextUnorderedListItem">Trastuzumab emtansine (T-DM1, Kadcyla®), by IV</li> <li class="seamTextUnorderedListItem">CT scans</li> <li class="seamTextUnorderedListItem">MRI scans</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Zongertinib (BI 1810631), by mouth</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (T-DXd, Enhertu®), by IV</li> <li class="seamTextUnorderedListItem">CT scans</li> <li class="seamTextUnorderedListItem">MRI scans</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Zongertinib is an experimental anti-HER2 targeted therapy called a tyrosine kinase inhibitor. It blocks an enzyme, tyrosine kinase, that helps cancer cells grow.</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (T-DXd, Enhertu®) and trastuzumab emtansine (T-DM1, Kadcyla®) are antibody drug conjugates (ADCs).</li> <li class="seamTextUnorderedListItem">An antibody drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (T-DXd, Enhertu®)'s antibody targets HER2 and delivers an anti-cancer drug called deruxtecan.</li> <li class="seamTextUnorderedListItem">Trastuzumab emtansine (T-DM1, Kadcyla®)'s antibody targets HER2 and delivers an anti-cancer drug called DM1.</li> <li class="seamTextUnorderedListItem">A computed tomography (CT) scan produces body pictures created by x-ray energy.</li> <li class="seamTextUnorderedListItem">A magnetic resonance imaging (MRI) scan produces body pictures created by using magnetic energy rather than x-ray energy.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06324357' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/?_gl=1*msj5sm*_ga*NDI3ODYxOTY5LjE2NzE2MzcwODA.*_ga_Y9F235S3X2*MTcxMDc3NDgwNy40MTEuMS4xNzEwNzc2MTM5LjQ2LjAuMA..' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.boehringer-ingelheim.com/science/human-pharma/clinical-pipeline/oncology/zongertinib-her2-tyrosine-kinase-inhibitor-tki' target='_blank'>Boehringer Ingelheim: Zongertinib (BI 1810631) Drug Information Page</a> </li></ul>

NEAREST SITE: 341 miles Cedars-Sinai Medical Center Los Angeles,CA

VISITS: 1 visit every 3 weeks, ongoing

NCT ID: NCT03025035

Keytruda for Advanced BRCA+ Breast Cancer

Open Label, Phase II Pilot Study of Immune Checkpoint Inhibition With Pembrolizumab in Advanced BRCA-mutated Breast Cancers Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a checkpoint inhibitor. It gets the immune system to go after cancer cells by blocking the protein PD-1.</li> <li class="seamTextUnorderedListItem">Keytruda is approved to treat certain types of cancers, including breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03025035' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet' target='_blank'>NCI: BRCA1 and BRCA2</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.keytruda.com' target='_blank'>Merck Oncology Information Page: Keytruda</a> </li></ul>

VISITS: 3 visits every month, ongoing

NCT ID: NCT03129139

Minnelide™ Capsules and Chemotherapy for Metastatic Breast Cancer

A Phase 1, Multi-Center, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Minnelide™ Capsules Given Alone or in Combination With Protein-Bound Paclitaxel in Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Minnelide™, by mouth, daily (3 weeks on, 1 week off), ongoing</li> <li class="seamTextUnorderedListItem">Abraxane® (protein-bound paclitaxel), by IV, once a week (3 weeks on, 1 week off), ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Minnelide™ is an experimental heat shock protein (HSP) inhibitor. </li> <li class="seamTextUnorderedListItem">Abraxane is used to treat metastatic breast cancer. </li> <li class="seamTextUnorderedListItem">This study is also enrolling people with other types of cancers.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03129139' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-terms/def/protein-bound-paclitaxel' target='_blank'>NCI Dictionary of Cancer Terms: Protein-bound Paclitaxel</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/triptolide-analogue' target='_blank'>NCI Drug Dictionary: Triptolide Analogue (Minnelide™)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515388/' target='_blank'>Journal Article: Minnelide™ for Pancreatic and Liver Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.abraxane.com/mbc/' target='_blank'>Drug Company Information Page: Abraxane</a> </li></ul>

NEAREST SITE: 341 miles Cedars Sinai Medical Center Los Angeles,CA

VISITS: Number of visits unavailable, over 2 months

NCT ID: NCT03546686

Immunotherapy & Cryoablation Before Surgery in Taxane Treated Triple Negative or ER Low, HER2- Tumors

A Randomized Phase 2 Study of Peri-Operative Ipilimumab, Nivolumab and Cryoablation Versus Standard Peri-Operative Care in Women With Hormone Receptor-Negative, HER2-Negative Early Stage/Resectable Breast Cancer. Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ipilimumab (Yervoy®), by IV, 1-5 days prior to core biopsy and cryoablation</li> <li class="seamTextUnorderedListItem">Nivolumab (Opdivo®), by IV, 1-5 days prior to core biopsy and cryoablation, and then every 2 weeks after surgery, for 6 weeks</li> <li class="seamTextUnorderedListItem">Core biopsy/Cryoablation, 7-10 days prior to surgery</li> <li class="seamTextUnorderedListItem">Breast surgery (standard-of-care) </li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Breast surgery</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cryoablation uses extreme cold to kill cancer cells. It is not an established breast cancer treatment. </li> <li class="seamTextUnorderedListItem">Yervoy is an immunotherapy. It gets the immune system to see cancer cells by blocking the CTLA-4 protein. It is approved to treat metastatic melanoma. Its use in breast cancer is considered experimental. </li> <li class="seamTextUnorderedListItem">Opdivo is an immunotherapy that gets the immune system to go after cancer cells by blocking a protein called PD-1. It is approved to treat certain types of cancer. Its use in breast cancer is considered experimental.</li> <li class="seamTextUnorderedListItem">Breast cancer that tests positive for 1%-10% estrogen receptors is called ER Low.</li> <li class="seamTextUnorderedListItem">This trial is enrolling women with triple negative as well as ER Low breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03546686' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/ipilimumab-yervoy' target='_blank'>Cancer Research UK: Ipilimumab (Yervoy)</a> </li><li class='seamTextUnorderedListItem'><a href='http://chemocare.com/chemotherapy/drug-info/Nivolumab.aspx' target='_blank'>Chemocare: Nivolumab</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/surgery/cryotherapy' target='_blank'>Breastcancer.org: Cryotherapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.sciencedaily.com/releases/2018/11/181128082721.htm' target='_blank'>Science Daily: Cryoablation</a> </li></ul>

NCT ID: NCT04365374

Gamma Tile Surgically Targeted Radiation Therapy after Brain Surgery for Brain Metastasis

A Phase 3 Randomized Controlled Trial of Post-Surgical Stereotactic Radiotherapy (SRT) Versus Surgically Targeted Radiation Therapy (STaRT) With Gamma Tile for Treatment of Newly Diagnosed Metastatic Brain Tumors. Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Brain surgery to remove tumor and implant Gamma Tile device</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Gamma Tile Surgically Targeted Radiation Therapy (STaRT)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Brain surgery to remove tumor</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiation</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cognitive testing</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Gamma Tile Surgically Targeted Radiation Therapy (STaRT) is a FDA-cleared radiation therapy.</li> <li class="seamTextUnorderedListItem">Gamma Tile is a device implanted during surgery that delivers radiation directly to the tumor, called Surgically Targeted Radiation Therapy (STaRT).</li> <li class="seamTextUnorderedListItem">Stereotactic radiation (stereotactic radiosurgery) delivers high-dose, precisely-targeted radiation in fewer doses than traditional radiation therapy.</li> <li class="seamTextUnorderedListItem">Additional brain tumors not removed during surgery will be treated with stereotactic radiation alone, which is standard of care.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04365374' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li></ul>

VISITS: 1 visit every 6 months (coincides with standard follow up visits), for up to 7 years

NCT ID: NCT04567420

A ctDNA Blood Test to Screen for Recurrence for Stage II-III ER+, HER2- Breast Cancer

A Randomized Phase II Trial Of Circulating Tumor DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ctDNA blood test, every 4 to 6 months, for up to 7 years</li> </ul> <p class="seamTextPara"> If a ctDNA blood test is positive, you will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), by mouth, daily (3 weeks on, 1 week off), ongoing</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, monthly, ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Your current anti-hormone therapy (an aromatase inhibitor or tamoxifen)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Circulating tumor DNA (ctDNA) are small bits of cancer cell DNA that specific tests can find in the bloodstream. </li> <li class="seamTextUnorderedListItem">Researchers are studying if a test looking for ctDNA in the bloodstream can determine if there will be a recurrence (coming back) of a person's breast cancer. </li> <li class="seamTextUnorderedListItem">The ctDNA blood test used in this trial is called Signatera. </li> <li class="seamTextUnorderedListItem">This trial is also studying if a recurrence can be stopped or delayed by giving people with a positive ctDNA test additional treatment.</li> <li class="seamTextUnorderedListItem">The additional treatment in this trial includes Palbociclib (Ibrance®) and Fulvestrant (Faslodex®).</li> <li class="seamTextUnorderedListItem">Palbociclib is commonly used with anti-estrogen therapy for metastatic, hormone-positive (ER+ and/or PR+), HER2-negative (HER2-) breast cancer, but its use in this trial is considered experimental.</li> <li class="seamTextUnorderedListItem">Fulvestrant is a type of anti-estrogen therapy called a SERD (selective estrogen receptor degrader). It is approved to treat some people with advanced HR+ breast cancer.</li> <li class="seamTextUnorderedListItem">For this trial, some of the definitions of cancer at high risk of recurrence include: </li> <li class="seamTextUnorderedListItem">Cancer found in 4 or more lymph nodes, or </li> <li class="seamTextUnorderedListItem">A tumor 5 cm or larger, or</li> <li class="seamTextUnorderedListItem">Cancer found in 1 to 3 lymph nodes, and your tumor was at least 3 cm, or grade 3 or, your Oncotype DX score was greater than 26, MammaPrint score was high risk, EndoPredict was greater than 4, or Prosigna score was greater than 60.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04567420' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/genetics/understanding/testing/circulatingtumordna/' target='_blank'>What is Circulating Tumor DNA and How is it Used to Diagnose and Manage Cancer?</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.natera.com/oncology/signatera-advanced-cancer-detection/' target='_blank'>Natera ctDNA Test Information Page: Signature</a> </li><li class='seamTextUnorderedListItem'><a href='https://ascopost.com/issues/january-25-2021/a-tale-of-two-cdk46-inhibitors-in-early-breast-cancer/' target='_blank'>The ASCO Post: A Tale of Two CDK4/6 Inhibitors in Early Breast Cancer</a> </li></ul>

NEAREST SITE: 341 miles Cedars-Sinai Medical Center West Hollywood,CA

NCT ID: NCT04722341

Time-Restricted Eating to Reduce Treatment Side Effects for People with Stage II-III Breast Cancer

Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Time-restricted eating (TRE) schedule, 8 hour daily eating period, 6 months</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Control</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Regular eating schedule, 6 months</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fasting may protect healthy cells from chemotherapy and radiation side effects.</li> <li class="seamTextUnorderedListItem">Time-restricted eating (TRE) involves eating within a period of 10 hours or less, followed by fasting for at least 14 hours daily.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04722341' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/research-news/can-fasting-reduce-recurrence-risk' target='_blank'>Breastcancer.org: Can Fasting 13 Hours or More at Night Reduce Recurrence Risk?</a> </li></ul>

NEAREST SITE: 341 miles Ellison Institute of Technology Los Angeles,CA

NCT ID: NCT05252390

NUV-868 Targeted Therapy for Advanced Triple Negative Breast Cancer

Phase 1/2 Safety and Efficacy Study of NUV-868 as Monotherapy and in Combination With Olaparib or Enzalutamide in Adult Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 3 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NUV-868, by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NUV-868, by mouth, daily</li> <li class="seamTextUnorderedListItem">Olaparib (Lynparza®), by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NUV-868, by mouth, daily</li> <li class="seamTextUnorderedListItem">Enzalutamide (Xtandi®), by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NUV-868 is an experimental targeted therapy called a BET inhibitor. Blocking BET may help slow or stop the growth of cancer cells.</li> <li class="seamTextUnorderedListItem">Olaparib (Lynparza®) is a type of targeted therapy called a PARP inhibitor. PARP inhibitors work by blocking the action of poly (ADP-ribose) polymerase, an enzyme that helps repair DNA.</li> <li class="seamTextUnorderedListItem">Enzalutamide (Xtandi®) is a type of targeted therapy called an androgen receptor (AR) inhibitor. It is approved to treat advanced prostate cancer.</li> <li class="seamTextUnorderedListItem">This trial is enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: BRCA1, BRCA2</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05252390' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.nuvationbio.com/pipeline/' target='_blank'>Nuvation Bio: NUV-868 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/lynparza' target='_blank'>Breastcancer.org: Olaparib (Lynparza®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a612033.html' target='_blank'>MedlinePlus: Enzalutamide (Xtandi®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://tnbcfoundation.org/' target='_blank'>Triple Negative Breast Cancer Foundation</a> </li></ul>

NCT ID: NCT05318469

Ivermectin and Balstilimab Immunotherapy for Metastatic Triple Negative Breast Cancer

A Phase I/II Study Evaluating the Safety and Efficacy of Ivermectin in Combination With Balstilimab in Patients With Metastatic Triple Negative Breast Cancer With Expansion Cohort in PD-L1 Negative TNBC Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ivermectin (Stromectol®), by mouth, 3 days every week</li> <li class="seamTextUnorderedListItem">Balstilimab, by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ivermectin (Stromectol®) is an anti-parasite medicine that may also help block the formation of growths that may become cancer. In this trial, ivermectin (Stromectol®) is considered experimental.</li> <li class="seamTextUnorderedListItem">Bastilimab is an experimental immunotherapy called a CTLA-4 inhibitor, which is a type of immune checkpoint inhibitor. Blocking CTLA-4 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">Giving ivermectin with balstilimab may increase the ability of balstilimab to shrink tumors in people with triple negative breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05318469' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cityofhope.org/breakthroughs/drug-combo-shows-promise-against-triple-negative-breast-cancer' target='_blank'>City of Hope: The Effect of Ivermectin and Bastilimab Together on Enhancing the Immune System's Ability to Kill Cancer Cells</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/immune-checkpoint-inhibitor/?utm_medium=email&utm_source=subscribers&utm_campaign=Oct2023&utm_content=Email102023' target='_blank'>Metastatic Trial Talk: Update on Immunotherapy for MBC: Immune Checkpoint Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://my.clevelandclinic.org/health/drugs/20954-ivermectin-tablets' target='_blank'>Cleveland Clinic: Ivermectin (Stromectol®)</a> </li></ul>

VISITS: 10 visits within 2 months

NCT ID: NCT05491226

Immunotherapy, Targeted Therapy, and Radiation Therapy for Women with Stage I-III Triple Negative Breast Cancer

IIT2021-01-Shiao-CSF1Ri: Reinvigorating TNBC Response to Immunotherapy With Combination Myeloid Inhibition and Radiation Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks for 1.5 months</li> <li class="seamTextUnorderedListItem">Radiation therapy, daily for 3 days</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Axatilimab, by IV, weekly for 1 month</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">Axatilimab is an experimental targeted therapy called a CSF-1R inhibitor. Blocking CSR-1R may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Radiation therapy uses high-energy x-rays to damage cancer cell DNA. These x-rays stop cancer cells from dividing and growing, thus slowing or stopping tumor growth.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+ and ISH-.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05491226' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://syndax.com/pipeline/axatilimab/' target='_blank'>Syndax: Axatilimab Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/radiation-therapy' target='_blank'>Breastcancer.org: Radiation Therapy</a> </li></ul>

NCT ID: NCT05941507

LCB84 Antibody Drug Conjugate With and Without Immunotherapy for Advanced Breast Cancer

A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of TROP2-Directed Antibody-Drug Conjugate LCB84, as a Single Agent and in Combination With an Anti-PD-1 Ab, in Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LCB84, by IV, every 3 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LCB84, by IV, every 3 weeks</li> <li class="seamTextUnorderedListItem">PD-1 inhibitor, by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LCB84 is an experimental targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">LCB84's antibody targets TROP2, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called MMAE.</li> <li class="seamTextUnorderedListItem">PD-1 inhibitors are a type of immunotherapy called immune checkpoint inhibitors. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05941507' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/immune-checkpoint-inhibitor/?utm_medium=email&utm_source=subscribers&utm_campaign=Oct2023&utm_content=Email102023' target='_blank'>Metastatic Trial Talk: Update on Immunotherapy for MBC: Immune Checkpoint Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors' target='_blank'>National Cancer Institute: Immune Checkpoint Inhibitors</a> </li></ul>

NEAREST SITE: 342 miles California Research Institute Los Angeles,CA

NCT ID: NCT05150691

DB-1303 for Advanced HER2 Positive or HER2 Low Breast Cancer

A Phase 1/2a, Multicenter, Open-Label, Non-Randomized First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1303 in Patients With Advanced/Metastatic Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DB-1303, by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DB-1303 is an experimental antibody-drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05150691' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Antibody-Drug Conjugates (ADCs)</a> </li></ul>

NEAREST SITE: 342 miles Office of Dennis R. Holmes, M.D., F.A.C.S. Glendale,CA

NCT ID: NCT05218044

Cryoablation Minimally Invasive Alternative to Surgery for Women with DCIS

Cryoablation as a Minimally Invasive Alternative to Surgery for Managing Ductal Carcinoma In Situ Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cryoablation, 1 time</li> </ul> <p class="seamTextPara"> followed 6 months later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Biopsy</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cryoablation is an experimental minimally invasive, cost effective alternative to surgery that is currently being evaluated for early stage breast cancer.</li> <li class="seamTextUnorderedListItem">Cryoablation involves insertion of a probe into the breast that freezes and destroys the abnormal tissue.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05218044' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://helenreybreastcancerfoundation.com/dcis-cryoablation-study' target='_blank'>Helen Rey Breast Cancer Foundation: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cryoablation' target='_blank'>National Cancer Institute: Cryoablation</a> </li></ul>

NCT ID: NCT05386108

Elacestrant Hormone Therapy and Abemaciclib CDK 4/6 Inhibitor for ER+, HER2- Breast Cancer with Brain Metastasis

An Open-label Multicenter Phase 1b-2 Study of Elacestrant as Monotherapy and in Combination With Abemaciclib in Women and Men With Brain Metastasis From Estrogen Receptor Positive, HER-2 Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Elacestrant, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®)</li> <li class="seamTextUnorderedListItem">Elacestrant, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Elacestrant is an experimental hormone therapy called a selective estrogen receptor degrader (SERD). SERDs work by binding to and breaking down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®) is a type of targeted therapy called a CDK 4/6 inhibitor. CDK 4/6 inhibitors block two proteins, CDK4 and CDK6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women and men will also be given a drug that will put women in temporary menopause.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05386108' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.onclive.com/view/benefit-of-elacestrant-improves-with-longer-duration-of-cdk4-6-inhibition-in-patients-with-er-her2-metastatic-breast-cancer' target='_blank'>OncLive: Benefit of Elacestrant Improves With Longer Duration of CDK4/6 Inhibition in People With ER+/HER2- Metastatic Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.targetedonc.com/view/the-emerald-trial-elacestrant-mechanism-of-action-study-design-and-outcomes' target='_blank'>Targeted Oncology: Elacestrant for ER+, HER2- MBC</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/verzenio' target='_blank'>Breastcancer.org: Abemaciclib (Verzenio®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/oral-serds/' target='_blank'>Metastatic Trial Talk: Update on Oral SERDs for Estrogen Receptor-Positive MBC</a> </li></ul>

NEAREST SITE: 342 miles Clinical Trial Site Los Angeles,CA

NCT ID: NCT06016738

Palazestrant Hormone Therapy for Advanced ER+, HER2- Breast Cancer

A Phase 3 Randomized, Open-Label Study Of OP-1250 Monotherapy vs Standard of Care for the Treatment of ER+, HER2- Advanced or Metastatic Breast Cancer Following Endocrine and CDK 4/6 Inhibitor Therapy (OPERA-01) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Palazestrant (OP-1250)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Standard of care hormone therapy: fulvestrant (Faslodex®), anastrozole (Arimidex®), letrozole (Femara®), or exemestane (Aromasin®)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Palazestrant (OP-1250) and fulvestrant (Faslodex®) are types of hormone therapy called selective estrogen receptor degraders (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is approved, and palazestrant (OP-1250) is experimental.</li> <li class="seamTextUnorderedListItem">Anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®) are types of hormone therapy called aromatase inhibitors. Aromatase inhibitors block some production of estrogen that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women and men will also be given a drug that will put women in temporary menopause.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06016738' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://olema.com/pipeline/' target='_blank'>Olema Pharmaceuticals: Palazestrant (OP-1250) Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/aromatase-inhibitors' target='_blank'>Breastcancer.org: Aromatase Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/oral-serds/' target='_blank'>Metastatic Trial Talk: Update on Oral SERDs for Estrogen Receptor-Positive MBC</a> </li></ul>

NEAREST SITE: 343 miles Keck Medicine of USC Koreatown Los Angeles,CA

NCT ID: NCT05372640

ZEN003694 and Abemaciclib Targeted Therapies for Advanced Breast Cancer

A Phase 1 Study of BET Bromodomain Inhibitor ZEN003694 in Combination With the CDK4/6 Inhibitor Abemaciclib in Patients With NUT Carcinoma, Breast Cancer and Other Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ZEN003694, by mouth, daily, 5 days on, 2 days off</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ZEN003694 is an experimental targeted therapy called a BET bromodomain inhibitor. It may prevent the growth of tumor cells that overproduce BET protein.</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®) is a type of targeted therapy called a CDK4/6 inhibitor. CDK4/6 inhibitors block two proteins, CDK4 and CDK6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05372640' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.zenithepigenetics.com/programs/pipeline' target='_blank'>Zenith Epigenetics Drug Information Page: ZEN-3694</a> </li></ul>

NEAREST SITE: 348 miles USC/Norris Comprehensive Cancer Center Los Angeles,CA

NCT ID: NCT04333706

Sarilumab Immunotherapy with Chemotherapy After Surgery for Stage I-III Triple Negative Breast Cancer

A Dose Finding Phase 1 of Sarilumab Plus Capecitabine in HER2/Neu-Negative Metastatic Breast Cancer and a Single-arm, Historically-controlled Phase 2 Study of Sarilumab Plus Capecitabine in Stage I-III Triple Negative Breast Cancer With High-Risk Residual Disease (EMPOWER) Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Sarilumab (Kevzara®), by injection, every 3 weeks, up to 3 months</li> <li class="seamTextUnorderedListItem">Capecitabine (Xeloda®), by mouth, daily, 2 weeks on, 1 week off, up to 6 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Capecitabine (Xeloda®), by mouth, daily, 2 weeks on, 1 week off, up to 6 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Capecitabine (Xeloda®) is a chemotherapy commonly used to treat breast cancer.</li> <li class="seamTextUnorderedListItem">Sarilumab (Kevzara®) is approved to treat people with certain types of arthritis. Its use in breast cancer is considered experimental.</li> <li class="seamTextUnorderedListItem">Sarilumab (Kevzara®) targets a molecule made by the immune system and may have anti-cancer effects.</li> <li class="seamTextUnorderedListItem">Residual disease is cancer that remains after surgery.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04333706' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a617032.html' target='_blank'>Medline Plus: Sarilumab Drug Information Page</a> </li></ul>

NEAREST SITE: 348 miles USC Norris Comprehensive Cancer Center Los Angeles,CA

NCT ID: NCT04585750

Targeted Therapy for Advanced Breast Cancer With a TP53 Y220C Mutation

A Phase 1/2 Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation (PYNNACLE) Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PC14586, by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PC14586, by mouth, daily</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PC14586 is an experimental targeted therapy called a p53 reactivator which may stop the mutated p53 protein from working and cause cancer cell death.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: TP53 Y220C</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04585750' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.pmvpharma.com/pipeline/' target='_blank'>PMV Pharmaceuticals: PC14586 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li></ul>

VISITS: 7 visits every 3 weeks for 3 months

NCT ID: NCT04616248

Immunotherapy and Radiation Therapy for Metastatic HER2 Negative Breast Cancer

A Phase I Study of In Situ Immunomodulation With CDX-301, Radiotherapy, CDX-1140, and Poly-ICLC in Patients With Unresectable and Metastatic Solid Tumors With Injectable Palpable Disease Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CDX-301, by injection, 5 days every 3 weeks for 3 months</li> </ul> <p class="seamTextPara"> followed 3-4 days later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Radiation, 1 day every 3 weeks for 3 months</li> </ul> <p class="seamTextPara"> followed 1 day later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CDX-1140, by infusion and/or injection, 1 day every 3 weeks for 3 months</li> <li class="seamTextUnorderedListItem">Poly ICLC (Hiltonol®), by injection, 1 day every 3 weeks for 3 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CDX-301 is an experimental immunotherapy called a Flt3 agonist, which means it binds to Flt3 on immune cells to target and kill cancer cells.</li> <li class="seamTextUnorderedListItem">CDX-1140 is an experimental immunotherapy called a CD40 agonist, which means it binds to CD40 on immune cells to target and kill cancer cells.</li> <li class="seamTextUnorderedListItem">Poly ICLC (Hiltonol®) is an immunotherapy that stimulates immune cells to go after and kill cancer cells.</li> <li class="seamTextUnorderedListItem">Radiation therapy uses high-energy x-rays to damage cancer cell DNA. These x-rays stop cancer cells from dividing and growing, thus slowing or stopping tumor growth.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04616248' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/recombinant-flt3-ligand' target='_blank'>National Cancer Institute: CDX-301</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/anti-cd40-agonist-monoclonal-antibody-cdx-1140' target='_blank'>National Cancer Institute: CDX-1140</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-terms/def/poly-iclc' target='_blank'>National Cancer Institute: Poly ICLC (Hiltonol®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.oncovir.com/science' target='_blank'>Oncovir: Poly ICLC (Hiltonol®) Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/radiation-therapy' target='_blank'>Breastcancer.org: Radiation Therapy</a> </li></ul>

NEAREST SITE: 348 miles USC / Norris Comprehensive Cancer Center Los Angeles,CA

NCT ID: NCT04711109

Denosumab to Prevent Breast Cancer in Women With an Inherited BRCA1 Mutation

BRCA-P: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, International Phase 3 Study to Determine the Preventive Effect of Denosumab on Breast Cancer in Women Carrying a BRCA1 Germline Mutation Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Denosumab, by injection, every 6 months for up to 5 years</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for denosumab, by injection, every 6 months for up to 5 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Denosumab is a targeted therapy called a RANK ligand inhibitor. It is used to reduce the risk of bone fractures in people without cancer and to reduce new bone growth in people whose cancer has spread to their bones.</li> <li class="seamTextUnorderedListItem">Denosumab may also reduce the risk of developing breast cancer in women with an inherited (germline) BRCA1 mutation.</li> <li class="seamTextUnorderedListItem">Targets or mutations: BRCA1, BRCA 1</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04711109' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancerpreventioninitiative.org/projects/prevention-of-breast-cancer-by-denosumab-in-women-carrying-a-brca1-or-brca2-mutation-brca-p-trial/' target='_blank'>Cancer Prevention Initiative: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a610023.html' target='_blank'>MedlinePlus: Denosumab</a> </li></ul>

NEAREST SITE: 348 miles Keck Medicine of USC Los Angeles,CA

NCT ID: NCT05453825

Navicixizumab Targeted Therapy for Advanced Triple Negative Breast Cancer

A Phase 2, Multicenter, Open-Label Basket Study of Navicixizumab Monotherapy or in Combination With Paclitaxel or Irinotecan in Patients With Select Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Navicixizumab, every 2 weeks</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), weekly</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Navicixizumab, every 2 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Daily blood pressure measurements</li> <li class="seamTextUnorderedListItem">CT scans</li> <li class="seamTextUnorderedListItem">ECG tests</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Navicixizumab is an experimental targeted therapy called a bispecific antibody.</li> <li class="seamTextUnorderedListItem">A bispecific antibody binds to two distinct targets and may work better than traditional antibody drugs.</li> <li class="seamTextUnorderedListItem">Navicixizumab targets both DLL4 and VEGF.</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®) is a chemotherapy drug.</li> <li class="seamTextUnorderedListItem">A computed tomography (CT) scan produces body pictures created by x-ray energy.</li> <li class="seamTextUnorderedListItem">An electrocardiogram (ECG) test records electrical signals in your heart.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05453825' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://oncxerna.com/programs/' target='_blank'>OncXerna Theraputics Drug Information Page: Navicixizumab</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/taxol' target='_blank'>Breastcancer.org: Paclitaxel (Taxol®)</a> </li></ul>

NEAREST SITE: 348 miles University of Southern California, Norris Comprehensive Cancer Center Los Angeles,CA

NCT ID: NCT05683418

TOS-358 Targeted Therapy for Advanced HER2- Breast Cancer With a PIK3CA Mutation

A Study to Evaluate the Safety and Tolerability of the Covalent Phosphoinositide-3-Kinase (PI3K)-Alpha Inhibitor, TOS-358, in Adult Subjects With Select Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">TOS-358, by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">TOS-358 is an experimental targeted therapy called a PI3K inhibitor.</li> <li class="seamTextUnorderedListItem">If there is a mutation in the PIK3CA gene, the PI3K pathway can become overactivated, allowing cancer cells to grow. TOS-358 may slow or stop cancer cells from growing by blocking this pathway.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: PIK3CA</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05683418' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.totusmedicines.com/pipeline' target='_blank'>Totus Medicines: TOS-358 Drug Information Page</a> </li></ul>

NCT ID: NCT05848739

ST316 Targeted Therapy for Advanced Triple Negative Breast Cancer

A Phase 1-2 Dose-escalation and Expansion Study of ST316 in Subjects With Selected Advanced Unresectable and Metastatic Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ST316, by IV, weekly</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ST316 is an experimental Wnt/b-catenin inhibitor. Blocking Wnt/b-catenin may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05848739' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 348 miles Los Angeles County-USC Medical Center Los Angeles,CA

NCT ID: NCT06171607

Contrast-Enhanced Ultrasound to Identify Breast Masses

Characterizing Breast Masses Using an Integrative Framework of Machine Learning and Radiomics Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Contrast-enhanced ultrasound (CEUS) scan with Lumason or DEFINITY contrast agent, by IV, 1 time</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ultrasounds use sound waves to produce images of structures within your body without using radiation. Ultrasounds are widely used to diagnose many diseases in the body.</li> <li class="seamTextUnorderedListItem">A contrast-enhanced ultrasound (CEUS) is an ultrasound given with a contrast agent that helps improve images obtained from the scan.</li> <li class="seamTextUnorderedListItem">In this trial, Lumason and Perflutren are the contrast agents.</li> <li class="seamTextUnorderedListItem">The scan will take 1-1.5 hours.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06171607' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/screening-testing/breast-biopsy' target='_blank'>Breastcancer.org: Breast Biopsies</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mayoclinic.org/drugs-supplements/perflutren-lipid-microsphere-intravenous-route/side-effects/drg-20067608?p=1' target='_blank'>Mayo Clinic: Perflutren Ultrasound Contrast Agent</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mayoclinic.org/drugs-supplements/sulfur-hexafluoride-lipid-type-a-microspheres-injection-route-intravenous-route/side-effects/drg-20405988?p=1' target='_blank'>Mayo Clinic: Lumason Ultrasound Contrast Agent</a> </li></ul>

NCT ID: NCT06299163

NM32-2668 Trispecific Antibody for Advanced ROR Expressing Breast Cancer

A Phase 1 Study of NM32-2668 (Anti-ROR1/CD3/Anti-HSA Tri-Specific Antibody) in Adult Patients With Selected Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NM32-2668</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NM32-2668 is an experimental immunotherapy called a trispecific antibody.</li> <li class="seamTextUnorderedListItem">A trispecific antibody binds to 3 distinct targets and may work better than traditional antibody drugs.</li> <li class="seamTextUnorderedListItem">NM32-2668 is a bispecific antibody that targets ROR1, CD3, and HSA.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06299163' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://numab.com/pipeline/' target='_blank'>Numab Therapeutics: NM32-2668 Drug Information Page</a> </li></ul>

NEAREST SITE: 350 miles Herald Cancer Association Los Angeles,CA

NCT ID: NCT02946697

A Social Support Program Developed for Chinese-Speaking Breast Cancer Survivors

A Culturally Sensitive Social Support Intervention Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Culturally-Based Social Support Program</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Education and peer-support program, 7 weeks</li> <li class="seamTextUnorderedListItem">Receive weekly phone calls from peer-mentor</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Wait List</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Usual care (no intervention)</li> <li class="seamTextUnorderedListItem">Option to participate in the education and peer-support program after 7 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The program will address topics including treatment-related side effects, symptoms of cancer recurrence, physical therapy and other complementary treatments, stress, depression and other emotional problems, communicating with family members, and body image. </li> <li class="seamTextUnorderedListItem">Each study participant will have the opportunity to establish a relationship with a peer-mentor who is also a Chinese-speaking breast cancer survivor.</li> </ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02946697' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 350 miles OPN Healthcare Arcadia,CA

NCT ID: NCT05596409

Elacestrant Hormone Therapy for Advanced ER+, HER2- Breast Cancer

ELACESTRANT in Women and Men With CDK4/6 Inhibitor-Naive Estrogen Receptor Positive, HER-2 Negative Metastatic Breast Cancer: An Open-Label Multicenter Phase 2 Study (ELCIN) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Elacestrant (Orserdu®), by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Elacestrant is a hormone therapy called a selective estrogen receptor degrader (SERD). SERDs work by binding to and breaking down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women and men will also be given a drug that will put women in temporary menopause.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05596409' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/orserdu' target='_blank'>Breastcancer.org: Elacestrant (Orserdu®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/oral-serds/' target='_blank'>Metastatic Trial Talk: Update on Oral SERDs for Estrogen Receptor-Positive MBC</a> </li></ul>

NEAREST SITE: 353 miles City of Hope Medical Center Duarte,CA

VISITS: Every 3 weeks, ongoing

NCT ID: NCT02778685

Femara, Palbociclib, & Pembrolizumab for Metastatic ER Positive, HER2 Negative Breast Cancer

Phase II Study of the Addition of MK-3475 (Pembrolizumab) to Letrozole and Palbociclib in Patients With Metastatic Estrogen Receptor Positive Breast Cancer Who Have Stable Disease But Are Not Responding to Letrozole and Palbociclib Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Letrozole (Femara®), by mouth, daily</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), by mouth, daily (3 weeks on, 1 week off)</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Letrozole (Femara®) and palbociclib (Ibrance®) are an already approved therapy combination. </li> <li class="seamTextUnorderedListItem">Letrozole (Femara®) is an anti-estrogen therapy. </li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®) is a CDK 4/6 inhibitor, which is a type of targeted therapy. </li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a checkpoint inhibitor. It gets the immune system to go after cancer cells by blocking the protein PD-1.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02778685' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://en.wikipedia.org/wiki/Palbociclib' target='_blank'>Wikipedia: Palbociclib</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.ibrance.com' target='_blank'>Pfizer Oncology Drug Information Page: Ibrance® (Palbociclib)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.keytruda.com/?src=google&med=cpc&camp=Keytruda+Pan+Tumor_Brand_BRND_NA_ENGM_EXCT_TEXT_NA&adgrp=Brand+Keyword_General&kw=keytruda&utm_kxconfid=sq7irm3mh&gclid=CjwKCAjwycfkBRAFEiwAnLX5IZ2WUInCzwQ56GHMYYq-KXijoX1dzOK1O8HBbmaxajT0CPi2CbX3sRoC3A4QA' target='_blank'>Merck Oncology Drug Information Page: Keytruda® (Pembrolizumab)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.curetoday.com/articles/the-evolving-field-of-erpositive-metastatic-breast-cancer-care' target='_blank'>Cure Today: The Evolving Field of ER Positive-Metastatic BC</a> </li></ul>

NEAREST SITE: 353 miles City of Hope Duarte,CA

VISITS: 2 visits within 1.5 months

NCT ID: NCT03463954

Novilase® Laser Ablation Before Surgery for Women with Stage I-II BRCA Negative Breast Cancer

Prospective, Multicenter Confirmatory Clinical Evaluation of Novilase® Interstitial Laser Therapy for the Focal Destruction of Malignant Breast Tumors ≤15 mm (BR-003) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Novilase® laser ablation</li> </ul> <p class="seamTextPara"> followed 1-1.5 months later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Surgery to remove tumor</li> <li class="seamTextUnorderedListItem">MRI scan</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The Novilase® laser ablation system kills tumor cells by heating the tissue with a laser.</li> <li class="seamTextUnorderedListItem">A magnetic resonance imaging (MRI) scan produces body pictures created by using magnetic energy rather than x-ray energy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03463954' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://novilase.com/' target='_blank'>Novian Health: Novilase®</a> </li></ul>

NCT ID: NCT03696030

CAR T-Cell Immunotherapy in HER2+ Breast Cancer with Brain or Leptomeningeal Metastases

A Phase 1 Cellular Immunotherapy Study of Intraventricularly Administered Autologous HER2-Targeted Chimeric Antigen Receptor (HER2-CAR) T Cells in Patients With Brain and/or Leptomeningeal Metastases From HER2 Positive Cancers Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Blood draw to collect white blood cells to make your HER2 CAR T-cell therapy (leukapheresis)</li> <li class="seamTextUnorderedListItem">Surgery to place a device (similar to a chemotherapy port) under your scalp</li> <li class="seamTextUnorderedListItem">HER2 CAR T-cells, by injection, weekly, 3 times</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule. Hospital stay may be required.</i> </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Follow up</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Every 2 months for 1 year, then every year for 15 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Leptomeningeal metastases are when cancer spreads to the membranes surrounding the brain and/or the spinal cord (leptomeninges) or to the cerebrospinal fluid.</li> <li class="seamTextUnorderedListItem">CAR-T or CAR T cell therapy is a personalized immunotherapy made from your white blood cells.</li> <li class="seamTextUnorderedListItem">Your blood cells are removed and modified in a lab with chimeric antigen receptors (CARs) so that they can attack a specific protein.</li> <li class="seamTextUnorderedListItem">The CAR T-cells are then infused back into you while you are hospitalized. </li> <li class="seamTextUnorderedListItem">The CAR T-cell therapy being used in this study trains the immune system to attack HER2+ cancer cells.</li> <li class="seamTextUnorderedListItem">You will have surgery to insert a device under your scalp so that the CAR T-cell therapy can be infused directly into your brain.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03696030' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cityofhope.org/physician-news/breast-cancer-car-t-cell-therapy' target='_blank'>City of Hope Trial Information</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-terms/def/car-t-cell-therapy' target='_blank'>NCI Dictionary of Cancer Terms: CAR T-cell Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/car-t-cell1.html' target='_blank'>American Cancer Society: CAR T-cell Therapy and Its Side Effects</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/from-the-experts/what-is-car-t-therapy/' target='_blank'>Metastatic Trial Talk: What is CAR-T Therapy?</a> </li><li class='seamTextUnorderedListItem'><a href='http://mbcn.org/brain-mets/' target='_blank'>Metastatic Breast Cancer Network: Brain Metastases</a> </li></ul>

NCT ID: NCT03746431

Radiopharmaceutical and Targeted Therapy for HER2 Negative Breast Cancer

A Phase 1/2 Study of [225Ac]-FPI-1434 Injection in Patients With Locally Advanced or Metastatic Solid Tumours Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">225Ac-FPI-1434, by injection, multiple doses</li> <li class="seamTextUnorderedListItem">111In-FPI-1547, by injection</li> <li class="seamTextUnorderedListItem">FPI-1175, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">225Ac-FPI-1434 is an experimental radiation therapy drug called a radioimmuno-therapeutic agent, radiopharmaceutical, or radioactive drug.</li> <li class="seamTextUnorderedListItem">111In-FPI-1547 is a radioimmuno-imaging agent that helps doctors visualize cancer cells.</li> <li class="seamTextUnorderedListItem">FPI-1175 is an experimental targeted therapy called a IGF-1R inhibitor. Blocking IGF-1R may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03746431' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://fusionpharma.com/fusion-pipeline/' target='_blank'>Fusion Pharmaceuticals Drug Information Page: 225Ac-FPI-1434</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/news-events/cancer-currents-blog/2020/radiopharmaceuticals-cancer-radiation-therapy' target='_blank'>National Cancer Institute: Radiopharmaceuticals</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/actinium-ac-225-fpi-1434' target='_blank'>National Cancer Institute: 225Ac-FPI-1434</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/indium-in-111-fpi-1547' target='_blank'>National Cancer Institute: 111In-FPI-1547</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy' target='_blank'>Breastcancer.org: Targeted Therapy</a> </li></ul>

NCT ID: NCT04020575

CAR T-Cell Immunotherapy for Metastatic Breast Cancer That Tests Positive for MUC 1*

Adoptive Immunotherapy for Advanced MUC1* Positive Breast Cancer With Autologous T Cells Engineered to Express a Chimeric Antigen Receptor, huMNC2-CAR44 Specific for a Cleaved Form of MUC1 (MUC1*) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Blood draw to collect white blood cells to make your personalized CAR T-cell therapy (leukapheresis)</li> <li class="seamTextUnorderedListItem">Chemotherapy to deplete your lymph cells</li> <li class="seamTextUnorderedListItem">huMNC2-CAR44 CAR T-cells, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule. Hospital stay may be required.</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CAR T cell or CAR-T cell therapy is a personalized immunotherapy made from your white blood cells. </li> <li class="seamTextUnorderedListItem">Your blood cells are removed and modified in a lab with chimeric antigen receptors (CARs) so that they can attack a specific protein. </li> <li class="seamTextUnorderedListItem">The CAR T-cells are then infused back into you while you are hospitalized </li> <li class="seamTextUnorderedListItem">The CAR T-cell therapy being used in this study trains the immune system to attack MUC1 on cancer cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04020575' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mdanderson.org/treatment-options/car-t-cell-therapy.html' target='_blank'>MD Anderson Cancer Center: CAR T-Cell Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/about-cancer/treatment/research/car-t-cells' target='_blank'>NCI: Car T-Cells</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.minervabio.com/clinical-trial-humnc2-car44-in-mbc/' target='_blank'>Minerva Biotechnologies: Study Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/from-the-experts/what-is-car-t-therapy/' target='_blank'>Metastatic Trial Talk: What is CAR-T Therapy?</a> </li></ul>

NCT ID: NCT04305834

Effects of Abemaciclib in People 70 or Older With Metastatic Hormone Positive Breast Cancer

A Phase IIA Trial Assessing the Tolerability of Abemaciclib Monotherapy in Patients Age 70 and Older With Hormone Receptor Positive Metastatic Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, daily, ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®) is a CDK 4/6 inhibitor that is commonly used to treat metastatic, hormone positive (ER+ and/or PR+) breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04305834' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.verzenio.com' target='_blank'>Drug Company Information Page: Verzenio® (Abemaciclib)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted_therapies/verzenio' target='_blank'>Breastcancer.org: Abemaciclib (Verzenio®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.bcrf.org/blog/breast-cancer-elderly-how-bcrf-researchers-are-treating-growing-patient-population' target='_blank'>Breast Cancer Research Foundation: Breast Cancer in the Elderly</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249663/' target='_blank'>Journal Article: Use of Cyclin-Dependent Kinase 4/6 (CDK4/6) Inhibitors in Older Patients</a> </li></ul>

NCT ID: NCT04699630

Antibody-Drug Conjugate U3-1402 for Advanced HER2 Negative Breast Cancer

A Phase II Study of U3-1402 in Patients With Metastatic Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">U3-1402, by IV, every 3 weeks, ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Antibody-drug conjugates (ADCs) are therapies that contain an antibody linked to a specific type of chemotherapy. They are designed to deliver high doses of chemotherapy to cancer cells while sparing normal cells. </li> <li class="seamTextUnorderedListItem">U3-1402 is an investigational antibody-drug conjugate -- this means it is only available in clinical trials. </li> <li class="seamTextUnorderedListItem">U3-1402 targets HER3 to deliver chemotherapy directly to cancer cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04699630' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Getting to the Target, Antibody-Drug Conjugates</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/patritumab-deruxtecan' target='_blank'>NCI Drug Dictionary: U3-1402</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.annalsofoncology.org/article/S0923-7534(19)30419-3/fulltext' target='_blank'>Annals of Oncology: Single Agent Activity of U3-1402</a> </li></ul>

NEAREST SITE: 353 miles City of Hope Comprehensive Cancer Center Duarte,CA

VISITS: At least every 3 weeks

NCT ID: NCT05070247

TAK-500 ADC with Pembrolizumab for Advanced Triple Negative Breast Cancer

An Open-label, Dose Escalation and Expansion, Phase 1a/1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-500, a Novel Stimulator of Interferon Genes Agonist, as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Select Locally Advanced or Metastatic Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">TAK-500, by IV, every 2 or 3 weeks</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">TAK-500 is an experimental type of targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Its antibody targets and activates STING, a pathway that activates the immune system to attack cancer cells, and it delivers an anti-cancer drug called TAK-676.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05070247' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.takeda.com/49c795/siteassets/system/investors/investor--events/asco-2021-ir-event_en.pdf' target='_blank'>Takeda Drug Information Presentation (Slide 23): TAK-500</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Antibody-Drug Conjugates</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li></ul>

NCT ID: NCT05238922

INCB123667 Targeted Therapy for Advanced Breast Cancer

A Phase 1, Open-Label, Multicenter Study of INCB123667 as Monotherapy in Participants With Selected Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">INCB0123667, by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">May require at least 1 biopsy</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">INCB123667 is an experimental type of targeted therapy called a CDK 2/CDK2 inhibitor.</li> <li class="seamTextUnorderedListItem">CDK 2 inhibitors block the enzyme/protein CDK2 that helps cancer grow.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05238922' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.incyteclinicaltrials.com/study/?id=INCB%20123667-101' target='_blank'>Incyte Corporation Clinical Trial Page: INCB123667</a> </li><li class='seamTextUnorderedListItem'><a href='https://investor.incyte.com/news-releases/news-release-details/incyte-reports-2022-first-quarter-financial-results-and-provides' target='_blank'>Incyte Corporation Press Release: INCB123667</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.org/cancer/breast-cancer/treatment/targeted-therapy-for-breast-cancer.html' target='_blank'>American Cancer Society: CDK Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/what-are-cdk46-inhibitors' target='_blank'>Breastcancer.org: CDK 4/6 Inhibitors</a> </li></ul>

NEAREST SITE: 353 miles City of Hope National Medical Center Duarte,CA

NCT ID: NCT05325866

Bemarituzumab Targeted Therapy for Advanced Triple Negative Breast Cancer that Expresses FGFR2b

A Phase 1b/2, Multicenter, Open-label Basket Study Evaluating the Safety and Efficacy of Bemarituzumab Monotherapy in Solid Tumors With FGFR2b Overexpression (FORTITUDE-301) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Bemarituzumab (AMG 552), by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Bemarituzumab (AMG 552) is an experimental targeted therapy called a FGFR2b inhibitor. Targeting FGFR2b may slow or stop cancer cell growth.</li> <li class="seamTextUnorderedListItem">This type of study is called a basket trial. It is enrolling people with other types of cancer based on the kind of mutations found in their tumors.</li> <li class="seamTextUnorderedListItem">Targets or mutations: FGFR2b, FGFR</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05325866' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.amgenpipeline.com/' target='_blank'>Amgen Drug Information Page: Bemarituzumab</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy' target='_blank'>Breastcancer.org: Targeted Therapy</a> </li></ul>

NCT ID: NCT05340673

Aquaphor and Miaderm for Radiation Dermatitis

A Randomized Clinical Trial Comparing Supplemental Topical Treatments for Acute Radiation Dermatitis in Breast Cancer Patients Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Aquaphor, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Miaderm, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Radiation dermatitis is a radiation-induced skin reaction that can cause itching, swelling, pain, and general discomfort.</li> <li class="seamTextUnorderedListItem">Aquaphor and Miaderm are 2 supplemental topical agents commonly recommended and used by people with breast cancer undergoing external beam radiation therapy (EBRT).</li> <li class="seamTextUnorderedListItem">Aquaphor is a commonly available, inexpensive, petrolatum-based multi-purpose ointment designed to protect and sooth extremely dry skin, chapped lips, cracked hands and feet, minor cuts and burns, and many other skin irritations.</li> <li class="seamTextUnorderedListItem">Miaderm is a water-based cream and contains ingredients like calendula, hyaluronate, and aloe vera which may help reduce occurrence and severity of radiation dermatitis.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05340673' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://my.clevelandclinic.org/health/diseases/21995-radiation-burns#:~:text=Radiation%20burn%20or%20radiation%20dermatitis,peel%2C%20itch%20or%20turn%20red.' target='_blank'>Cleveland Clinic: Radiation Dermatitis</a> </li></ul>

NCT ID: NCT05346484

Oncolytic Virus Alone or With Pembrolizumab for People with Advanced Breast Cancer

A Phase I, Dose Escalation Safety and Tolerability Study of VAXINIA (CF33-hNIS), Administered Intratumorally or Intravenously as a Monotherapy or in Combination With Pembrolizumab in Adult Patients With Metastatic or Advanced Solid Tumors (MAST).(VAXINIA) Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CF33-hNIS, by injection or IV, 2 times in 3 weeks, then every 3 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CF33-hNIS, by injection or IV, 2 times in 3 weeks, then every 3 weeks</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CF33-hNIS is an experimental immunotherapy called an oncolytic virus. Oncolytic viruses are a form of immunotherapy that uses viruses to infect and destroy cancer cells.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05346484' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.imugene.com/oncolytic-virus' target='_blank'>Imugene: CF33-hNIS Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancerresearch.org/treatment-types/oncolytic-virus-therapy' target='_blank'>Cancer Research Institute: Oncolytic Viruses</a> </li></ul>

VISITS: 1 visit every 1-2 months

NCT ID: NCT05376878

PET/MRI Scan to Determine Response to Treatment for People with Metastatic HER2+ Breast Cancer with Brain or Leptomeninges Metastasis

Pilot Study to Evaluate 64Cu-DOTA-Trastuzumab Imaging in Patients With HER2+ Breast Cancer With Brain Metastatsis Treated With Fam-Trastuzumab Deruxtecan Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®), by IV, 1 time</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">64Cu-DOTA-trastuzumab, by IV, 1 time</li> <li class="seamTextUnorderedListItem">PET/MRI scan, 1 time</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Brain MRI scan, every 1.5 months for 6 months, then every 2 months</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (Enhertu®), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">64Cu-DOTA-trastuzumab is an experimental tracer that detects cancer cells during imaging scans.</li> <li class="seamTextUnorderedListItem">A positron emission tomography (PET) scan is an imaging test that uses a radioactive tracer to look for and attach to cancer cells.</li> <li class="seamTextUnorderedListItem">A magnetic resonance imaging (MRI) scan produces body pictures created by using magnetic energy.</li> <li class="seamTextUnorderedListItem">The results of your PET/MRI scan will find the cancer in your brain and may predict your response to treatment.</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®) is a type of anti-HER2 targeted therapy used to treat HER2+ breast cancer.</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (Enhertu®) is an antibody-drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (Enhertu®)'s antibody targets HER2 and delivers an anti-cancer drug called deruxtecan.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05376878' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cedars-sinai.org/programs/imaging-center/exams/nuclear-medicine/pet-mri.html' target='_blank'>Cedars-Sinai: PET/MRI Scan</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/herceptin' target='_blank'>Breastcancer.org: Trastuzumab (Herceptin®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/enhertu' target='_blank'>Breastcancer.org: Trastuzumab deruxtecan (Enhertu®)</a> </li></ul>

VISITS: 1 visit every day for 5 days, then every 6-12 months for 3 years

NCT ID: NCT06008158

Accelerated Partial Breast Irradiation After Surgery for Women with DCIS or Stage I ER+, HER2- Breast Cancer

Prospective Evaluation of a Once Per Day Regimen of Accelerated Partial Breast Irradiation in Low-Risk, Hormone-Responsive Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Accelerated partial breast irradiation, daily for 5 days</li> <li class="seamTextUnorderedListItem">Follow-up visits, 10 times over 3 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Accelerated partial breast irradiation (APBI) is a type of radiation therapy that delivers radiation only to the part of the breast with cancer.</li> <li class="seamTextUnorderedListItem">APBI is given in a shorter course of treatment than whole breast radiation therapy, over a few days instead of several weeks, with a lower total dose of radiation.</li> <li class="seamTextUnorderedListItem">A lumpectomy is also called a partial mastectomy.</li> <li class="seamTextUnorderedListItem">Node negative means cancer has not spread to your lymph nodes.</li> <li class="seamTextUnorderedListItem">A margin that does not contain tumor cells is called a negative margin and tells the surgeon that the tumor has been removed. A positive margin contains tumor cells at or near the edge of the tissue removed.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06008158' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.moffitt.org/treatments/radiation-therapy/apbi-accelerated-partial-breast-irradiation/' target='_blank'>Moffitt Cancer Center: Accelerated Partial Breast Irradiation</a> </li></ul>

VISITS: 5 visits within 6 months

NCT ID: NCT06042569

Lower Chemotherapy Doses for Older Women with Stage I-III HER2 Negative Breast Cancer

Dose Reduction of Docetaxel-Based Chemotherapy in Vulnerable Older Women With Early-Stage Breast Cancer (DOROTHY) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Lower dose docetaxel (Taxotere®), by IV, every 3 weeks for 3 months</li> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®), by IV, every 3 weeks for 3 months </li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Standard dose docetaxel (Taxotere®), by IV, every 3 weeks for 3 months</li> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®), by IV, every 3 weeks for 3 months</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Chemotherapy drugs, such as cyclophosphamide (Cytoxan®) and docetaxel (Taxotere®), work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. </li> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®) and docetaxel (Taxotere®) are not well tolerated at the standard dose and can affect the way older people feel physically and emotionally.</li> <li class="seamTextUnorderedListItem">Giving a lower dose may be an effective treatment option and improve quality of life in older women.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06042569' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/taxotere' target='_blank'>Breastcancer.org: Docetaxel (Taxotere®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/cytoxan' target='_blank'>Breastcancer.org: Cyclophosphamide (Cytoxan®)</a> </li></ul>

NEAREST SITE: 353 miles City of Hope National Medical Center /ID# 258645 Duarte,CA

NCT ID: NCT06084481

ABBV-400 ADC for Advanced Triple Negative or HR+, HER2- Breast Cancer

A Phase 1 Open-Label Study to Evaluate the Efficacy and Safety of ABBV-400 in Select Advanced Solid Tumor Indications Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ABBV-400, by IV</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ABBV-400 is an experimental targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">ABBV-400's antibody targets cMet, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06084481' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.abbvie.com/science/pipeline.html' target='_blank'>AbbVie: ABBV-400 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li></ul>

NEAREST SITE: 353 miles Apollo Investigative Site Duarte,CA

VISITS: 1 visit every 2-3 months

NCT ID: NCT06399757

APL-5125 Targeted Therapy for Advanced Triple Negative Breast Cancer

A Phase 1/2 Study to Assess the Safety and Antitumor Activity of APL-5125 in Adults With Selected Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">APL-5125, by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">APL-5125 is a type of targeted therapy called a kinase inhibitor. It blocks an enzyme that helps cancer cells grow.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06399757' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.apollotx.com/pipeline/' target='_blank'>Apollo Therapeutics: APL-5125 Drug Information Page</a> </li></ul>

NEAREST SITE: 359 miles The Oncology Institute Whittier,CA

PHASE: II-III

NCT ID: NCT05747794

Study in Metastatic Breast Cancer Patients Receiving Eftilagimod Alpha or Placebo in Combination With Paclitaxel Chemotherapy

AIPAC-003 (Active Immunotherapy and PAClitaxel): A Randomized, Double-blind, Placebo-controlled Phase 3 Trial Testing Eftilagimod Alpha (Soluble LAG-3) in HER2-neg/Low Metastatic Breast Cancer Patients Receiving Paclitaxel, Following an Open-label Dose Optimization Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Eftilagimod alpha (efti), by injection, 6 months</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV, 6 months (standard of care)</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Eftilagimod alpha (efti), by injection, 6-7 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for eftilagimod alpha (efti), by injection, 6 months</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV, 6 months (standard of care)</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for eftilagimod alpha (efti), by injection, 6-7 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Eftilagimod alpha (efti) is an experimental immunotherapy that activates the immune system to go after and kill cancer cells.</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®) is a chemotherapy drug used to treat advanced breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05747794' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.immutep.com/pipeline/clinical-pipeline.html#imp' target='_blank'>Immutep Drug Information Page: Eftilagimod Alpha (Efti)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/taxol' target='_blank'>Breastcancer.org: Paclitaxel (Taxol®)</a> </li></ul>

NEAREST SITE: 362 miles Research Site Long Beach,CA

NCT ID: NCT04964934

Camizestrant with Targeted Therapy for Advanced HR+, HER2- Breast Cancer with an ESR1 Mutation

A Phase III, Double-blind, Randomised Study to Assess Switching to AZD9833 (a Next Generation, Oral SERD) + CDK4/6 Inhibitor (Palbociclib or Abemaciclib) vs Continuing Aromatase Inhibitor (Letrozole or Anastrozole)+ CDK4/6 Inhibitor in HR+/HER2-MBC Patients With Detectable ESR1Mutation Without Disease Progression During 1L Treatment With Aromata... Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 6 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Camizestrant (AZD9833), by mouth, daily</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), by mouth, daily, 3 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Placebo, by mouth, daily </li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Camizestrant (AZD9833), by mouth, daily</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, daily, 3 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Placebo, by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for camizestrant (AZD9833), by mouth, daily</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), by mouth, daily, 3 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Anastrozole (Arimidex®), by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 4</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for camizestrant (AZD9833), by mouth, daily</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, daily, 3 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Anastrozole (Arimidex®), by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 5</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for camizestrant (AZD9833), by mouth, daily</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), by mouth, daily, 3 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Letrozole (Femara®), by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 6</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for camizestrant (AZD9833), by mouth, daily</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, daily, 3 weeks on, 1 week off</li> <li class="seamTextUnorderedListItem">Letrozole (Femara®), by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Camizestrant (AZD9833) is an experimental type of anti-estrogen therapy called a selective estrogen receptor degrader (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®) and abemaciclib (Verzenio®) are CDK4/6 inhibitors, a type of targeted therapy.</li> <li class="seamTextUnorderedListItem">CDK4/6 inhibitors block two enzymes, CDK4 and CDK6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">Letrozole (Femara®) and anastrozole (Arimidex®) are aromatase inhibitors, a type of hormone therapy.</li> <li class="seamTextUnorderedListItem">Aromatase inhibitors block some production of estrogen that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women and men will also be given a drug that will put women in temporary menopause.</li> <li class="seamTextUnorderedListItem">Targets or mutations: ESR1</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04964934' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.org/cancer/breast-cancer/treatment/hormone-therapy-for-breast-cancer.html' target='_blank'>American Cancer Society: Hormone Therapy for Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.komen.org/breast-cancer/treatment/type/cdk4-6-inhibitors/' target='_blank'>Susan G. Komen: CDK4/6 Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.komen.org/breast-cancer/treatment/type/hormone-therapy/aromatase-inhibitors/' target='_blank'>Susan G. Komen: Aromatase Inhibitors</a> </li></ul>

NEAREST SITE: 362 miles Innovative Clinical Research Institute Whittier,CA

NCT ID: NCT05593094

ZN-A-1041 Targeted Therapy for Advanced HER2 Positive or HER2 Low Breast Cancer

A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ZN-A-1041 Enteric Capsules as a Single Agent or in Combination in Patients With HER2-Positive Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 3 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ZN-A-1041, by mouth, daily</li> <li class="seamTextUnorderedListItem">Trastuzumab emtansine (T-DM1, Kadcyla®), by IV, every 3 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ZN-A-1041, by mouth, daily</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (T-Dxd), by IV, every 3 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ZN-A-1041, by mouth, daily</li> <li class="seamTextUnorderedListItem">Pertuzumab/trastuzumab (PHESGO®), by injection, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ZN-A-1041 is an experimental anti-HER2 targeted therapy called a tyrosine kinase inhibitor. It blocks an enzyme, tyrosine kinase, that helps cancer cells grow.</li> <li class="seamTextUnorderedListItem">Trastuzumab emtansine (T-DM1, Kadcyla®) and trastuzumab deruxtecan (T-Dxd, Enhertu®) are antibody drug conjugates (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Trastuzumab emtansine and trastuzumab deruxtecan target HER2 and deliver anti-cancer drugs.</li> <li class="seamTextUnorderedListItem">Pertuzumab/trastuzumab (PHESGO®) is a combination of two anti-HER2 targeted therapies, pertuzumab (Perjeta®) and trastuzumab (Herceptin®). You may also receive the two drugs separately.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 2+.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05593094' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.businesswire.com/news/home/20200907005109/en/Zion-Pharma-Announces-Initiation-of-Phase-1-Study' target='_blank'>Zion Pharma Press Release: ZN-A-1041</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/kadcyla' target='_blank'>Breastcancer.org: Trastuzumab emtansine (T-DM1, Kadcyla®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/enhertu' target='_blank'>Breastcancer.org: Trastuzumab deruxtecan (T-Dxd, Enhertu®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/phesgo' target='_blank'>Breastcancer.org: Pertuzumab/trastuzumab (PHESGO®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/what-are-anti-her2-therapies' target='_blank'>Breastcancer.org: Anti-HER2 Targeted Therapy</a> </li></ul>

NEAREST SITE: 366 miles Cancer Blood and Specialty Clinic-Research ( Site 0008) Los Alamitos,CA

VISITS: At least 1 visit every 1.5 months for 6 months

NCT ID: NCT06393374

Sacituzumab Tirumotecan ADC with Immunotherapy for Stage I-III Triple Negative Breast Cancer

A Phase 3, Randomized, Open-label, Study to Compare the Efficacy and Safety of Adjuvant MK-2870 in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice (TPC) in Participants With Triple-Negative Breast Cancer (TNBC) Who Received Neoadjuvant Therapy and Did Not Achieve a Pathological Complete Response (pCR) at Surgery (... Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 1.5 months for 6 months</li> <li class="seamTextUnorderedListItem">Sacituzumab tirumotecan (sac-TMT), by IV, every 2 weeks for 6 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV, every 1.5 months for 6 months</li> </ul> <p class="seamTextPara"> with or without: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Capecitabine (Xeloda®), by mouth, daily, 2 weeks on, 1 week off for 6 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Sacituzumab tirumotecan is a type of targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">The antibody in sacituzumab tirumotecan targets TROP2 proteins. It delivers the chemotherapy belotecan.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">Capecitabine (Xeloda®) is a chemotherapy drug.</li> <li class="seamTextUnorderedListItem">Non-pathologic complete response is the presence of cancer cells after treatment.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06393374' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.merck.com/research/product-pipeline/' target='_blank'>Merck: Sacituzumab Tirumotecan Drug Information Page</a> </li></ul>

NEAREST SITE: 374 miles UC Irvine Health/Chao Family Comprehensive Cancer Center Orange,CA

NCT ID: NCT03994796

Genetic Testing for Choosing a Targeted Therapy for Brain Metastases that Test Positive for Certain Mutations

Genomically-Guided Treatment Trial in Brain Metastases Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 3 groups depending on which genetic mutations are found in your tumors: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: CDK-mutation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, twice a day, ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: PI3K-mutation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">GDC-0084, by mouth, daily, ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3: NTRK or ROS1-mutation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Entrectinib (Rozlytrek®), by mouth, daily, ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Tumor samples from your brain and other parts of your body will be tested for mutations. This is called genomic testing.</li> <li class="seamTextUnorderedListItem">You will be assigned a targeted therapy based on which genetic mutations are found in your tumors.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer. </li> <li class="seamTextUnorderedListItem">Targets or mutations: NTRK, ROS1, CDK, PI3K</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03994796' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://mbcn.org/brain-mets/' target='_blank'>Metastatic Breast Cancer Network: Brain Mets</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.verzenio.com/hcp/patient-profiles' target='_blank'>Eli Lilly & Company Drug Information Page: Verzenio® (Abemaciclib)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.rozlytrek.com' target='_blank'>Genentech USA Drug Information Page: Rozlytrek (Entrectinib)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/pi3k-inhibitor-gdc-0084' target='_blank'>NCI Drug Dictionary: GDC-0084</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancernetwork.com/view/targeting-sanctuary-site-options-when-breast-cancer-metastasizes-brain' target='_blank'>Journal Article: Targeting the Sanctuary Site, Options when Breast Cancer Metastasizes to the Brain</a> </li></ul>

NEAREST SITE: 374 miles University of California - Irvine Medical Center Orange,CA

VISITS: 1 visit a week, ongoing

NCT ID: NCT04180371

BT5528 Alone or With Nivolumab in Advanced Triple Negative Breast Cancer That Tests EphA2+

Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT5528 in Patients With Advanced Malignancies Associated With EphA2 Expression Scientific Title

• <p class="seamTextPara"> This trial is being conducted in two parts. You will participate in 1 of 2 parts depending on when you enroll: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Part 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BT5528, by IV, once a week, ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Part 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BT5528, by IV, once a week, ongoing</li> <li class="seamTextUnorderedListItem">Nivolumab (Opdivo®), by IV, once every 4 weeks, ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BT5528 targets a protein called EphA2 that helps cancer cells grow. </li> <li class="seamTextUnorderedListItem">EphA2 is found on some triple negative breast tumors. </li> <li class="seamTextUnorderedListItem">Opdivo is a type of immunotherapy called a checkpoint inhibitor. It gets the immune system to go after cancer cells by blocking a protein called PD-1 (programmed cell death 1). It is approved to treat certain types of cancer. Its use in breast cancer is considered experimental.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04180371' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.bicycletherapeutics.com/programs/' target='_blank'>Bicycle Therapeutics Information Page: BT5528</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.nature.com/articles/onc2017170' target='_blank'>Journal Article: Targeting EphA2 In Triple Negative Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.opdivo.com/about-opdivo/how-opdivo-works-monotherapy' target='_blank'>Bristol-Meyers Squibb Information Page: Opdivo</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.curetoday.com/publications/cure/2019/immunotherapy-2019/breast-cancer-gets-a-boost-from-immunotherapy' target='_blank'>Cure Today: Breast Cancer Gets a Boost From Immunotherapy</a> </li></ul>

NEAREST SITE: 374 miles Chao Family Comprehensive Cancer Center, University of California, Irvine Orange,CA

VISITS: 2 visits in 1 month, then monthly

NCT ID: NCT05524584

Hormone Therapy and Targeted Therapy for Advanced HR+, HER2- Breast Cancer

Phase II, Open-Labeled, Single-Armed Combination Treatment With Anastrozole, Fulvestrant and Abemaciclib for Hormone Receptor Positive, HER2(-) Metastatic Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, every 2 weeks for 1 month, then monthly</li> <li class="seamTextUnorderedListItem">Anastrozole (Arimidex®), by mouth, daily</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women and men will also be given a drug that will put women in temporary menopause.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05524584' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/arimidex' target='_blank'>Breastcancer.org: Anastrozole (Arimidex®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/arimidex' target='_blank'>Breastcancer.org: Abemaciclib (Verzenio®)</a> </li></ul>

NEAREST SITE: 374 miles University of California Irvine Irvine,CA

VISITS: May require hospitalization; 1 visit every 3 weeks for 2 years

NCT ID: NCT05576077

TBio-4101 TIL Therapy with Pembrolizumab Immunotherapy for Advanced Breast Cancer

A Phase 1b Study of TBio-4101 (Autologous Selected and Expanded Tumor-Infiltrating Lymphocytes [TIL]) and Pembrolizumab in Patients With Advanced Solid Tumor Malignancies (STARLING) Scientific Title

• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®)</li> <li class="seamTextUnorderedListItem">Fludarabine (Fludara®)</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">TBio-4101</li> <li class="seamTextUnorderedListItem">IL-2</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), every 3 weeks for 2 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">TBio-4101 is an experimental immunotherapy called tumor infiltrating lymphocyte (TIL) therapy.</li> <li class="seamTextUnorderedListItem">TBio-4101 is made by collecting, growing, and modifying specialized immune cells that are collected from your tumor. The immune cells may recognize, target, and kill the tumor cells.</li> <li class="seamTextUnorderedListItem">Before you receive the immune cells, you will be treated with the chemotherapy drugs cyclophosphamide (Cytoxan®) and fludarabine (Fludara®). This is to prepare your body to receive the enhanced immune cells.</li> <li class="seamTextUnorderedListItem">IL-2 is a type of immunotherapy that activates immune cells to kill cancer cells.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05576077' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://turnstonebio.com/#our-science' target='_blank'>Turnstone Biologics: TBio-4101 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy#section-immune-targeted-therapies' target='_blank'>Breastcancer.org: Tumor Infiltrating Lymphocyte (TIL) Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/adoptive-cell-therapy-2-2/' target='_blank'>Metastatic Trial Talk: Adoptive Cell Therapies: A Type of Immunotherapy for MBC</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/immune-checkpoint-inhibitor/' target='_blank'>Metastatic Trial Talk: Update on Immunotherapy for MBC: Immune Checkpoint Inhibitors</a> </li></ul>

VISITS: 1 visit every week for 4 months

NCT ID: NCT05751668

GM1 to Reduce or Prevent Nerve Pain During Chemotherapy for Metastatic Breast Cancer

An Early Phase and Phase II Clinical Trial to Evaluate Ganglioside-Monosialic Acid (GM1) for Preventing Paclitaxel-Associated Neuropathy Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">GM1, by IV, weekly for 4 months</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV, weekly for 4 months</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Control</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for GM1, by IV, weekly for 4 months</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV, weekly for 4 months</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Neuropathy is nerve pain in your hands and feet as a side effect of cancer treatment such as chemotherapy.</li> <li class="seamTextUnorderedListItem">GM1 is a part of the body's natural system that protects nerves from damage.</li> <li class="seamTextUnorderedListItem">Chemotherapy drugs, such as paclitaxel (Taxol®), work in different ways to stop the growth of cancer cells, either by killing the cells, stopping them from dividing, or stopping them from spreading.</li> <li class="seamTextUnorderedListItem">This trial is also available in Spanish.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05751668' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/taxol' target='_blank'>Breastcancer.org: Paclitaxel (Taxol®)</a> </li></ul>

NEAREST SITE: 374 miles SystImmune Recruiting Site Orange,CA

NCT ID: NCT05983432

BL-B01D1 ADC for Advanced HER2- Breast Cancer

A Phase 1 Study Evaluating the Safety, Tolerability, and Efficacy of BL-B01D1 in Subjects With Metastatic or Unresectable Non-Small Cell Lung Cancer and Other Solid Tumors (BL-B01D1-LUNG-101) Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BL-B01D1, by IV, weekly, 2 weeks on, 1 week off</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BL-B01D1, by IV, weekly</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BL-B01D1 is an experimental targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">The antibody in BL-B01D1 targets EGFR and HER3 proteins and delivers a chemotherapy drug.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05983432' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://systimmune.com/bl-m01d1' target='_blank'>SystImmune: BL-B01D1 Drug Information Page</a> </li></ul>

NEAREST SITE: 375 miles Knowledge Research Center Orange,CA

VISITS: 2 times within 6 months, then 3 times within 2 years

NCT ID: NCT04638751

Stool and Blood Sample Bank to Develop New Treatments for Triple Negative Breast Cancer

ARGONAUT: Development and Analysis of a Blood and Stool Sample Bank for Cancer Patients, Enabling the Systematic Study of the Effect of Gut Microbiomes on Response to Treatment Scientific Title

• <p class="seamTextPara"> You will provide the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stool and blood samples, 2 times within 6 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stool samples will be used to study your gut microbiome, which are the microorganisms that live in your digestive system. Drugs that target your microbiome may be helpful to treat cancer.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04638751' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.healthline.com/nutrition/gut-microbiome-and-health' target='_blank'>Healthline: Gut Microbiome</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.aiche.org/resources/publications/cep/2020/october/developing-precision-microbiome-medicines' target='_blank'>American Institute of Chemical Engineers: Developing Precision Microbiome Medicines</a> </li></ul>

NEAREST SITE: 381 miles Hoag Memorial Hospital Presbyterian Newport,CA

NCT ID: NCT05455619

Evexomostat for Women with Advanced HR+, HER2- Breast Cancer with a PIK3CA Mutation and High Blood Sugar

Phase 1b/2 Study of the Safety and Efficacy of Evexomostat Plus Alpelisib and Fulvestrant in Postmenopausal Women at Risk for Hyperglycemia With Advanced Breast Cancer and a PIK3CA Mutation Following Endocrine Therapy and a CDK4/6 Inhibitor Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Evexomostat (SDX-7320)</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®)</li> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Evexomostat (SDX-7320) is an experimental polymer drug conjugate (PDC), which is similar to an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">Evexomostat (SDX-7320) releases fumagillol, a type of targeted therapy called a MetAP2 inhibitor. Blocking MetAP2 may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor downregulator (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®) is a type of targeted therapy called a PI3K inhibitor. Blocking the PI3K pathway may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women will also be given a drug that will put women in temporary menopause.</li> <li class="seamTextUnorderedListItem">Targets or mutations: PIK3CA</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05455619' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.amelia1.com/' target='_blank'>SynDevRx: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://syndevrx.com/lead-compound-sdx-7320/' target='_blank'>SynDevRx Drug Information Page: Evexomostat (SDX-7320)</a> </li><li class='seamTextUnorderedListItem'><a href='https://syndevrx.com/science/polymer-drug-conjugation/' target='_blank'>SynDevRx: Polymer Drug Conjugates</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/piqray' target='_blank'>Breastcancer.org: Alpelisib (Piqray®)</a> </li></ul>

NEAREST SITE: 383 miles Arrowhead Regional Medical Center Colton,CA

VISITS: About 1 visit a week for 5 to 6 months

NCT ID: NCT03412643

Chemotherapy and HER2-Targeted Therapies Before Surgery for Stage I-III, HER2 Negative Breast Cancer That Shows Other HER2 Activity

An Open-Label Phase II Trial to Evaluate the Efficacy and Safety of Neoadjuvant Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel Plus Trastuzumab and Pertuzumab in Early Stage HER2-Negative Breast Cancer Patients Selected With a Test Measuring Live Cell HER2 Signaling Transduction (FACT 1) Scientific Title

• <p class="seamTextPara"> You will receive the following before surgery over 5-6 months: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Doxorubicin (Adriamycin®) and cyclophosphamide (Cytoxan®), by IV, every 2 or 3 weeks, for 2-3 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">followed by</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV, weekly, for 3 months</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®), by IV, every 3 weeks, for 2 months</li> <li class="seamTextUnorderedListItem">Pertuzumab (Perjeta®), by IV, every 3 weeks, for 2 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">1 biopsy</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®) and pertuzumab (Perjeta®) are targeted therapies commonly used to treat HER2 positive (HER2+) breast cancer. </li> <li class="seamTextUnorderedListItem">They are not approved for use on HER2 negative (HER2-) breast cancer. Their use in this trial is considered experimental. </li> <li class="seamTextUnorderedListItem">The Celcuity CELx HER2 Signaling Function (HSF) test checks breast cancer cells for activity called abnormal HER2 signaling. </li> <li class="seamTextUnorderedListItem">To be eligible for this trial, your cancer cells must test positive for abnormal HER2 signaling.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03412643' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://ww5.komen.org/BreastCancer/TumorCharacteristics.html' target='_blank'>Susan G. Komen: Tumor Characteristics</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted_therapies' target='_blank'>Breastcancer.org: Targeted Therapies</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.ncbi.nlm.nih.gov/pubmed/32036454' target='_blank'>Journal Abstract: New HER2 Negative Breast Cancer Subtype Responsive to Anti-HER2 Therapy Identified</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.oncotarget.com/article/12480/text/' target='_blank'>Journal Article: HER2 Signaling Activity Test</a> </li></ul>

NEAREST SITE: 386 miles Loma Linda University Cancer Center Loma Linda,CA

VISITS: 1-2 visits within 1-2 days

NCT ID: NCT03598426

3 Regimens to Prevent Allergic Reactions to Chemotherapy for Women with Stage I-IV Breast Cancer

Conventional Prophylactic Regimen of Oral Dexamethasone Versus Short-course Intravenous Dexamethasone in Preventing Paclitaxel-related Hypersensitivity Reactions in Breast and Gynecologic Oncology Patients: A Prospective, Randomized, Open-label Study Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 3 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Dexamethasone, by mouth</li> </ul> <p class="seamTextPara"> followed 1 day later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Diphenhydramine (Benadryl®), by IV</li> <li class="seamTextUnorderedListItem">Famotidine, by IV</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Dexamethasone, by IV</li> <li class="seamTextUnorderedListItem">Diphenhydramine (Benadryl®), by IV</li> <li class="seamTextUnorderedListItem">Famotidine, by IV</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Dexamethasone, by mouth</li> </ul> <p class="seamTextPara"> followed 1 day later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Dexamethasone, by IV</li> <li class="seamTextUnorderedListItem">Diphenhydramine (Benadryl®), by IV</li> <li class="seamTextUnorderedListItem">Famotidine, by IV</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®) is a chemotherapy drug.</li> <li class="seamTextUnorderedListItem">Dexamethasone, diphenhydramine (Benadryl®), and famotidine are drugs that help prevent allergic reactions to chemotherapy.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03598426' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/taxol' target='_blank'>Breastcancer.org: Paclitaxel (Taxol®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a687011.html' target='_blank'>MedlinePlus: Famotidine</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a682792.html' target='_blank'>MedlinePlus: Dexamethasone</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a682539.html' target='_blank'>MedlinePlus: Diphenhydramine (Benadryl®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/side_effects/allergic' target='_blank'>Breastcancer.org: Allergic Reactions</a> </li></ul>

NCT ID: NCT03925675

PET/CT for Brain Metastases

Differentiating Brain Tumor Recurrence From Treatment-Induced Necrosis Using 18F-Fluciclovine (Anti-18f-facbc) PET and Multiparametric MR Imaging Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fluciclovine-F18 (Axumin®) 1 time</li> <li class="seamTextUnorderedListItem">PET/CT imaging 1 time</li> <li class="seamTextUnorderedListItem">MRI</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Brain surgery to remove the tumor</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fluciclovine-F18 (Axumin®) is an FDA approved PET imaging agent for biological recurrent prostate cancer.</li> <li class="seamTextUnorderedListItem">A positron emission tomography (PET) scan is an imaging test that uses a radioactive substance called a tracer that can look for and attach to cancer cells.</li> <li class="seamTextUnorderedListItem">A computed tomography (CT) scan produces body pictures created by x-ray energy.</li> <li class="seamTextUnorderedListItem">A magnetic resonance imaging (MRI) scan produces body pictures created by using magnetic energy rather than x-ray energy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03925675' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li></ul>

NEAREST SITE: 421 miles Comprehensive Cancer Centers of Nevada Las Vegas,NV

NCT ID: NCT04389632

SGN-B6A in Advanced Breast Cancer

A Phase 1 Study of SGN-B6A in Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">SGN-B6A, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">SGN-B6A is an investigational therapy. This means it is only available in a clinical trial.</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a cancer therapy that combines an antibody that targets cancer cells with a drug that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">SGN-B6A is an antibody-drug conjugate (ADC) targeting integrin beta-6. </li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of advanced or metastatic cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04389632' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://mbcn.org' target='_blank'>Metastatic Breast Cancer Network</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.biospace.com/article/releases/seattle-genetics-announces-initiation-of-phase-1-clinical-trials-for-two-novel-antibody-based-drug-candidates/' target='_blank'>BioSpace Press Release: Seagen Announces Initiation of Phase 1 Clinical Trials for Two Novel Antibody-Based Drug Candidates</a> </li></ul>

VISITS: 3 visits every month

NCT ID: NCT04931823

CPO-100 Chemotherapy For Advanced Breast Cancer

A Phase 1, Multicenter, Single Agent Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of CPO-100 in Adult Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CPO-100, by IV, weekly, 3 weeks on, 1 week off, ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CPO-100 is a taxane-based chemotherapy being studied in clinical trials.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04931823' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://conjuprobio.com/products/' target='_blank'>Sponsor website: Product and Pipelines</a> </li></ul>

NCT ID: NCT06239467

OKI-219 Targeted Therapy for Advanced HR+ Breast Cancer with PI3K Mutations

PIKture-01: First-in-Human Study of the PI3KÃŽ±H1047R Mutant-Selective Inhibitor OKI-219 as Monotherapy in Participants With Advanced Solid Tumors and in Combination With Endocrine Therapy or HER2-Targeted Therapy in Participants With Advanced Breast Cancer (PIKture-01) Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: HR positive, HER2 negative</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">OKI-219, by mouth, daily</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: HER2 positive</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">OKI-219, by mouth, daily</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®), by IV</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PI3KαH1047R is a common type of PI3KCA mutation.</li> <li class="seamTextUnorderedListItem">OKI-219 is an experimental targeted therapy called a PI3Kα inhibitor. If there is a mutation in the PIK3CA gene, the PI3K pathway can become overactivated which allows cancer cells to grow. OKI-219 may block the PI3K pathway.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a hormone therapy called a selective estrogen receptor degraders (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®) is an anti-HER2 targeted therapy routinely used for HER2+ breast cancer.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06239467' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://onkuretherapeutics.com/pipeline/' target='_blank'>OnKure: OKI-219 Drug Information Page</a> </li></ul>

NEAREST SITE: 446 miles California Protons Cancer Therapy Center San Diego,CA

VISITS: 10 visits

NCT ID: NCT01766297

Proton Radiation Therapy For DCIS and Early-Stage Breast Cancer

Phase II Protocol of Proton Therapy for Partial Breast Irradiation in Early Stage Breast Cancer Scientific Title

• <p class="seamTextPara"> All participants will receive: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Proton Radiotherapy, 10 sessions</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Radiation is used after surgery to kill any cancer cells that may have been left in the breast. </li> <li class="seamTextUnorderedListItem">Proton therapy is a form of external beam radiation that uses protons (instead of x-rays) to treat the tumor. </li> <li class="seamTextUnorderedListItem">Because the proton beam can be more directly targeted to the tumor, proton therapy may result in fewer side effects than x-ray radiation.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT01766297' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://www2.mdanderson.org/cancerwise/2010/03/is-proton-therapy-right-for-you.html' target='_blank'>MD Anderson: Proton therapy</a> </li></ul>

NEAREST SITE: 446 miles Scripps- MD Anderson Cancer San Diego,CA

VISITS: 5 visits per week for 3 or 5 weeks

NCT ID: NCT02912312

The Risk of Developing Lymphedema When Using Hypofractionated Radiation For DCIS & Stage I-III Breast Cancer

Shortening Adjuvant Photon Irradiation to Reduce Edema (SAPHIRE): A Randomized Trial of Hypofractionated Versus Conventionally Fractionated Regional Nodal Irradiation for Invasive Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Shorter radiation schedule (hypofractionated)</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">15 radiation treatments: 5 days a week, for 3 weeks</li> <li class="seamTextUnorderedListItem">Questionnaires, blood draws, and arm measurements, 7 visits over 10.5 years</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard radiation</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">25 radiation treatments: 5 days a week, for 5 weeks</li> <li class="seamTextUnorderedListItem">Questionnaires, blood draws, and arm measurements, 7 visits over 10.5 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Lymphedema is abnormal swelling in the arm, hand, breast, or torso that develops as a side effect of breast cancer treatments like surgery and radiation therapy. </li> <li class="seamTextUnorderedListItem">Giving the traditional amount of radiation in a shorter period of time is called hypofractionated whole-breast radiation.</li> <li class="seamTextUnorderedListItem">The hypofractionated radiation therapy used in this trial takes about 4 weeks.</li> <li class="seamTextUnorderedListItem">The tradiational radiation therapy used in this trial takes about 6 weeks.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02912312' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.breastcancer.org/treatment/lymphedema/how/treat_impact' target='_blank'>Breastcancer.org: Impact of Radiation Therapy on Lymphedema Risk</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.breastcancer.org/research-news/shorter-radiation-better-for-early-stage' target='_blank'>Breastcancer.org: Shorter Radiation for Early Stage Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/lymphedema' target='_blank'>Breastcancer.org: Lymphedema</a> </li></ul>

NEAREST SITE: 446 miles CureScience Institute San Diego,CA

NCT ID: NCT05106725

Registry of Wearable Device Data to Study Brain Metastasis

Study of Clinical Biomarkers in Human Health and Disease (Healthiomics) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Wearable device</li> <li class="seamTextUnorderedListItem">Collection of biological samples: blood, tumor, cerebrospinal fluid, urine</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Wearable devices such as FitBits are used to track your physical activity.</li> <li class="seamTextUnorderedListItem">Cerebrospinal fluid (CSF) is the fluid that surrounds your brain and spinal cord. CSF is typically collected during a procedure called a lumbar puncture, also known as a spinal tap.</li> <li class="seamTextUnorderedListItem">If you do not have cancer or a brain disorder, your data will be compared to data collected by people with brain metastasis.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05106725' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li></ul>

NEAREST SITE: 447 miles Moores Cancer Center San Diego,CA

NCT ID: NCT04343157

Cognitive-Sparing Stereotactic Radiosurgery for Brain Metastasis

UCSD Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases: Avoidance of Eloquent White Matter and Hippocampal Regions Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cognitive-sparing stereotactic radiosurgery</li> <li class="seamTextUnorderedListItem">MRI scans, 4 scans within 6 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cognitive tests</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule.</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiation (stereotactic radiosurgery) delivers high-dose, precisely-targeted radiation in fewer doses than traditional radiation therapy.</li> <li class="seamTextUnorderedListItem">Cognitive-sparing stereotactic radiosurgery is a targeted radiation therapy that avoids the white matter and hippocampus (parts of the brain that control memory, language, attention, and cognition).</li> <li class="seamTextUnorderedListItem">A magnetic resonance imaging (MRI) scan produces body pictures created by using magnetic energy rather than x-ray energy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04343157' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li></ul>

NEAREST SITE: 447 miles University of California San Diego San Diego,CA

NCT ID: NCT05546268

MRT-2359 Targeted Therapy with Hormone Therapy for Advanced HR+, HER2- Breast Cancer

A Phase 1/2 Study of Oral MRT-2359 in Patients With MYC-Driven and Other Selected Solid Tumors Including Lung Cancer and Diffuse B-Cell Lymphoma Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">MRT-2359, by mouth</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">MRT-2359 is an experimental targeted therapy called a molecular glue degrader (MGD). Molecular glue degrader (MGD) may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor degrader (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">This trial is enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05546268' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.monterosatx.com/queen/' target='_blank'>Monte Rosa Therapeutics: MRT-2359 Drug Information Page</a> </li></ul>

NEAREST SITE: 510 miles Pioneers Medical Health District Brawley,CA

NCT ID: NCT05414812

Women's Health and Fertility Support for Women with Stage 0-IV Breast Cancer in Imperial County, California

Intervening on Women's Health for Rural Young Breast Cancer Survivors Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Screen for oncofertility needs</li> <li class="seamTextUnorderedListItem">Receive survivorship care plan (SCP)</li> <li class="seamTextUnorderedListItem">Receive oncofertility navigation, in-person or virtual, 1 time</li> <li class="seamTextUnorderedListItem">Receive oncofertility consultation with reproductive specialist, in-person or virtual, 1 time</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Receive usual care</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Oncofertility involves interventions to help people with cancer preserve their ability to have children (fertility).</li> <li class="seamTextUnorderedListItem">The oncofertility needs screening assesses your desire to have a child in the future, your need for contraception, and your sexual health/menopause symptoms.</li> <li class="seamTextUnorderedListItem">The survivorship care plan (SCP) encompasses content on screening and management strategies for fertility concerns/pregnancy health, contraception, hot flashes, and sexual health.</li> <li class="seamTextUnorderedListItem">The oncofertility navigation will assess your oncofertility needs, review the SCP, and provide support with the goal of engaging in oncofertility care.</li> <li class="seamTextUnorderedListItem">This trial is also available in Spanish.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05414812' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.choc.org/news/5-things-you-should-know-about-oncofertility/' target='_blank'>UC Irvine: Oncofertility</a> </li></ul>

NEAREST SITE: 517 miles Saint Alphonsus Regional Medical Center Boise,ID

NCT ID: NCT03937154

Romiplostim for Low Blood Platelets During Chemotherapy in People with Breast Cancer

A Phase 3 Randomized Placebo-controlled Double-blind Study of Romiplostim for the Treatment of Chemotherapy-induced Thrombocytopenia in Patients Receiving Chemotherapy for Treatment of Non-small Cell Lung Cancer (NSCLC), Ovarian Cancer, or Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Romiplostim (Nplate®), by injection, 3-6 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for romiplostim (Nplate®), by injection, 3-6 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Chemotherapy-induced thrombocytopenia (CIT) is having a low number of blood platelets, which are blood cells that help your blood clot, as a side effect of chemotherapy.</li> <li class="seamTextUnorderedListItem">Romiplostim (Nplate®) increases the number of blood platelets to help your blood clot and reduce your risk of bleeding.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03937154' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a609008.html' target='_blank'>MedlinePlus: Romiplostim (Nplate®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mayoclinic.org/diseases-conditions/thrombocytopenia/symptoms-causes/syc-20378293#:~:text=Thrombocytopenia%20is%20a%20condition%20in,plugs%20in%20blood%20vessel%20injuries.' target='_blank'>Mayo Clinic: Thrombocytopenia</a> </li></ul>

NEAREST SITE: 533 miles OHSU Knight Cancer Institute Portland,OR

VISITS: 3 visits within 6 weeks

NCT ID: NCT03270059

Gadolinium and Ferumoxytol with MRI Scans for Brain Metastasis

The Feasibility of Steady State CBV Mapping Using Ferumoxytol Immediately After Gadolinium Enhanced MRI of the CNS Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Gadolinium, by IV</li> <li class="seamTextUnorderedListItem">Ferumoxytol, by IV</li> <li class="seamTextUnorderedListItem">MRI scans</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">A magnetic resonance imaging (MRI) scan produces body pictures created by using magnetic energy rather than x-ray energy.</li> <li class="seamTextUnorderedListItem">Ferumoxytol and gadolinium can increase the visibility of body structures in imaging such as MRI scans.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03270059' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li><li class='seamTextUnorderedListItem'><a href='https://mriquestions.com/ferumoxytol.html' target='_blank'>MRI Questions: Ferumoxytol</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-gadolinium-based-contrast-agents' target='_blank'>Food and Drug Administration: Gadolinium</a> </li></ul>

VISITS: 2 visits within 1 week, then 2 visits within 2 months

NCT ID: NCT03649880

FMISO PET/CT and PET/MRI Scans for Brain Metastasis

Feasibility of [¹⁸F]-Fluoromisonidazole (FMISO) in Assessment of Malignant Brain Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">FMISO tracer, by IV</li> <li class="seamTextUnorderedListItem">PET/CT scan or PET/MRI scan, 2 scans within 1 week, then 2 scans within 2 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">A positron emission tomography (PET) scan is an imaging test that uses a radioactive substance called a tracer that can look for and attach to cancer cells.</li> <li class="seamTextUnorderedListItem">A computed tomography (CT) scan produces body pictures created by x-ray energy.</li> <li class="seamTextUnorderedListItem">A magnetic resonance imaging (MRI) scan produces body pictures created by using magnetic energy rather than x-ray energy.</li> <li class="seamTextUnorderedListItem">This imaging trial will use a tracer called ¹⁸F-fluoromisonidazole (FMISO).</li> <li class="seamTextUnorderedListItem">FMISO with PET/CT and PET/MRI imaging techniques produce images of the brain that may help investigators see how much oxygen is getting in the brain tumors.</li> <li class="seamTextUnorderedListItem">The imaging techniques will study if brain tumor cells have low oxygen levels, called tumor hypoxia, which helps cancer cells grow.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03649880' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li></ul>

VISITS: Monthly visits for 1 year

NCT ID: NCT03801369

Olaparib and Durvalumab in Metastatic Triple Negative & ER Low Breast Cancer

A Phase II, Open Label, Study of Olaparib and Durvalumab (MEDI4736) in Patients With Metastatic Triple Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Olaparib (Lynparza®), by mouth, twice daily for 1 month, then once a month for 1 year</li> <li class="seamTextUnorderedListItem">Durvalumab (Imfinzi®), by IV, monthly, for 1 year</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional procedures:</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">2-3 tumor biopsies</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Breast cancer that tests positive for 1%-10% estrogen receptors is called ER Low.</li> <li class="seamTextUnorderedListItem">This trial is enrolling people with triple negative as well as ER Low breast cancer.</li> <li class="seamTextUnorderedListItem">Lynparza is a PARP inhibitor. It stops the growth of cancer cells by blocking enzymes called poly ADP ribose polymerase (PARP). </li> <li class="seamTextUnorderedListItem">It is approved to treat certain types of ovarian cancer. </li> <li class="seamTextUnorderedListItem">Imfinzi is a type of immunotherapy drug called a PD-L1 inhibitor. It gets the body's immune system to go after cancer cells. </li> <li class="seamTextUnorderedListItem">It is approved to treat certain types of lung cancer. </li> <li class="seamTextUnorderedListItem">Preclinical studies suggest this drug combination may be effective in patients with metastatic triple negative breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03801369' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.imfinzi.com/stage-3-nsclc/about/how-imfinzi-works.html?source=imz_c_c_45&umedium=cpc&uadpub=google&ucampaign=2018imfinzidtcnsclcbranded_general&ucreative=branded_alone_ex&uplace=durvalumab&outcome=dtc&cmpid=1' target='_blank'>Durvalumab (Imfinzi®) Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.lynparza.com/ovarian-cancer/recurrent-ovarian-cancer.html?source=lyn_d_c_2&umedium=cpc&uadpub=google&ucampaign=lynparzadtcbranded_alone_2019&ucreative=branded_alone_ex&uplace=olapariblynparza&outcome=dtc&cmpid=1' target='_blank'>Olaparib (Lynparza®) Drug Information Page</a> </li></ul>

VISITS: At least 4 visits within 1 year

NCT ID: NCT04993313

Verbal Counseling and Photo Guide to Reduce Stress from Radiation Therapy for Stage 0-III Breast Cancer

A Randomized Trial of Standard Verbal Counseling With or Without a Pictorial Educational Tool to Reduce Psychological Morbidity in Women Receiving Breast Radiation Therapy Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Complete verbal counseling</li> <li class="seamTextUnorderedListItem">View a photo guide</li> <li class="seamTextUnorderedListItem">Questionnaires, 4 times</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Control</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Complete verbal counseling</li> <li class="seamTextUnorderedListItem">Questionnaires, 4 times</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Radiation therapy uses high-energy x-rays to damage cancer cell DNA. These x-rays stop cancer cells from dividing and growing, thus slowing or stopping tumor growth.</li> <li class="seamTextUnorderedListItem">Starting radiation therapy for breast cancer can be stressful. </li> <li class="seamTextUnorderedListItem">Education about what to expect may reduce stress, anxiety, and depression in people starting radiation therapy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04993313' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/radiation-therapy' target='_blank'>Breastcancer.org: Radiation</a> </li></ul>

NEAREST SITE: 533 miles Site 9280 Portland,OR

NCT ID: NCT05565417

IMT-009 Targeted Therapy for Advanced Triple Negative Breast Cancer with a CD161 or CLEC2D Mutation

A Phase 1/2a, First-in-Human (FIH), Open-Label, Dose-Escalation and Dose Expansion Study of the Monoclonal Antibody IMT-009 in Patients With Advanced Solid Tumors or Lymphomas Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">IMT-009, by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">IMT-009 is an experimental targeted therapy called a CD161 inhibitor. Blocking CD161 may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: CD161, CLEC2D</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05565417' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.healio.com/news/hematology-oncology/20220922/fda-clears-ind-application-for-cancer-therapeutic-imt009' target='_blank'>Healio: IMT-009</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.prnewswire.com/news-releases/immunitas-therapeutics-receives-fda-clearance-of-ind-application-for-imt-009-in-solid-tumors-and-hematological-malignancies-301628999.html' target='_blank'>Immunitas Therapeutics Press Release: IMT-009</a> </li></ul>

VISITS: 4 visits

NCT ID: NCT05704062

MRI Scans to Predict and Evaluate Response to Chemotherapy Before Surgery for People with Stage I-III Breast Cancer

Multi-Functional Magnetic Resonance Imaging Modalities for Assessment of Breast Cancer Response to Neoadjuvant Chemotherapy Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">MRI scans, 4 times over the course of chemotherapy</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Neoadjuvant therapy is when you receive treatment, like chemotherapy, before surgery. Doctors use it to shrink tumors and to see how your cancer responds to the given therapies. </li> <li class="seamTextUnorderedListItem">A magnetic resonance imaging (MRI) scan is a type of scan that uses a very strong magnet and no radiation or x-ray energy to take very detailed pictures of parts of the body.</li> <li class="seamTextUnorderedListItem">MRI scans are often used as standard of care to take pictures of breast tumor(s) before and after chemotherapy treatment to measure the tumor size changes in response to treatment and plan for surgery.</li> <li class="seamTextUnorderedListItem">MRI scans are used because the images it takes are very clear and the borders of the tumor can be measured very accurately. However the tumor size alone is often not a good early indicator of whether or not the tumor responds to treatment.</li> <li class="seamTextUnorderedListItem">You will receive 4 MRI scans: before treatment, after the first treatment cycle, midway through treatment, and at the end of treatment.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05704062' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/screening-testing/breast-mri' target='_blank'>Breastcancer.org: Breast MRI</a> </li></ul>

NEAREST SITE: 538 miles Providence Portland Medical Center Portland,OR

NCT ID: NCT05323955

Adding Tucatinib Targeted Therapy to Standard of Care Therapy for Metastatic HER2+ Breast Cancer with Brain Metastases

Secondary BRain Metastases Prevention After Isolated Intracranial Progression on Trastuzumab/Pertuzumab or T-DM1 in Patients With aDvanced Human Epidermal Growth Factor Receptor 2+ brEast Cancer With the Addition of Tucatinib (BRIDGET) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Continue standard of care trastuzumab (Herceptin®), pertuzumab (Perjeta®), or trastuzumab emtansine (Kadcyla®, T-DM1)</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®), by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab emtansine (Kadcyla®, T-DM1) is an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An ADC is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Trastuzumab emtansine (Kadcyla®, T-DM1)'s antibody targets HER2 and delivers an anti-cancer drug called emtansine.</li> <li class="seamTextUnorderedListItem">Pertuzumab (Perjeta®) and trastuzumab (Herceptin®) are anti-HER2 targeted therapies used to treat HER2+ breast cancer.</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®) is a type of targeted therapy called a tyrosine kinase inhibitor. It blocks an enzyme that helps cancer cells grow.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05323955' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/featured-clinical-trials/#toggle-id-1' target='_blank'>MBCBrainMets.org: BRIDGET Trial Video with Dr. Sarah Sammons</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/herceptin' target='_blank'>Breastcancer.org: Trastuzumab (Herceptin®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/kadcyla' target='_blank'>Breastcancer.org: Trastuzumab Emtansine (Kadcyla®, T-DM1)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/perjeta' target='_blank'>Breastcancer.org: Pertuzumab (Perjeta®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/tukysa' target='_blank'>Breastcancer.org: Tucatinib (Tukysa®)</a> </li></ul>

NCT ID: NCT05467891

Targeted Therapy and Hormone Therapy for Stage I-III HR+, HER2- Breast Cancer That Has Recurred Locally

A Phase II Study of Ribociclib And Endocrine Treatment of Physician's Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®), by mouth, daily, 3 weeks on, 1 week off for 3 years</li> <li class="seamTextUnorderedListItem">Physician's choice of hormone therapy: Fulvestrant (Faslodex®), by injection, 2 times in 1 month then monthly for 5 years, or anastrozole (Arimidex®), letrozole (Femara®), or exemestane (Aromasin®), by mouth, daily for 5 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®) is a type of targeted therapy called a CDK 4/6 inhibitor. CDK 4/6 inhibitors block two enzymes, CDK4 and CDK6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor downregulator (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®) are types of hormone therapy called aromatase inhibitors. They are commonly used to treat hormone receptor positive breast cancer.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women will also be given a drug that will put women in temporary menopause.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+ or 2+.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05467891' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/kisqali' target='_blank'>Breastcancer.org: Ribociclib (Kisqali®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/arimidex' target='_blank'>Breastcancer.org: Anastrozole (Arimidex®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/femara' target='_blank'>Breastcancer.org: Letrozole (Femara®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/aromasin' target='_blank'>Breastcancer.org: Exemestane (Aromasin®)</a> </li></ul>

NEAREST SITE: 544 miles Site 04 Vancouver,WA

NCT ID: NCT05654532

AC699 Hormone Therapy for Advanced ER+, HER2- Breast Cancer

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of AC699 in Patients With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Locally Advanced or Metastatic Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">AC699, by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">AC699 is an experimental hormone therapy called a selective estrogen receptor degrader (SERD). SERDs bind to and break down estrogen receptors.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05654532' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/oral-serds/' target='_blank'>Metastatic Trial Talk: Update on Oral SERDs for Estrogen Receptor-Positive MBC</a> </li></ul>

NEAREST SITE: 595 miles South Texas Accelerated Research Therapeutics Mountain Region West Valley City,UT

NCT ID: NCT05194072

SGN-B7H4V for Advanced HER2 Negative Breast Cancer

A Phase 1 Study of SGN-B7H4V in Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">SGN-B7H4V, by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule.</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">SGN-B7H4V is an experimental antibody-drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a chemotherapy that kills cancer cells.</li> <li class="seamTextUnorderedListItem">The antibody in this drug targets B7-H4 proteins and delivers the chemotherapy MMAE.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">This study is also enrolling patients with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05194072' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Antibody-Drug Conjugates (ADCs)</a> </li><li class='seamTextUnorderedListItem'><a href='https://investor.seagen.com/press-releases/news-details/2021/Seagen-to-Highlight-Two-Novel-Antibody-Drug-Conjugates-ADCs-at-the-SITC-36th-Annual-Meeting/default.aspx' target='_blank'>Seagen Press Release: SGN-B7H4V</a> </li><li class='seamTextUnorderedListItem'><a href='https://jitc.bmj.com/content/9/Suppl_2/A895' target='_blank'>Journal Article: SGN-B7H4V</a> </li></ul>

NEAREST SITE: 595 miles START - Mountain Region West Valley City,UT

NCT ID: NCT05251714

CFI-402257 Targeted Therapy with Hormone Therapy in Breast Cancer

A Dose-confirming Study of CFI-402257 as a Single Agent in Advanced Solid Tumors and in Combination With Fulvestrant in Patients With ER+/HER2- Advanced Breast Cancer After Disease Progression on Prior CDK4/6 and Endocrine Therapy Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CFI-402257, by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CFI-402257, by mouth, daily</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection, every 2 weeks for 1 month, then weekly</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CFI-402257 is an experimental targeted therapy called a TTF inhibitor. Blocking TTF may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of anti-estrogen therapy called a SERD (selective estrogen receptor degrader). SERDs work by binding to and breaking down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women and men in Group 2 will also be given a drug that will put women in temporary menopause.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05251714' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://treadwelltx.com/pipeline/' target='_blank'>Treadwell Therapeutics Drug Information Page: CFI-402257</a> </li><li class='seamTextUnorderedListItem'><a href='https://treadwelltx.com/science/' target='_blank'>Treadwell Therapeutics: TTK Inhibitor</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li></ul>

NEAREST SITE: 595 miles South Texas Accelerated Research Therapeutics | START Rocky Mountain Region West Valley City,UT

VISITS: 5 visits within 1 week, then 1-3 visits per month

NCT ID: NCT05537740

BAY3375968 Immunotherapy with PD-1 Inhibitor for Advanced Triple Negative Breast Cancer

First-in-human Dose-escalation and Expansion Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of the Anti-CCR8 Antibody BAY 3375968 as Monotherapy and in Combination With Pembrolizumab in Participants With Selected Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BAY3375968, by IV</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®), by IV</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BAY3375968 is an experimental immunotherapy called a CCR8 inhibitor. mBAY3375968 binds to CCR8 on immune cells which allows the immune system to fight cancer cells.</li> <li class="seamTextUnorderedListItem">Pembrolizumab (Keytruda®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05537740' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy/keytruda' target='_blank'>Abstract: BAY3375968</a> </li><li class='seamTextUnorderedListItem'><a href='https://aacrjournals.org/cancerres/article/82/12_Supplement/2866/704369' target='_blank'>Breastcancer.org: Pembrolizumab (Keytruda®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/immune-checkpoint-inhibitor/' target='_blank'>Metastatic Trial Talk: Update on Immunotherapy for MBC: Immune Checkpoint Inhibitors</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy' target='_blank'>Breastcancer.org: Immunotherapy</a> </li></ul>

NEAREST SITE: 595 miles START Mountain Region West Valley City,UT

NCT ID: NCT05864144

SNS-101 With or Without Cemiplimab for Advanced Breast Cancer

A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SNS-101 (Anti VISTA) as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">SNS-101, by IV, every 3 weeks</li> </ul> <p class="seamTextPara"> with or without: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cemiplimab, by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">SNS-101 is an anti-VISTA IgG1 monoclonal antibody. SNS-101 is an immune checkpoint inhibitor that may help other immunotherapies work better.</li> <li class="seamTextUnorderedListItem">Cemiplimab (Libtayo®) is a type of immunotherapy called an immune checkpoint inhibitor. It gets the immune system to go after cancer cells by blocking the protein PD-1. Cemiplimab is approved by the FDA for other cancers but it considered experimental for breast cancer.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of advanced cancers.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05864144' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.senseibio.com/wp-content/uploads/2022/05/SITC2022.pdf' target='_blank'>Sensei Biotherapeutics research poster: SNS-101</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/about-cancer/treatment/drugs/cemiplimab-rwlc' target='_blank'>National Cancer Institute: Cemiplimab</a> </li></ul>

NCT ID: NCT06206837

Vepdegestrant Hormone Therapy with PF-07220060 CDK4 Inhibitor for Advanced ER+ or ER Low, HER2- Breast Cancer

AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF VEPDEGESTRANT (ARV-471/PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH PF-07220060 IN PARTICIPANTS AGED 18 YEARS AND OLDER WITH ER+/HER2- ADVANCED OR METASTATIC BREAST CANCER Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Vepdegestrant (ARV-471), by mouth, daily</li> <li class="seamTextUnorderedListItem">PF-07220060, by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Vepdegestrant (ARV-471) is an experimental hormone therapy called a PROTAC protein degrader that breaks down estrogen receptors.</li> <li class="seamTextUnorderedListItem">PF-07220060 is an experimental targeted therapy called a CDK4 inhibitor. CDK4 is a protein that helps cancer grow. Blocking CDK4 helps slow or stop cancer cells from growing.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06206837' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.pfizerclinicaltrials.com/find-a-trial/nct06206837-breast-cancer-trial' target='_blank'>Pfizer: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.arvinas.com/pipeline-programs/estrogen-receptor' target='_blank'>Arvinas Estrogen Receptor: ARV-471 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://cdn.pfizer.com/pfizercom/product-pipeline/Pipeline_Update_04MAY2021.pdf?VersionId=.06Q_HtLdkBW8lme0Y3EXpraBpgGspyg' target='_blank'>Pfizer: PF-07220060 Drug Information Page</a> </li></ul>

NCT ID: NCT06253130

IMP1734 PARP Inhibitor for Advanced Breast Cancer

A First-in-human, Phase 1/2, Open-label, Multi-center, Dose-escalation, Dose-optimization, and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of PARP1 Selective Inhibitor, IMP1734, as Monotherapy in Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">IMP1734, by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">IMP1734 is an experimental targeted therapy called a PARP inhibitor. PARP inhibitors work by blocking the action of poly (ADP-ribose) polymerase, an enzyme that helps repair DNA.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06253130' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.eikontx.com/#pipeline' target='_blank'>Eikon Therapeutics: IMP1734/EIK1003 Drug Information Page</a> </li></ul>

NCT ID: NCT06400472

LY4170156 ADC for Advanced Triple Negative Breast Cancer

A First-in-Human, Phase 1a/1b Trial to Assess the Safety, Tolerability and Preliminary Efficacy of LY4170156, an Antibody-Drug Conjugate Targeting Folate Receptor α-Expressing Tumor Cells, in Participants With Selected Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LY4170156, by IV</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LY4170156 is an experimental targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">The antibody in LY4170156 targets folate receptor alpha and delivers a chemotherapy drug.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06400472' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://trials.lilly.com/en-US/trial/482318' target='_blank'>Eli Lilly and Company: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/?_gl=1*msj5sm*_ga*NDI3ODYxOTY5LjE2NzE2MzcwODA.*_ga_Y9F235S3X2*MTcxMDc3NDgwNy40MTEuMS4xNzEwNzc2MTM5LjQ2LjAuMA..' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li></ul>

NEAREST SITE: 601 miles START Mountain Salt Lake City,UT

NCT ID: NCT06334432

NUV-1511 Targeted Therapy for Advanced Breast Cancer

A Phase 1/2, First-in-Human, Safety and Efficacy Study of NUV-1511 in Adult Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NUV-1511</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">NUV-1511 is an experimental type of targeted therapy called a drug-drug conjugate (DDC).</li> <li class="seamTextUnorderedListItem">A drug-drug conjugate (DDC) targets cancer cells and contains a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06334432' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.nuvationbio.com/pipeline/' target='_blank'>Nuvation Bio: NUV-1511 Drug Information Page</a> </li></ul>

NEAREST SITE: 602 miles Huntsman Cancer Institute Salt Lake City,UT

VISITS: At least 1 visit

NCT ID: NCT02390518

Stereotactic Radiosurgery Dose Escalation for Brain Metastases

Phase I Study of Stereotactic Radiosurgery Dose Escalation for Brain Metastases Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiation to brain metastases</li> <li class="seamTextUnorderedListItem">One metastatic site will receive the experimental dose</li> <li class="seamTextUnorderedListItem">Other sites will receive standard doses</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiation (stereotactic radiosurgery) delivers high-dose, precisely-targeted radiation in fewer doses than traditional radiation therapy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02390518' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mbcalliance.org/marina-kaplan-project' target='_blank'>The Marina Kaplan Project: Breast Cancer Brain Metastases Initiative</a> </li></ul>

NCT ID: NCT02694809

Duavee Hormone Therapy for Postmenopausal Women with DCIS

A Large-scale Multicenter Phase II Study Evaluating the Protective Effect of a Tissue Selective Estrogen Complex (TSEC) in Women With Newly Diagnosed Ductal Carcinoma in Situ Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Conjugated estrogens/bazedoxifene (Duavee®), by mouth, daily for 1 month</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for conjugated estrogens/bazedoxifene (Duavee®), by mouth, daily for 1 month</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Conjugated estrogens/bazedoxifene (Duavee®) is a FDA approved hormone therapy used to treat symptoms of menopause such as hot flashes in women that do not have breast cancer.</li> <li class="seamTextUnorderedListItem">Because conjugated estrogens/bazedoxifene (Duavee®) is not approved in women with DCIS, its use in this study is experimental. </li> <li class="seamTextUnorderedListItem">Margins are the area around where DCIS was removed during surgery. A positive margin means DCIS cells were found in the margin after surgery.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02694809' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mayoclinic.org/drugs-supplements/conjugated-estrogens-and-bazedoxifene-oral-route/description/drg-20061326' target='_blank'>Mayo Clinic: Conjugated Estrogens/Bazedoxifene (Duavee®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/types/ductal-carcinoma-in-situ' target='_blank'>Breastcancer.org: DCIS</a> </li></ul>

NEAREST SITE: 602 miles University of Utah - Huntsman Cancer Institute Salt Lake City,UT

NCT ID: NCT03504488

AB-ROR2-ADC for Advanced Breast Cancer

A Phase 1/2 Dose Escalation and Dose Expansion Study of BA3021 in Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CAB-ROR2-ADC (BA3021) </li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule.</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CAB-ROR2-ADC is a type of drug called an antibody-drug conjugate (ADC). </li> <li class="seamTextUnorderedListItem">This means it uses an antibody that targets cancer cells to deliver a chemotherapy directly to these cells. </li> <li class="seamTextUnorderedListItem">The antibody in this drug targets ROR2 proteins. </li> <li class="seamTextUnorderedListItem">This study is also enrolling patients with other types of advanced cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03504488' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/794991' target='_blank'>NCI Drug Dictionary: CAB-ROR2-ADC</a> </li><li class='seamTextUnorderedListItem'><a href='http://cancerres.aacrjournals.org/content/78/13_Supplement/833' target='_blank'>Cancer Research: Anti-tumor efficacy of BA3021</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.hematologyandoncology.net/archives/april-2017/antibody-drug-conjugates-in-breast-cancer/' target='_blank'>Clinical Advances in Hematology & Oncology: ADC in Breast Cancer</a> </li></ul>

NCT ID: NCT04252859

Using a PET/CT Scan to Find Lobular Breast Cancer Cells Before Surgery for Stage I-IV Lobular Breast Cancer

[18F]Fluoroestradiol-PET/CT Imaging of Invasive Lobular Carcinoma Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PET/CT scan using (18F) FES tracer, 1 time</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">A positron emission tomography (PET) scan is an imaging test that uses a radioactive substance called a tracer. A tracer looks for and attaches to cancer cells.</li> <li class="seamTextUnorderedListItem">Lobular breast cancer is a subtype of breast cancer. It is estimated that 10 to 15 percent of all breast cancers are lobular. </li> <li class="seamTextUnorderedListItem">Standard of care PET/CT scans that use a FDG tracer generally do not find lobular breast cancer tumors as well as they find ductal breast cancer tumors and PET/CT scans are not usually given to people with stage I-II lobular breast cancer. </li> <li class="seamTextUnorderedListItem">This imaging trial will use a tracer called (18F)Fluoroestradiol (FES). Researchers believe this tracer is better at locating and attaching to lobular cancer cells than the standard of care tracer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04252859' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://lobularbreastcancer.org/imagingilc/' target='_blank'>Lobular Breast Cancer Alliance: Imaging and Lobular Breast Cancer</a> </li></ul>

VISITS: 5 visits a month, ongoing

NCT ID: NCT04315233

Ribociclib and Belinostat for Advanced Triple Negative Breast Cancer

A Phase I/Ib Trial of the CDK4/6 Antagonist Ribociclib And The HDAC Inhibitor Belinostat In Patients With Metastatic Triple Negative Breast Cancer And Recurrent Ovarian Cancer With Response Prediction By Genomics (CHARGE) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®), by mouth, daily (3 weeks on, 1 week off), ongoing</li> <li class="seamTextUnorderedListItem">Belinostat (Beleodaq®), by IV, 5 days in a row (1 week on, 3 weeks off), ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Ribociclib (Kisqali®) is a type of targeted therapy called a CDK 4/6 inhibitor--it blocks two enzymes, CDK4 and CDK6, that help cancer cells grow.</li> <li class="seamTextUnorderedListItem">Ribociclib is approved for use in combination with an aromatase inhibitor to treat postmenopausal women with advanced hormone positive, HER2 negative breast cancer--but its use in this trial is considered experimental. </li> <li class="seamTextUnorderedListItem">Belinostat (Beleodaq®) is a type of chemotherapy called an histone deacetylase (HDAC) inhibitor. It is approved for use in some other types of cancer, but its use in breast cancer is considered experimental. </li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of advanced cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04315233' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://chemocare.com/chemotherapy/drug-info/belinostat.aspx' target='_blank'>Chemocare.com: Belinostat (Beleodaq®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a617008.html' target='_blank'>MedLinePlus: Ribociclib (Kisqali®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.onclive.com/view/cdk4-6-inhibitors-make-headway-in-her2-and-triple-negative-breast-cancers' target='_blank'>OncLive: CDK4/6 Inhibitors Make Headway in HER2+ and Triple-Negative Breast Cancers</a> </li></ul>

NEAREST SITE: 602 miles Huntsman Cancer Institute at University of Utah Salt Lake City,UT

NCT ID: NCT04450706

Biopsy to Select Treatment for Metastatic HER2-Negative Breast Cancer

FORESEE: Functional Precision Oncology for Metastatic Breast Cancer: a Feasibility Trial Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Biopsy to collect tumor tissue</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Tumor tissue collected during the biopsy will be used for genomic testing and drug screening.</li> <li class="seamTextUnorderedListItem">Genomic testing identifies DNA in your tumor cells.</li> <li class="seamTextUnorderedListItem">Drug screening tests the response of your tumor cells to potential treatments.</li> <li class="seamTextUnorderedListItem">The results from the genomic testing and drug screening may be used by your doctor to choose your next treatment(s).</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04450706' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancercenter.com/treatment-options/precision-medicine/advanced-genomic-testing' target='_blank'>Cancer Treatment Centers of America: Genomic Testing</a> </li></ul>

NCT ID: NCT05291507

Heat Treatment Before Surgery for Women with Stage I-III Breast Cancer

A Feasibility Evaluation of the Muse Magnetic Resonance Guided Focused Ultrasound System Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Heat treatment of half of tumor with Muse MRgFUS system</li> </ul> <p class="seamTextPara"> followed 2-3 weeks later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Surgery to remove tumor</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The Muse MRgFUS System applies focused ultrasound (FUS) waves to a tumor, which ablates (heats) the tumor tissue to kill cancer cells.</li> <li class="seamTextUnorderedListItem">Only half of your tumor will be ablated before surgery to ensure that no information about you tumor is lost that would impact your care. Because current care often includes testing the tumor, retaining a portion of viable tumor before surgery is advised by the clinical team.</li> <li class="seamTextUnorderedListItem">Neoadjuvant therapy is when you receive treatment before surgery. Doctors use it to shrink tumors and to see how your cancer responds to the given therapies.</li> <li class="seamTextUnorderedListItem">A lumpectomy is sometimes called a partial mastectomy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05291507' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2022-04667&loc=0&ni=10&pn=357&rl=1' target='_blank'>National Cancer Institute: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.hopkinsmedicine.org/interventional-radiology/procedures/tumor/' target='_blank'>Johns Hopkins: Tumor Ablation (Heat Treatment)</a> </li></ul>

NCT ID: NCT05464082

Predict, Prevent, and Treat Early Metastatic Recurrence of HR Low, HER2-/HER2 Low or Triple Negative Breast Cancer

Towards Functional Precision Oncology to Predict, Prevent, and Treat Early Metastatic Recurrence of Triple Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will provide the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Tumor samples</li> <li class="seamTextUnorderedListItem">Blood tests</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Precision oncology is treatment based on specific information from your tumor.</li> <li class="seamTextUnorderedListItem">The tumor samples will be used to complete tests to determine which treatments may be most effective.</li> <li class="seamTextUnorderedListItem">If your cancer comes back (recurrence) after surgery and chemotherapy, your doctor will receive information to help make treatment decisions.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+ or 2+ and ISH-.</li> <li class="seamTextUnorderedListItem">In this trial, hormone receptor (HR) low is defined as 1-10% of cells that are ER+ and PR+.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05464082' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mayoclinic.org/tests-procedures/precision-medicine-breast-cancer/about/pac-20385240' target='_blank'>Mayo Clinic: What is Precision Oncology?</a> </li></ul>

NEAREST SITE: 602 miles University of Utah Huntsman Cancer Institute Salt Lake City,UT

NCT ID: NCT05490472

JAB-2485 Targeted Therapy for Advanced ER+, Triple Negative, or ARID1A Mutated Breast Cancer

A Phase 1/2a, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-2485 in Adult Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">JAB-2485, by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">JAB-2485 is an experimental targeted therapy called an Aurora A inhibitor. Aurora A inhibitors may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: ARID1A</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05490472' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/aurora-a-kinase-inhibitor-jab-2485' target='_blank'>National Cancer Institute: JAB-2485</a> </li></ul>

NEAREST SITE: 602 miles University of Utah Salt Lake City,UT

VISITS: At least 1 visit every 3 weeks

NCT ID: NCT05765851

DS-1103a Targeted Therapy with ADC for Advanced HER2 Low Breast Cancer

A Phase 1, 2-Part, Multicenter, First-In-Human Dose-Escalation and Dose-Expansion Study of DS-1103a Combination Therapy in Subjects With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DS-1103a, by IV</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (Enhertu®), by IV, every 3 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">DS-1103a is an experimental targeted therapy called a SIRPa inhibitor. Inhibiting SIRPa may stimulate the immune system to go after and kill cancer cells.</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (Enhertu®) is an antibody-drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Trastuzumab deruxtecan (Enhertu®)'s antibody targets HER2, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called deruxtecan.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+ or 2+/ISH-.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05765851' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.daiichisankyo.com/rd/pipeline/' target='_blank'>Daiichi Sankyo: Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/enhertu' target='_blank'>Breastcancer.org: Trastuzumab Deruxtecan (Enhertu®)</a> </li></ul>

NEAREST SITE: 602 miles Huntsman Cancer Institute at the University of Utah Salt Lake City,UT

VISITS: 2 visits in 1 month

NCT ID: NCT05821244

Exercise During Chemotherapy for Women with Stage I-III Breast Cancer

Feasibility of Manipulating Exercise Timing in Breast Cancer Survivors on Chemotherapy Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Morning Exercise</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Virtual exercise program between 5-10am, 2 times every week for 1 month</li> <li class="seamTextUnorderedListItem">Aerobic exercise, 1.5 hours every week for 1 month</li> <li class="seamTextUnorderedListItem">Physical tests, 2 times</li> <li class="seamTextUnorderedListItem">Exercise logs</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Evening Exercise</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Virtual exercise program between 3-8am, 2 times every week for 1 month</li> <li class="seamTextUnorderedListItem">Aerobic exercise, 1.5 hours every week for 1 month</li> <li class="seamTextUnorderedListItem">Physical tests, 2 times</li> <li class="seamTextUnorderedListItem">Exercise logs</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The exercise sessions will be virtually supervised by a Cancer Exercise Specialist via telehealth.</li> <li class="seamTextUnorderedListItem">Aerobic exercise refers to cardiovascular exercise, which includes activities such as walking, running, biking, and swimming.</li> <li class="seamTextUnorderedListItem">You may choose the type and location of aerobic exercise.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05821244' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/managing-life/exercise' target='_blank'>Breastcancer.org: Exercise</a> </li></ul>

VISITS: Coincides with radiation sessions, for 2 months

NCT ID: NCT06165653

Guided Meditation During Radiation for People with Brain Metastases

An Interventional Trial Using Guided Meditation During Radiation Therapy for Brain Tumors (Med-RT) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Guided meditation during radiation sessions, 2 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Usual care</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The guided meditation practice involves a series of 5 audio recordings with the following topics: body scan, mindful breathing, mindfulness of discomfort, savoring memories, and loving-kindness.</li> <li class="seamTextUnorderedListItem">Each audio recording is 5 minutes.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06165653' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li></ul>

NEAREST SITE: 602 miles University of Utah Health Hospitals/Huntsman Cancer Institute Population Sciences Salt Lake City,UT

NCT ID: NCT06305312

Referral for Assistance with Basic Needs After an Abnormal Mammogram

Community Services Navigation to Advance Health Equity in Breast Cancer Screening (B-SINCERE) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Referral to United Way of Salt Lake's community referral services (SINCERE)</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Usual Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Standard referral to community resources</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Women with greater need for food, housing, utilities, and transportation are about half as likely to follow up after an abnormal mammogram than women without such needs.</li> <li class="seamTextUnorderedListItem">This trial is studying the United Way of Salt Lake's community referral services (SINCERE) intervention, which connects people to assistance with these needs.</li> <li class="seamTextUnorderedListItem">This trial is also available in Spanish.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06305312' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 602 miles START Center for Cancer Care - Mountain Region Salt Lake City,UT

NCT ID: NCT06395519

ETX-19477 PARG Inhibitor for Advanced Breast Cancer

A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies (ERADIC8) Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ETX-19477, by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ETX-19477 is experimental targeted therapy called a PARG (poly ADP ribose glycohydrolase) inhibitor.</li> <li class="seamTextUnorderedListItem">Blocking PARG may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06395519' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://8five8tx.com/pipeline' target='_blank'>858 Therapeutics: ETX-19477 Drug Information Page</a> </li></ul>

NEAREST SITE: 650 miles Mayo Clinic Arizona Phoenix,AZ

NCT ID: NCT05607004

Z-Endoxifen Hormone Therapy for Premenopausal Women With Stage II ER+, HER2- Breast Cancer

A Randomized Phase 2 Non-inferiority Trial of (Z)-Endoxifen and Exemestane + Goserelin as Neoadjuvant Treatment in Premenopausal Women With ER+/HER2- Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Z-endoxifen, by mouth, daily for 1-7 months</li> </ul> <p class="seamTextPara"> followed by (optional, if low Ki-67 levels after 1 month): </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Z-endoxifen, by mouth, daily for 1-7 months</li> <li class="seamTextUnorderedListItem">Goserelin (Zoladex®), by injection, monthly for 1-7 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Exemestane (Aromasin®), by mouth, daily for 1-7 months</li> <li class="seamTextUnorderedListItem">Goserelin (Zoladex®), by injection, monthly for 1-7 months</li> </ul> <p class="seamTextPara"> followed by (optional, if low Ki-67 levels after 1 month): </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Z-endoxifen, by mouth, daily for 1-7 months</li> <li class="seamTextUnorderedListItem">Goserelin (Zoladex®), by injection, monthly for 1-7 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Z-endoxifen is an experimental hormone therapy called a selective estrogen receptor modulator (SERM). SERMs work by blocking the activity of estrogen that helps cancer cells grow.</li> <li class="seamTextUnorderedListItem">Exemestane (Aromasin®) is a type of hormone therapy called an aromatase inhibitor.</li> <li class="seamTextUnorderedListItem">Goserelin (Zoladex®) is a type of hormone therapy called a LHRH agonist that will put you in temporary menopause.</li> <li class="seamTextUnorderedListItem">Aromatase inhibitors and LHRH agonists block some production of estrogen that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Your type of treatment and length of treatment will be determined by the Ki-67 levels in your tumor after 1 month of treatment.</li> <li class="seamTextUnorderedListItem">Ki-67 is a cancer marker that indicates how well the treatments work to slow cancer cell growth.</li> <li class="seamTextUnorderedListItem">Neoadjuvant therapy is when you receive treatment before surgery. Doctors use it to shrink tumors and to see how your cancer responds to the given therapies.</li> <li class="seamTextUnorderedListItem">Targets or mutations: Ki-67</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05607004' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-drug/def/endoxifen-hydrochloride' target='_blank'>National Cancer Institute: Z-Endoxifen</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/aromasin' target='_blank'>Breastcancer.org: Exemestane (Aromasin®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/zoladex' target='_blank'>Breastcancer.org: Goserelin (Zoladex®)</a> </li></ul>

NEAREST SITE: 650 miles Mayo Clinic Hospital Arizona Phoenix,AZ

VISITS: 1 visit every 3 months

NCT ID: NCT05721248

Safely Stopping Anti-HER2 Targeted Therapy for People with Advanced HER2+ Breast Cancer Who Are Exceptional Responders

The STOP-HER2 Trial: A Phase 2 Study of Stopping Trastuzumab - Outcomes in Patients With HER2+ Metastatic Breast Cancer Scientific Title

• <p class="seamTextPara"> You can choose to participate in 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Choose to Continue Anti-HER2 Treatment</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Continue anti-HER2 treatment</li> <li class="seamTextUnorderedListItem">Visits, monthly for 2-3 months, then every 3 months</li> <li class="seamTextUnorderedListItem">Imaging scans, every 3 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Choose to Stop Anti-HER2 Treatment</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stop anti-HER2 treatment</li> <li class="seamTextUnorderedListItem">Visits, monthly for 2-3 months, then every 3 months</li> <li class="seamTextUnorderedListItem">Imaging scans, every 3 months</li> </ul> <p class="seamTextPara"> followed 1 year later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stop treatment indefinitely if no progression</li> <li class="seamTextUnorderedListItem">Imaging scans (surveillance), every 3-6 months for 10 years</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">You can choose which group you would like to participate in.</li> <li class="seamTextUnorderedListItem">Exceptional response is considered cancer progression being controlled for 3 years or more since starting anti-HER2 targeted treatment.</li> <li class="seamTextUnorderedListItem">This study is also studying whether blood samples that may contain traces of DNA from cancer, known as circulating tumor DNA (ctDNA), are able to help identify which people can successfully stop treatment without a change in their cancer.</li> <li class="seamTextUnorderedListItem">If you have estrogen receptor positive (ER+) breast cancer, you will continue hormone therapy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05721248' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.dana-farber.org/clinical-trials2/detail/22-655/' target='_blank'>Dana-Farber Cancer Institute: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/from-the-experts/mbc-exceptional-responder/' target='_blank'>Metastatic Trial Talk: Why Do Some People Have an Exceptional Response When Being Treated for MBC?</a> </li></ul>

NEAREST SITE: 656 miles Integro Theranostics Research Site #2 Scottsdale,AZ

NCT ID: NCT05900986

Imaging Dye During Surgery for DCIS or Stage I-II Breast Cancer

An Open-label, Single-arm, Phase 1b/2 Study to Investigate the Safety, Efficacy and Pharmacokinetics of LS301-IT in Female Patients Undergoing Partial Mastectomy and Sentinel Lymph Node Biopsy (SLNB) for Ductal Carcinoma in Situ (DCIS) or Stage I-II Primary Invasive Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LS301-IT, by IV, 1 time during surgery</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">LS301-IT is an experimental tracer for imaging scans that may help locate cancer and tumor margins in the body.</li> <li class="seamTextUnorderedListItem">Margins are the area around where the tumor was removed. A negative margin means cancer was not found in the margin, and a positive margin means cancer was found in the margin.</li> <li class="seamTextUnorderedListItem">Your surgeon may use LS301-IT to find and remove all cancer cells during surgery.</li> <li class="seamTextUnorderedListItem">A lumpectomy is sometimes called a partial mastectomy.</li> <li class="seamTextUnorderedListItem">A sentinel lymph node biopsy is used to see if breast cancer cells are found in the sentinel node, the first lymph node under the arm to which the cancer cells are most likely to have spread.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05900986' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://integrotheranostics.com/' target='_blank'>Integro Theranostics: LS301-IT</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/surgery/lumpectomy' target='_blank'>Breastcancer.org: Lumpectomy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/surgery/lymph-node-removal/sentinel-node-dissection' target='_blank'>Breastcancer.org: Sentinel Lymph Node Biopsy</a> </li></ul>

NEAREST SITE: 657 miles Arizona Center for Cancer Care Scottsdale,AZ

NCT ID: NCT04397185

Comparing Two Surgical Techniques to Locate Tumors During a Lumpectomy (Breast Conserving Surgery)

Randomized Prospective Trial of Breast Cancer Locator Guided vs. Wire Localized Partial Mastectomy for Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Breast Cancer Locator</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Breast Cancer Locator used during lumpectomy (breast conserving surgery)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard of care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Wire localizer used during lumpectomy (breast conserving surgery)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Some breast tumors are non-palpable, this means they cannot be felt by touch.</li> <li class="seamTextUnorderedListItem">A wire localizer lumpectomy is when a radiologist inserts a thin wire into the area of the breast with the tumor. The surgeon then uses this wire to find non-palpable tumors.</li> <li class="seamTextUnorderedListItem">The Breast Cancer Locator is a personalized 3D form of the breast. It is an experimental technique that helps the surgeon locate non-palpable tumors during a lumpectomy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04397185' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.brighamandwomens.org/assets/BWH/surgery/surgical-oncology/pdfs/wire-guided-lumpectomy.pdf' target='_blank'>Brighman and Women's Hospital: Wire-Guided Lumpectomy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.komen.org/breast-cancer/treatment/type/surgery/lumpectomy/procedure-information/' target='_blank'>Susan G. Komen: Lumpectomy -- The Procedure</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cairnsurgical.com/breast-cancer-locator/' target='_blank'>CairnSurgical Information Page: Breast Cancer Locator</a> </li></ul>

NEAREST SITE: 657 miles Honor Health Scottsdale,AZ

VISITS: 1 visit per week

NCT ID: NCT05712889

VIP236 Small Molecule Drug Conjugate for Advanced Breast Cancer

An Open-label, Multicenter Phase 1 Study to Characterize Safety, Tolerability, Preliminary Antitumor Activity, Pharmacokinetics, and Pharmacodynamics of VIP236 Monotherapy in Subjects With Advanced Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">VIP236, by IV, weekly</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">VIP236 is an experimental small molecule drug conjugate (SMDC).</li> <li class="seamTextUnorderedListItem">A small molecule drug conjugate (SMDC) is a type of therapy that combines a small molecule that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the small molecule only targets cancer cells, the SMDC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">VIP236's small molecule targets a protein that is expressed by some breast cancer cells and delivers an anti-cancer drug called camptothecin.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05712889' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://vincerx.com/pipeline/' target='_blank'>Vincerx: VIP236 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://investors.vincerx.com/news-releases/news-release-details/vincerx-pharma-announces-fda-safe-proceed-letter-investigational' target='_blank'>Vincerx: VIP236 Press Release</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.sciencedirect.com/science/article/abs/pii/S0223523418310729' target='_blank'>Journal Article: Small Molecule Drug Conjugates</a> </li></ul>

NEAREST SITE: 657 miles HonorHealth Research Institute Scottsdale,AZ

NCT ID: NCT06171789

PRO1107 Antibody Drug Conjugate for Advanced Triple Negative Breast Cancer

A Phase 1/2 Study of PRO1107 in Patients With Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PRO1107, by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PRO1107 is an experimental targeted therapy called an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">The antibody in sacituzumab govitecan (Trodelvy®) targets PTK7 proteins. It delivers the chemotherapy auristatin.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06171789' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 660 miles Mayo Clinic in Arizona Scottsdale,AZ

VISITS: Please contact the research site

NCT ID: NCT03750227

Delivery of Stereotactic Radiation Before or After Brain Surgery for Metastatic Brain Tumors

Pre-Operative vs. Post-Operative Stereotactic Radiosurgery for Operative Metastatic Brain Tumors Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to one of two groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1 (Experimental group)</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">You will receive stereotactic radiosurgery followed by brain surgery within 4 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2 (Control Group)</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">You will undergo brain surgery followed by stereotactic radiosurgery within 2 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiation, also known as stereotactic radiosurgery, delivers high-dose, precisely-targeted radiation in fewer doses than traditional radiation.</li> <li class="seamTextUnorderedListItem">Brain surgery to remove metastases.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03750227' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li></ul>

NCT ID: NCT03979508

Abemaciclib Before Surgery for Women with Stage I-III, Triple Negative or ER Low, HER2- Breast Cancer That Did Not Respond to Chemotherapy

Window Trial of Abemaciclib for Surgically Resectable, Chemotherapy-Resistant, Triple Negative Breast Cancer (a BEAUTY Study*) Scientific Title

• <p class="seamTextPara"> You will receive the following before surgery: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, twice a day, for 2 to 3 weeks</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Biopsy</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Breast cancer that tests positive for 1%-10% estrogen receptors is called ER Low.</li> <li class="seamTextUnorderedListItem">This trial is enrolling women with triple negative as well as ER Low, HER2- breast cancer.</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®) is a CDK 4/6 inhibitor approved to treat HR+ and HER2- metastatic breast cancer.</li> <li class="seamTextUnorderedListItem">Its use in this trial is considered experimental.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03979508' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted_therapies/cdk46-inhibitors' target='_blank'>Breastcancer.org: What Are CDK4/6 Inhibitors?</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.verzenio.com/?utm_source=google&utm_medium=ppc&campaign=6456675261&adgroup=82640243172&ad=378689406892&utm_keyword=kwd-389189556877&gclid=Cj0KCQiAmsrxBRDaARIsANyiD1qSisgRZtObbCNg3aCVnfoCwqXFjJlXYQsig6GLWR1OKy3oM7jjYJIaAtcqEALw_wcB' target='_blank'>Eli Lilly and Company Drug Information Page: Verzenio® (Abemaciclib)</a> </li><li class='seamTextUnorderedListItem'><a href='https://tnbcfoundation.org/' target='_blank'>Triple Negative Breast Cancer Foundation</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/2018/09/01/mbc-news-3/' target='_blank'>Metastatic Trial Talk: Insights Into Treatment Resistance</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523967/' target='_blank'>Journal Article: Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer</a> </li></ul>

NCT ID: NCT04197687

Immunotherapy and Sargramostim After Chemo and Surgery for Women with Stage II-III HER2 Positive Breast Cancer

Phase II Trial to Evaluate Immune-Related Biomarkers for Pathological Response in Stage II-III HER2-Positive Breast Cancer Receiving Neoadjuvant Chemotherapy With Subsequent Randomization to Multi-Epitope HER2 Vaccine vs. Placebo in Patients With Residual Disease Post-Neoadjuvant Chemotherapy Scientific Title

• <p class="seamTextPara"> If you had tumor cells remaining after you received chemotherapy, you will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab emtansine/T-DM1 (Kadcyla®), by IV, for 10.5 months</li> <li class="seamTextUnorderedListItem">TPIV100, by injection, every 3 weeks, for 4.5 months</li> <li class="seamTextUnorderedListItem">Sargramostim, by injection, every 3 weeks, for 4.5 months</li> <li class="seamTextUnorderedListItem">2 boosters of TPIV100 and sargramostim after treatment, at 3 months and 1 year</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Standard Care and Placebo</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab emtansine/T-DM1 (Kadcyla®), by IV, for 10.5 months</li> <li class="seamTextUnorderedListItem">Placebo for TPIV100, by IV, every 3 weeks, for 4.5 months</li> <li class="seamTextUnorderedListItem">Placebo for sargramostim, by injection, every 3 weeks, for 4.5 months</li> <li class="seamTextUnorderedListItem">2 placebo boosters of TPIV100 and sargramostim after treatment, at 3 months and 1 year</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">If you had no tumor cells remaining after you received chemotherapy, you will receive the following:</i> </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®), by IV, for 1 year</li> <li class="seamTextUnorderedListItem">Pertuzumab (Perjeta®), by IV, for 1 year</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">TPIV100 is an experimental vaccine. It may help the body build an immune response (go after) cancer cells that are HER2 positive (HER2+).</li> <li class="seamTextUnorderedListItem">Sargramostim is a drug approved for use during chemotherapy. It helps your body build white blood cells to prevent neutropenia--a low white blood cell count that increases your risk for infection. Its use in this trial is considered experimental.</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®) and pertuzumab (Perjeta®) are HER2-targeted therapies used to treat HER2-positive breast cancer.</li> <li class="seamTextUnorderedListItem">Trastuzumab emtansine/T-DM1 (Kadcyla®) is an antibody-drug conjugate (ADC). It uses trastuzumab to deliver the chemotherapy DM1 directly to the cancer cells. </li> <li class="seamTextUnorderedListItem">Kadcyla® is approved to treat some early-stage HER2 positive (HER2+) breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04197687' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted_therapies/kadcyla' target='_blank'>Breastcancer.org: Trastuzumab emtansine/T-DM1 (Kadcyla®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.org/cancer/breast-cancer/treatment/targeted-therapy-for-breast-cancer.html' target='_blank'>American Cancer Society: Targeted Therapy for Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.markertherapeutics.com/pipeline/tpiv100/' target='_blank'>Drug Company Information Page: TPIV100</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/research-news/csf-meds-lower-neutropenia-risk' target='_blank'>Breastcancer.org: Colony-Stimulating Factor Medicines Slightly Lower Hospitalizations for Low White Blood Cell Counts</a> </li></ul>

VISITS: Coincides with radiation therapy schedule

NCT ID: NCT04443413

Comparing Two Different Types and Schedules of Radiation Therapy in Women with Stage I-III Breast Cancer

A Phase II Trial of Hypofractionated Radiotherapy to the Whole Breast or Post-Mastectomy Chest Wall Including Regional Nodal Irradiation Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">X-ray radiation therapy (photon), 5 times a week, for 5 weeks (25 times in total)</li> <li class="seamTextUnorderedListItem">X-ray radiation therapy boost to the tumor bed </li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Proton radiation therapy, 5 times total</li> <li class="seamTextUnorderedListItem">Proton radiation therapy boost to the tumor bed</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">X-ray radiation therapy is also called photon radiation therapy, and is the standard radiation therapy used to treat breast cancer.</li> <li class="seamTextUnorderedListItem">Proton radiation therapy is a type of radiation treatment that delivers radiation more directly to the cancer cells, making it less likely to damage nearby normal tissues.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04443413' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/radiation' target='_blank'>Breastcancer.org: Radiation Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/radiation/external-beam-radiation-therapy.html' target='_blank'>American Cancer Society: Getting External Beam Radiation Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mayoclinic.org/departments-centers/proton-beam-therapy-program/home/orc-20185488' target='_blank'>Mayo Clinic: Proton Beam Therapy Program</a> </li></ul>

NCT ID: NCT04475640

Genetic Testing for Diverse Groups of People with Breast Cancer

Gemini - Cancer Genetic Testing in Ethnic Populations Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Genetic testing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Genetic testing looks for changes, sometimes called mutations or variants, in your DNA.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04475640' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cdc.gov/genomics/gtesting/genetic_testing.htm' target='_blank'>Centers for Disease and Control: Genetic Testing</a> </li></ul>

VISITS: 1-5 radiation sessions, then 1 visit every 3-6 months for 5 years

NCT ID: NCT05222620

2 Types of Stereotactic Radiosurgery for Brain Metastasis

Phase IIR Trial of Single Fraction Stereotactic Radiosurgery (SRS) Compared With Fractionated SRS (FSRS) for Intact Metastatic Brain Disease (FRACTIONATE) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Single Fraction Stereotactic Radiosurgery, 1 session</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fractionated Stereotactic Radiosurgery, 2-5 sessions</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Radiation therapy uses high-energy x-rays to damage cancer cell DNA. These x-rays stop cancer cells from dividing and growing, thus slowing or stopping tumor growth.</li> </ul> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiation (stereotactic radiosurgery or stereotactic radiotherapy) delivers high-dose, precisely-targeted radiation in fewer doses than traditional radiation therapy.</li> </ul> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Single Fraction Stereotactic Radiosurgery (SFSR) is stereotactic radiation received in one higher dose of radiation given on one day of treatment.</li> </ul> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fractionated Stereotactic Radiation Therapy (FSRT) is stereotactic radiation is divided into several smaller doses (typically 2-5 sessions) of radiation given on separate days of treatment.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05222620' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/radiotherapy/external/types/stereotactic-body-radiotherapy-sbrt' target='_blank'>CancerResearchUK: Stereotactic Radiotherapy (SRT)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mayoclinic.org/tests-procedures/stereotactic-radiosurgery/about/pac-20384526' target='_blank'>Mayo Clinic: Stereotactic Radiosurgery</a> </li></ul>

NCT ID: NCT05417867

Gut Microbiome and Chemotherapy-Induced Nausea in Women with Stage I-III Breast Cancer

A Pilot Study of the Associations Between Chemotherapy-Induced Nausea in Breast Cancer Patients and Gut Microbiome Composition Profiles Scientific Title

• <p class="seamTextPara"> You will complete the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Provide stool samples, 2 times</li> <li class="seamTextUnorderedListItem">Complete questionnaires, 2 times</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The microbiome consists of the many bacteria, viruses, and fungi found in the digestive tract. Most of the microbiome consists of bacteria in your digestive system. These bacteria can be beneficial or harmful. The harmful bacteria cause disease, and the beneficial bacteria help keep you healthy.</li> <li class="seamTextUnorderedListItem">Nausea is a common side effect of many types of chemotherapy.</li> <li class="seamTextUnorderedListItem">You will provide stool samples 2 times: 1) When you begin the trial, and 2) 3-5 days after starting chemotherapy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05417867' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.hsph.harvard.edu/nutritionsource/microbiome/' target='_blank'>Harvard University: What is the Microbiome?</a> </li><li class='seamTextUnorderedListItem'><a href='https://breastcancernow.org/about-us/news-personal-stories/can-gut-bacteria-help-treat-breast-cancer' target='_blank'>Breast Cancer Now: Gut Bacteria and Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment-side-effects/nausea' target='_blank'>Breastcancer.org: Nausea</a> </li></ul>

NCT ID: NCT05557877

Low-Dose Aspirin to Prevent Breast Cancer After Having a Baby

Targeted Prevention of Postpartum-Related Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Biopsy</li> <li class="seamTextUnorderedListItem">Blood tests</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Low-dose aspirin, by mouth, daily</li> </ul> <p class="seamTextPara"> followed by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Blood tests</li> <li class="seamTextUnorderedListItem">Questionnaires</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Low-dose aspirin, a non-steroidal anti-inflammatory drug, may reduce inflammation in blood and tissue which may prevent breast cancer after having a baby.</li> <li class="seamTextUnorderedListItem">Benign breast disease is non-cancerous breast disease.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05557877' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-minute-aspirins-role-in-preventing-and-stopping-the-spread-of-cancer/' target='_blank'>Mayo Clinic: Aspirin and Cancer Prevention</a> </li></ul>

NCT ID: NCT06036875

Survey to Understand How Black and Hispanic Women Perceive Their Risk for Breast Cancer

CARE: Cancer Risk Perception and Women of Color Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Survey, 1 time</li> <li class="seamTextUnorderedListItem">Interview (optional)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">This study is examining the relationship between risk factors for breast cancer and a person's perceptions of those risk factors and if these relationships are different according to race and ethnicity.</li> <li class="seamTextUnorderedListItem">This study is also exploring how people reduce their risk for breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06036875' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NCT ID: NCT06112795

Studying Beliefs About Breast Cancer Risk and Screening Among Hispanic Women in Arizona

Exploring Cultural Acceptability of Community Breast Cancer Risk Assessment Among Hispanic Women in Maricopa County Scientific Title

• <p class="seamTextPara"> You will complete the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Attend an interview or focus group, 1 time</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Hispanic women have fewer mammograms than non-Hispanic white women.</li> <li class="seamTextUnorderedListItem">Education about the importance of breast cancer screening may improve outcomes of Hispanic women.</li> <li class="seamTextUnorderedListItem">This trial is available in English and Spanish.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06112795' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cedars-sinai.org/blog/breast-cancer-risks-latinas.html' target='_blank'>Cedars Sinai: Hispanic Women and Breast Cancer</a> </li></ul>

NEAREST SITE: 666 miles University of Washington Medical Center Seattle,WA

NCT ID: NCT02993068

Stand up to Cancer: Making Genetic Testing Accessible

Stand up to Cancer: MAGENTA (Making Genetic Testing Accessible) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 4 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Watch an online educational video before the testing</li> <li class="seamTextUnorderedListItem">Mail in the saliva collection kit </li> <li class="seamTextUnorderedListItem">Receive an online test results report</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Watch an online educational video before the genetic testing </li> <li class="seamTextUnorderedListItem">Mail in the saliva collection kit </li> <li class="seamTextUnorderedListItem">Receive an online test results report with telephone genetic counseling</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Watch an online educational video with telephone genetic counseling before the testing</li> <li class="seamTextUnorderedListItem">Mail in the saliva collection kit </li> <li class="seamTextUnorderedListItem">Receive an online test results report with telephone genetic counseling </li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 4</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Watch an online educational video with telephone genetic counseling before the testing</li> <li class="seamTextUnorderedListItem">Mail in the saliva collection kit </li> <li class="seamTextUnorderedListItem">Receive an online test results report</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The researchers will see what effects the programs have on a woman's understanding of genetics and quality of life.</li> <li class="seamTextUnorderedListItem">The study is using FDA-approved saliva-testing kits and genetic tests.</li> <li class="seamTextUnorderedListItem">To be eligible for this study, you must meet one of the following: diagnosed with breast cancer at 45 or younger; diagnosed with triple negative (ER-, PR-, HER2-) breast cancer at 60 or younger; have one blood relative with a mutation in BRCA 1, BRCA 2, BRIP1, PALB2, RAD51C, RAD51D, BARD1, MSH2, MSH6, MLH1, or PMS2; have one relative with ovarian cancer; have at least 2 relatives with breast cancer on the same side of the family, one of which is 50 years of age or less; or have one male relative with breast cancer.</li> <li class="seamTextUnorderedListItem">Any woman who tests positive for a genetic mutation will have the ability to speak with a genetic counselor.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02993068' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://magenta.mdanderson.org' target='_blank'>MD Anderson Cancer Center Study Information: MAGENTA</a> </li></ul>

NEAREST SITE: 666 miles University of Washington Seattle,WA

NCT ID: NCT04841148

Preventing Stage II-III ER+, HER2- Breast Cancer with DTCs from Spreading

A Phase II Trial of Avelumab or Hydroxychloroquine With or Without Palbociclib to Eliminate Dormant Breast Cancer (PALAVY) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 4 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Hydroxychloroquine (Plaquenil®), by mouth, daily for 6 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Avelumab (Bavencio®), by IV, every 2 weeks for 6 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Avelumab (Bavencio®), by IV, every 2 weeks for 6 months</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), by mouth, daily for 3 weeks on, 1 week off for 6 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 4</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Hydroxychloroquine (Plaquenil®), by mouth, daily for 6 months</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®), by mouth, daily for 6 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Disseminated tumor cells (DTCs) are single cancer cells that have moved from the tumor to somewhere else in the body, often the bone marrow.</li> <li class="seamTextUnorderedListItem">Hydroxychloroquine (Plaquenil®) is a drug commonly used to prevent and treat malaria. It may also prevent cancer from spreading.</li> <li class="seamTextUnorderedListItem">Palbociclib (Ibrance®) is a type of targeted therapy called a CDK 4/6 inhibitor. CDK 4/6 inhibitors block two enzymes, CDK 4 and CDK 6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">Avelumab (Bavencio®) is a type of immunotherapy called a PD-L1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-L1 may allow the body's immune system to detect and fight cancer cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04841148' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://time.com/2870100/treating-cancer-with-a-malaria-drug/' target='_blank'>TIME: Hydroxychloroquine (Plaquenil®) for Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy' target='_blank'>Breastcancer.org: Avelumab (Bavencio®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/ibrance' target='_blank'>Breastcancer.org: Palbociclib (Ibrance®)</a> </li></ul>

NCT ID: NCT05113927

SELENE System to Reduce Positive Margins During Lumpectomies for Women with DCIS or Stage I-III Breast Cancer

A Prospective, Multi-center, Randomized, Double-arm Trial to Determine the Impact of the SELENE System on Positive Margin Rates in Breast Conservation Surgery. Scientific Title

• <p class="seamTextPara"> You will receive the following (Please contact research site for treatment schedule): </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Standard of Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Standard of care lumpectomy</li> <li class="seamTextUnorderedListItem">Standard of care margin assessment</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Standard of care lumpectomy</li> <li class="seamTextUnorderedListItem">SELENE system margin assessment</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional Procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Questionnaire within 1-3 months after surgery</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The SELENE system uses optical coherence tomography (OCT), a type of light wave technology, to visualize and assess tumor margins during surgery.</li> <li class="seamTextUnorderedListItem">Margins are the area around where the tumor was removed. A negative margin means cancer was not found in the margin, and a positive margin means cancer was found in the margin.</li> <li class="seamTextUnorderedListItem">A lumpectomy is sometimes called a partial mastectomy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05113927' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://perimetermed.com/clinical-trial-enrollment/' target='_blank'>Perimeter Medical Imaging AI: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://perimetermed.com/' target='_blank'>Perimeter Medical Imaging AI: Perimeter OCT Technology</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/surgery/lumpectomy' target='_blank'>Breastcancer.org: Lumpectomy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/pathology-report' target='_blank'>Breastcancer.org: Tumor Margins</a> </li></ul>

NEAREST SITE: 671 miles Banner - MD Anderson Cancer Center Gilbert,AZ

NCT ID: NCT00477100

Breast Cancer Registry for Inflammatory and Other Types of Breast Cancer

Inflammatory Breast Cancer (IBC) Registry Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Additional blood drawn during a routine blood draw</li> <li class="seamTextUnorderedListItem">Core, breast tissue, and skin biopsy (performed for diagnosis)</li> <li class="seamTextUnorderedListItem">Medical history interview</li> <li class="seamTextUnorderedListItem">Clinical data collected from your medical records</li> <li class="seamTextUnorderedListItem">Photographs of both breasts</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Inflammatory breast cancer is a rare, aggressive type of breast cancer in which the cancer cells block the lymph vessels in the skin, causing the breast to appear red and swollen.</li> <li class="seamTextUnorderedListItem">Researchers have not yet identified any genes or other risk factors that they could use to design better treatments for inflammatory breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT00477100' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2006-1072.html' target='_blank'>MD Anderson Cancer Center: Study Website</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.cancer.gov/cancertopics/factsheet/sites-types/ibc' target='_blank'>NCI: Inflammatory Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.breastcancer.org/symptoms/types/inflammatory' target='_blank'>Breastcancer.org: Inflammatory Breast Cancer</a> </li></ul>

NEAREST SITE: 671 miles Banner MD Anderson Cancer Center (BMDACC) Gilbert,AZ

NCT ID: NCT05989724

SON-DP Immunotherapy for Advanced Breast Cancer

A First-in-Human (FIH), Open-Label, Phase Ia/Ib Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SON-DP in Participants With Relapsed/Metastatic Solid Tumors Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">SON-DP, by IV, every 1-2 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">SON-DP is an experimental immunotherapy that may convert cancer cells to normal cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05989724' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 679 miles Swedish Cancer Institute Issaquah,WA

NCT ID: NCT05458674

Targeted Therapy and Chemotherapy for Advanced HER2+ Breast Cancer

A Phase II Study of the Safety, Tolerability and Antitumor Activity of Tucatinib in Combination With Eribulin and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®), by IV, every 3 weeks</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®), by mouth, daily</li> <li class="seamTextUnorderedListItem">Eribulin (Halaven®), by IV, weekly, 2 weeks on, 1 week off</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®) is an anti-HER2 targeted therapy commonly used to treat HER2+ breast cancer.</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®) is a type of targeted therapy called a tyrosine kinase inhibitor. It blocks an enzyme, tyrosine kinase, that helps cancer cells grow.</li> <li class="seamTextUnorderedListItem">Eribulin (Halaven®) is a chemotherapy drug approved to treat metastatic breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05458674' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/herceptin' target='_blank'>Breastcancer.org: Trastuzumab (Herceptin®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/tukysa' target='_blank'>Breastcancer.org: Tucatinib (Tukysa®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/drugs/halaven' target='_blank'>Breastcancer.org: Eribulin (Halaven®)</a> </li></ul>

NEAREST SITE: 680 miles Swedish Cancer Institute Seattle,WA

NCT ID: NCT02701244

Breast Seed Implant Radiation Treatment for Women with DCIS or Early-Stage Breast Cancer

A Multicenter Registry Study of Breast Microseed Treatment for Early Stage Breast Cancer Scientific Title

• <p class="seamTextPara"> You will undergo the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Pre-planning of implantation using CT scan </li> <li class="seamTextUnorderedListItem">Permanent breast seed implantation, an out-patient procedure using local anesthesia and light sedation</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Permanent breast seed implant (PBSI) involves implanting radioactive seeds in a portion of the breast, allowing the patient to live a normal life while the seeds deliver the prescribed radiation to the breast.</li> <li class="seamTextUnorderedListItem">Researchers think that PBSI is a safe and effective alternative to traditional forms of radiation for women who have had a lumpectomy and lymph node dissection or sentinel lymph node biopsy.</li> <li class="seamTextUnorderedListItem">This trial will also create a data registry of women receiving a PBSI so that researchers can study the long-term safety and anti-cancer activity of this type of radiation therapy.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02701244' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.concureoncology.com/clinical-pathway' target='_blank'>Concure Oncology Information Page: Breast Microseed Treatment</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/radiation/internal-radiation-therapy-brachytherapy.html' target='_blank'>American Cancer Society: Internal Radiation Therapy</a> </li></ul>

NEAREST SITE: 681 miles Site 32 - Swedish Medical Center, Swedish Cancer Institute (SCI),Cherry Hill Campus Seattle,WA

NCT ID: NCT05963997

Samuraciclib CDK7 Inhibitor with Elacestrant Hormone Therapy for Advanced ER+, HER2- Breast Cancer with TP53 and ESR1 Mutations

A Phase 1b/2 Open-label Study of Samuraciclib in Combination With Elacestrant in Participants With Metastatic or Locally Advanced Hormone Receptor-positive and Human Epidermal Growth Factor Receptor 2-negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Samuraciclib, by mouth, daily</li> <li class="seamTextUnorderedListItem">Elacestrant (Orserdu®), by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Samuraciclib is an experimental targeted therapy called a CDK7 inhibitor. CDK7 inhibitors may block the CDK7 enzyme that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Elacestrant (Orserdu®) is a type of hormone therapy called a selective estrogen receptor degrader (SERD). SERDs work by binding to and breaking down estrogen receptors.</li> <li class="seamTextUnorderedListItem">If you are premenopausal or perimenopausal, you will also receive a drug that will put you in temporary menopause.</li> <li class="seamTextUnorderedListItem">Targets or mutations: TP53, ESR1</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05963997' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.carricktherapeutics.com/pipeline/cdk7-inhibitor' target='_blank'>Carrick Therapeutics: Samuraciclib Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/orserdu' target='_blank'>Breastcancer.org: Elacestrant (Orserdu®)</a> </li></ul>

NEAREST SITE: 682 miles University of Washington- Seattle,WA

NCT ID: NCT03368729

Niraparib and Herceptin in Women With Metastatic HER2+ Breast Cancer

A Phase 1b/2 Study of the PARP Inhibitor Niraparib in Combination With Trastuzumab in Patients With Metastatic HER2+ Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Niraparib (Zejula®), by mouth, daily, ongoing</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®), by IV, every 3 weeks, ongoing</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Zejula is at type of targeted therapy called a PARP inhibitor. It works by blocking poly (ADP-ribose) polymerase, an enzyme that helps cancer cells grow by repairing their DNA. It is approved to treat women with certain types of reproductive cancers. Its use in breast cancer is considered experimental. </li> <li class="seamTextUnorderedListItem">Herceptin is a HER2-targeted therapy approved to treat HER2 positive breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT03368729' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.zejula.com/en' target='_blank'>Drug Company Information Page: Zejula® (Niraparib)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted_therapies/herceptin?gclid=Cj0KCQiAyKrxBRDHARIsAKCzn8zEHqEyTfwjNEW138WZ4GeUdB3CVmQfk-GJ5zPldOhQ2p6lEMBu1fsaAt6rEALw_wcB' target='_blank'>Breastcancer.org: Herceptin</a> </li><li class='seamTextUnorderedListItem'><a href='https://breastcancernow.org/information-support/facing-breast-cancer/going-through-breast-cancer-treatment/parp-inhibitors-in-breast-cancer-treatment' target='_blank'>Breast Cancer Now: PARP Inhibitors in Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.sciencedaily.com/releases/2012/09/120917084946.htm' target='_blank'>ScienceDaily: PARP Inhibitors May Have Clinical Utility in HER2-positive Breast Cancers</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.ncbi.nlm.nih.gov/pubmed/25128455' target='_blank'>PubMed Abstract: Poly (ADP-ribose) Polymerase Inhibition Enhances Trastuzumab Antitumour Activity in HER2 Overexpressing Breast Cancer.</a> </li></ul>

NEAREST SITE: 682 miles University of Washington Seattle,WA

VISITS: 3 visits in 1 year

NCT ID: NCT04248257

Peer Support For Young Adult Women With High Breast Cancer Risk

Peer Support For Young Adult Women With High Breast Cancer Risk Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Experimental</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PeACE counseling sessions, by phone, 3 times</li> <li class="seamTextUnorderedListItem">Interviews, 3 times</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Usual Care</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Navigation to peer support services</li> <li class="seamTextUnorderedListItem">Interviews, 3 times</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PeACE counseling sessions are led by peer coaches.</li> <li class="seamTextUnorderedListItem">If you are in Group 2, you will receive navigation to peer support with a range of community groups who provide these services.</li> <li class="seamTextUnorderedListItem">This trial is also available in Spanish.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04248257' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 682 miles Fred Hutch/University of Washington Cancer Consortium Seattle,WA

VISITS: 1 or 2 visits a week, for 3 months before surgery

NCT ID: NCT04329065

WOKVAC Vaccine with Chemotherapy and Two Anti-HER2 Targeted Therapies Before Surgery for Stage I-III, HER2 Positive, HR Negative Breast Cancer

A Phase II Study of Concurrent WOKVAC Vaccination With Neoadjuvant Chemotherapy and HER2-Targeted Monoclonal Antibody Therapy Scientific Title

• <p class="seamTextPara"> You will receive the following for three months before surgery: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">WOKVAC vaccine, by injection, 3 times</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®), by IV, every week (2 weeks on, 1 week off)</li> <li class="seamTextUnorderedListItem">Trastuzumab (Herceptin®), by IV, every 3 weeks</li> <li class="seamTextUnorderedListItem">Pertuzumab, (Perjeta®), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">WOKVAC is an experimental vaccine designed to stimulate your immune system to go after and kill cancer cells.</li> <li class="seamTextUnorderedListItem">Paclitaxel (Taxol®) is a chemotherapy routinely used to treat breast cancer.</li> <li class="seamTextUnorderedListItem">Pertuzumab (Perjeta®) and trastuzumab (Herceptin®) are HER2-targeted therapies used to treat HER2 positive (HER2+) breast cancer.</li> <li class="seamTextUnorderedListItem">Pertuzumab (Perjeta®) is approved to treat early-stage HER2 positive breast cancer with tumors 2 cm or larger or with positive lymph nodes. It's use in this trial may be considered experimental depending upon the size of your tumors and if your lymph nodes are positive for cancer cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04329065' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.wingsofkaren.org/dr-king---dr-disis' target='_blank'>Wings of Karen: WOKVAC Vaccine</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.komen.org/breast-cancer/treatment/type/neoadjuvant-therapy/' target='_blank'>Susan G. Komen: Neoadjuvant Therapies for Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/research-news/perjeta-plus-herceptin-and-chemo-shows-benefits' target='_blank'>Breastcancer.org: Adding Perjeta to Herceptin and Chemotherapy After Surgery Shows Benefits in Early-Stage HER2-Positive Breast Cancer</a> </li></ul>

NEAREST SITE: 682 miles University of Washington / Fred Hutchinson Cancer Center Seattle,WA

VISITS: 1 visit every 3 weeks, for 4.5 months before surgery

NCT ID: NCT04584255

PARP Inhibitor & Experimental Immunotherapy Before Surgery for Stage I-III, HER2- Breast Cancer with an Inherited BRCA1/2 Mutation

A Phase II Study of Niraparib With Dostarlimab Therapy as Neoadjuvant Treatment for Patients With BRCA-mutated Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following for 4.5 months before surgery: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Niraparib (Zejula®), by mouth, daily</li> <li class="seamTextUnorderedListItem">TSR042 (Dostarlimab), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Niraparib (Zejula®) is a type of targeted therapy called a PARP inhibitor. It is approved for ovarian cancer, but its use in this trial is considered experimental.</li> <li class="seamTextUnorderedListItem">PARP inhibitors work by blocking the enzyme poly (ADP-ribose) polymerase--this enzyme helps cancer cells grow by repairing their DNA.</li> <li class="seamTextUnorderedListItem">Dostarlimab (TSR-042, Jemperli®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04584255' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://chemocare.com/chemotherapy/drug-info/niraparib.aspx' target='_blank'>Chemocare.com: Niraparib (Zejula®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://immuno-oncologynews.com/tsr-042/' target='_blank'>Immuno-Oncology News: TSR-042 (Dostarlimab)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.zejula.com/en/hcp?cc=ps_2YZEQ6MXT1779794&mcm=220010&gclid=CjwKCAiA6aSABhApEiwA6Cbm_0dmoMN1fy65sxQRaJ4tJP5pyrjG7Zxa2N3W9SHd9XoaJLkymSF0NhoCy6EQAvD_BwE' target='_blank'>GSK Drug Information Page: Zejula® (Niraparib)</a> </li></ul>

VISITS: 1 visit every 3 weeks for 3 months, then every 6 weeks, ongoing

NCT ID: NCT04673448

Niraparib and Dostarlimab for BRCA+ Advanced Breast Cancer

Phase IB Trial of Niraparib and TSR-042 in Patients With BRCA-Mutated Breast, Pancreas or Ovary Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Niraparib (Zejula®), by mouth, twice a day, ongoing</li> <li class="seamTextUnorderedListItem">Dostarlimab (TSR-042, Jemperli®), by IV, every 3 weeks (4 times), then every 6 weeks, ongoing</li> <li class="seamTextUnorderedListItem">2 biopsies</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Niraparib (Zejula®) is a type of targeted therapy called a PARP inhibitor. It works by blocking poly (ADP-ribose) polymerase, an enzyme that helps cancer cells grow by repairing their DNA. </li> <li class="seamTextUnorderedListItem">Dostarlimab (TSR-042, Jemperli®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of advanced cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: BRCA1 or BRCA2 hereditary (genetic) or tumor-based (genomic)</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04673448' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/from-the-experts/genetic-vs-genomic-testing/' target='_blank'>Metastatic Trial Talk: Genetic vs. Genomic Testing</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancernetwork.com/view/dostarlimab-gains-new-fda-approved-indication-mismatch-repair-deficient-tumors' target='_blank'>CancerNetwork: Dostarlimab Gains New FDA-Approved Indication for Treatment of Mismatch Repair–Deficient Tumors</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a621030.html' target='_blank'>MedLinePlus: Dostarlimab</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/parp-inhibitors-cancer/' target='_blank'>Metastatic Trial Talk: PARP Inhibitors</a> </li></ul>

NEAREST SITE: 682 miles Fred Hutchinson Cancer Center Seattle,WA

NCT ID: NCT04969835

AVA6000 Chemotherapy for Advanced Breast Cancer

A Phase 1, Open Label, Dose-Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics and Initial Therapeutic Activity of AVA6000, a Novel FAP-activated Doxorubicin Prodrug Administered Intravenously in Patients With Locally Advanced or Metastatic Selected Solid Tumours Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">AVA6000, by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">AVA6000 is an experimental form of doxorubicin chemotherapy.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04969835' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://avacta.com/therapeutics/precision/' target='_blank'>Avacta Life Sciences: AVA6000 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/chemotherapy' target='_blank'>Breastcancer.org: Chemotherapy</a> </li></ul>

VISITS: 1 visit every week for 6 months, then 1 visit every 2-4 weeks

NCT ID: NCT05098210

Personalized Vaccine with Immunotherapy for Metastatic HR+, HER2- Breast Cancer

PNV21-001: A Phase I Study of a Personalized Multi-Peptide Neo-Antigen Vaccine in Breast Cancer and PD1/PD-L1 Inhibitor-Refractory Melanoma Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Poly ICLC, by injection, weekly for 2 weeks</li> </ul> <p class="seamTextPara"> followed 2 weeks later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Personalized neoantigen peptide vaccine, by injection, monthly for 6 months</li> <li class="seamTextUnorderedListItem">Nivolumab (Opdivo®), by IV, every 2-4 weeks for 6 months</li> <li class="seamTextUnorderedListItem">Poly ICLC, by injection, weekly, 3 weeks on, 1 week off</li> </ul> <p class="seamTextPara"> followed 6 months later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Nivolumab (Opdivo®), by IV, every 2-4 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Personalized neoantigen peptide vaccines are an experimental type of immunotherapy. The vaccine is designed to target certain proteins (neoantigens) on tumor cells.</li> <li class="seamTextUnorderedListItem">Nivolumab (Opdivo®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">Poly ICLC is an immunotherapy that stimulates your immune system to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05098210' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.bcrf.org/breast-cancer-vaccine-explainer/' target='_blank'>Breast Cancer Research Foundation: Breast Cancer Vaccines</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/immunotherapy' target='_blank'>Breastcancer.org: Nivolumab (Opdivo®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/publications/dictionaries/cancer-terms/def/poly-iclc' target='_blank'>National Cancer Institute: Poly ICLC</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/immune-checkpoint-inhibitor/' target='_blank'>Metastatic Trial Talk: Update on Immunotherapy for MBC: Immune Checkpoint Inhibitors</a> </li></ul>

VISITS: 1 visit per month for 3 months, then 2 visits within 9 months

NCT ID: NCT05455658

STEMVAC Vaccine for Stage I-III Triple Negative Breast Cancer

A Phase II Trial of The Immunogenicity of a DNA Plasmid Based Vaccine (STEMVAC) Encoding Th1 Selective Epitopes From Five Antigens Associated With Breast Cancer Stem Cells (MDM2, YB1, SOX2, CDC25B, CD105) in Participants With Early Stage Triple Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">STEMVAC vaccine, by injection, monthly for 3 months, then 2 times within 9 months</li> <li class="seamTextUnorderedListItem">Sargramostim, by injection, monthly for 3 months, then 2 times within 9 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The STEMVAC vaccine is an experimental immunotherapy that targets proteins on some breast cancer cells to boost the immune system to recognize and destroy some cancer cell proteins.</li> <li class="seamTextUnorderedListItem">Sargramostim is a type of immunotherapy that stimulates your body to produce more immune cells to detect and fight cancer cells.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+ or 2+.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05455658' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.uwcvi.org/post/2020-review-vaccine-and-clinical-trials' target='_blank'>University of Washington Cancer Vaccine Insititute: STEMVAC Vaccine</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a693005.html' target='_blank'>MedlinePlus: Sargramostim</a> </li></ul>

VISITS: 3 visits in 1 month, then 1 visit every 3 months

NCT ID: NCT06179303

PET/CT Scan to Predict Response to Abemaciclib for Advanced ER+, HER2- Breast Cancer

A Phase II Trial to Evaluate Functional Imaging in Prediction of Response to Abemaciclib for Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">PET/CT scan with FFNP, by IV, 3 times in 1 month, then every 3 months</li> <li class="seamTextUnorderedListItem">Estradiol, by mouth, 1 day</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, daily</li> <li class="seamTextUnorderedListItem">Standard of care hormone therapy</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®) is a type of targeted therapy called a CDK4/6 inhibitor. CDK4/6 inhibitors block two proteins, CDK4 and CDK6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">FFNP PET/CT imaging is a form of x-ray that uses FFNP as an imaging agent that may provide more precise information about the location of tumors that <q>light up</q> with FFNP than a PET scan alone can provide.</li> <li class="seamTextUnorderedListItem">Estradiol is type of hormone therapy for advanced ER+ breast cancer.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+ or FISH -.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06179303' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 733 miles Cancer Care Northwest Spokane Valley,WA

NCT ID: NCT04791384

Elacestrant Hormone Therapy and Abemaciclib CDK 4/6 Inhibitor for Metastatic HR+, HER2- Breast Cancer with Brain or Leptomeningeal Metastasis

Multicenter Open Label Phase Ib/II Trial of Abemaciclib and Elacestrant in Patients With Brain Metastasis Due to HR+/Her2- Breast Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®), by mouth, daily</li> <li class="seamTextUnorderedListItem">Elacestrant, by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Elacestrant is an experimental hormone therapy called a selective estrogen receptor degrader (SERD). SERDs work by binding to and breaking down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Abemaciclib (Verzenio®) is a type of targeted therapy called a CDK 4/6 inhibitor. CDK 4/6 inhibitors block two proteins, CDK4 and CDK6, that help cancer grow.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women will also be given a drug that will put women in temporary menopause.</li> <li class="seamTextUnorderedListItem">In this trial, HER2 low is defined as IHC 1+.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04791384' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.onclive.com/view/benefit-of-elacestrant-improves-with-longer-duration-of-cdk4-6-inhibition-in-patients-with-er-her2-metastatic-breast-cancer' target='_blank'>OncLive: Benefit of Elacestrant Improves With Longer Duration of CDK4/6 Inhibition in People With ER+/HER2- Metastatic Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.targetedonc.com/view/the-emerald-trial-elacestrant-mechanism-of-action-study-design-and-outcomes' target='_blank'>Targeted Oncology: Elacestrant for ER+, HER2- MBC</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/verzenio' target='_blank'>Breastcancer.org: Abemaciclib (Verzenio®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/oral-serds/' target='_blank'>Metastatic Trial Talk: Update on Oral SERDs for Estrogen Receptor-Positive MBC</a> </li></ul>

NEAREST SITE: 735 miles Cancer Care Northwest Spokane Valley,WA

NCT ID: NCT06072612

Bria-IMT Cell Therapy for Advanced Breast Cancer

Randomized, Open-Label Study of the Bria-IMT Regimen and Check Point Inhibitor vs Physicians' Choice in Advanced Metastatic Breast Cancer. Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 3 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Bria-IMT Regimen with Immunotherapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®), by IV, 1 day every 3 weeks</li> <li class="seamTextUnorderedListItem">SV-BR-1-GM, by injection, 4 days every 3 weeks</li> <li class="seamTextUnorderedListItem">Interferon, 4 days every 3 weeks</li> <li class="seamTextUnorderedListItem">Retifanlimab (Zynyz®), by infusion, every 3 weeks</li> <li class="seamTextUnorderedListItem">Imaging scans, every 1-2 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Bria-IMT Regimen Alone</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Cyclophosphamide (Cytoxan®), by IV, 1 day every 3 weeks</li> <li class="seamTextUnorderedListItem">SV-BR-1-GM, by injection, 4 days every 3 weeks</li> <li class="seamTextUnorderedListItem">Interferon, 4 days every 3 weeks</li> <li class="seamTextUnorderedListItem">Imaging scans, every 1-2 months</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3: Chemotherapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Chemotherapy</li> <li class="seamTextUnorderedListItem">Imaging scans, every 1-2 months</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The Bria-IMT regimen is an experimental cell therapy with SV-BR-1-GM cells.</li> <li class="seamTextUnorderedListItem">Before you receive the cell therapy, you will receive cyclophosphamide (Cytoxan®) chemotherapy to prepare your body to receive the cells.</li> <li class="seamTextUnorderedListItem">Interferon is an immunotherapy used to regulate your immune response to the cell therapy.</li> <li class="seamTextUnorderedListItem">Retifanlimab (Zynyz®) is a type of immunotherapy called a PD-1 inhibitor, which is a type of immune checkpoint inhibitor. Blocking PD-1 may allow the body's immune system to detect and fight cancer cells.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06072612' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/adoptive-cell-therapy-2-2/' target='_blank'>Metastatic Trial Talk: Adoptive Cell Therapies: A Type of Immunotherapy for MBC</a> </li><li class='seamTextUnorderedListItem'><a href='https://briacell.com/briaimt/' target='_blank'>BriaCell Therapeutics: Bria-IMT Cell Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.gov/about-cancer/treatment/drugs/retifanlimab-dlwr' target='_blank'>National Cancer Institute: Retifanlimab (Zynyz®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/chemotherapy' target='_blank'>Breastcancer.org: Chemotherapy</a> </li></ul>

NEAREST SITE: 744 miles Center for Indigenous Health Whiteriver,AZ

NCT ID: NCT05665660

Culturally Relevant Education and Coaching to Improve Breast Cancer Screening in American Indian or Alaska Native Women

Developing and Evaluating Scalable and Culturally Relevant Interventions to Improve Breast Cancer Screening Among White Mountain Apache Women Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CARE: Complete mammogram education course</li> <li class="seamTextUnorderedListItem">COACH: Access to an Apache women's health coach</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CARE: Complete mammogram education course</li> </ul> <p class="seamTextPara"> followed 3 months later by: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">COACH: Access to an Apache women's health coach (optional)</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">CARE refers to a mammogram education course.</li> <li class="seamTextUnorderedListItem">COACH refers to access to an Apache women's health coach and navigator who will help you receive breast cancer screening.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05665660' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://americanindiancancer.org/aicaf-project/breast-cancer-awareness/' target='_blank'>American Indian Cancer Foundation: Breast Cancer in American Indian Women</a> </li><li class='seamTextUnorderedListItem'><a href='https://ascopost.com/news/march-2023/regardless-of-income-american-indiannative-american-women-may-be-less-likely-to-undergo-mammography-than-white-women/' target='_blank'>ASCO Post: American Indian Women and Mammography</a> </li></ul>

NEAREST SITE: 752 miles The University of Arizona Cancer Center Tucson,AZ

NCT ID: NCT05216432

RLY-2608 Alone and With Fulvestrant for Advanced Breast Cancer with a PIK3CA Mutation

A First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Advanced Solid Tumor Patients and in Combination With Fulvestrant in Patients With Advanced Breast Cancer Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups based on when you enroll: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">RLY-2608, by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">RLY-2608, by mouth</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Additional procedures</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">May require a biopsy</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule.</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">RLY-2608 is an experimental targeted therapy called a PI3K inhibitor.</li> <li class="seamTextUnorderedListItem">If there is a mutation in the PIK3CA gene, the PI3K pathway can become overactivated which allows cancer cells to grow.</li> <li class="seamTextUnorderedListItem">RLY-2608 may block the PI3K pathway.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a hormone therapy approved to treat postmenopausal women with advanced breast cancer.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor degrader (SERD).</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Targets or mutations: PIK3CA</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05216432' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy' target='_blank'>Breastcancer.org: Targeted Therapy</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://ir.relaytx.com/news-releases/news-release-details/relay-therapeutics-announces-dosing-first-patient-first-human-0' target='_blank'>Relay Therapeutics Press Release: RLY-2608</a> </li></ul>

NEAREST SITE: 804 miles Bozeman Health Deaconess Hospital Bozeman,MT

VISITS: One visit every year

NCT ID: NCT02012699

iCaRe2: Integrated Cancer Data Repository for Cancer Research

Integrated Cancer Repository for Cancer Research Scientific Title

• <p class="seamTextPara"> This is a data collection (registry) study. You will: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Provide biospecimens (blood, urine, tissue) for the biobank</li> <li class="seamTextUnorderedListItem">Complete questionnaires, once a year</li> <li class="seamTextUnorderedListItem">Participate in follow-up visits with your healthcare provider, once a year</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Research sites will implement and maintain a comprehensive data and biospecimen bank known as the Integrated Cancer Repository for Cancer Research (iCaRe2). </li> <li class="seamTextUnorderedListItem">Participants will provide blood, urine and tissue samples for the biobank. </li> <li class="seamTextUnorderedListItem">The data registry and biospecimen bank is made available for research on cancer and other chronic diseases.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT02012699' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://icare2project.org' target='_blank'>iCaRe2 Project</a> </li></ul>

NEAREST SITE: 860 miles Vail Health Shaw Cancer Center Edwards,CO

VISITS: 7 visits within 2 years

NCT ID: NCT05637216

Losartan to Reduce Fibrosis for People with Stage 0-IV Breast Cancer

A Pilot Study of Losartan to Reduce Radiation Induced Fibrosis in Breast Cancer Patients Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Losartan, by mouth, daily during radiation until 1 year after radiation</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Placebo for losartan, by mouth, daily during radiation until 1 year after radiation</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Losartan is an FDA approved blood pressure medication that may also decrease fibrosis.</li> <li class="seamTextUnorderedListItem">Fibrosis is the thickening or scarring of tissue and can be caused by radiation.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05637216' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.cancer.org/cancer/types/breast-cancer/non-cancerous-breast-conditions/fibrosis-and-simple-cysts-in-the-breast.html#:~:text=Neither%20fibrosis%20nor%20simple%20cysts,is%20found%20on%20a%20biopsy.' target='_blank'>American Cancer Society: Breast Fibrosis</a> </li><li class='seamTextUnorderedListItem'><a href='https://medlineplus.gov/druginfo/meds/a695008.html' target='_blank'>Medline Plus: Losartan</a> </li></ul>

NEAREST SITE: 895 miles Lovelace Medical Center-Saint Joseph Square Albuquerque,NM

VISITS: 1-5 visits within 1-2 weeks

NCT ID: NCT05703269

Single vs. Multiple Doses of Radiation with Immunotherapy for Breast Cancer with Brain Metastasis

Hypofractionated Radiotherapy vs Single Fraction Radiosurgery for Brain Metastasis Patients on Immunotherapy (HYPOGRYPHE) Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Single Radiation Dose</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Single fraction stereotactic radiosurgery (SSRS), 1 time</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Multiple Radiation Doses</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fractionated stereotactic radiosurgery (FSRS), 3-5 times within 3-10 days</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Stereotactic radiation (stereotactic radiosurgery) delivers high-dose, precisely-targeted radiation in fewer doses than traditional radiation therapy.</li> <li class="seamTextUnorderedListItem">Single fraction stereotactic radiosurgery (SSRS) uses a higher dose of radiation in a single dose.</li> <li class="seamTextUnorderedListItem">SSRS has recently become a standard of care treatment for people with 1-4 brain metastases and is also commonly used for people with up to 15 metastases.</li> <li class="seamTextUnorderedListItem">Fractionated stereotactic radiosurgery (FSRS) uses a lower dose of radiation over 3 to 5 treatments given daily or every other day.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05703269' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://mbcbrainmets.org/' target='_blank'>MBCBrainMets.org</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.mayoclinic.org/tests-procedures/stereotactic-radiosurgery/about/pac-20384526' target='_blank'>Mayo Clinic: Stereotactic Radiation</a> </li></ul>

NEAREST SITE: 896 miles University of New Mexico Comprehensive Cancer Center Albuquerque,NM

NCT ID: NCT06260332

Physical Activity with Health Coach to Decrease Pain After Surgery for Hispanic Women

Move Toward Recovery: A Physical Activity Intervention to Reduce Persistent Pain Following Breast Surgery for Cancer in Young, Hispanic Women Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Fitbit to monitor physical activity, daily for 3 months</li> <li class="seamTextUnorderedListItem">Phone calls with health coach, 6 times within 3 months</li> <li class="seamTextUnorderedListItem">Education materials</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Staying active is important for physical, mental, and social health and well-being.</li> <li class="seamTextUnorderedListItem">Moving more could also reduce pain and associated stress, anxiety, or depression.</li> <li class="seamTextUnorderedListItem">Wearable devices such as FitBits are used to track your physical activity.</li> <li class="seamTextUnorderedListItem">Using a fitness tracker may help people move more, whether or not they choose to exercise.</li> <li class="seamTextUnorderedListItem">This trial is also available in Spanish.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06260332' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NEAREST SITE: 936 miles Rocky Mountain Cancer Centers - Boulder Boulder,CO

VISITS: 5 visits over 5 days

NCT ID: NCT01185132

Intensity-Modulated Radiation Therapy After Lumpectomy

A Phase III Randomized Study Comparing Intensity Modulated Planning Versus 3-Dimensional Planning for Accelerated Partial Breast Radiotherapy Scientific Title

• <p class="seamTextPara"> Participants will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Intensity-Modulated Radiotherapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Intensity-modulated radiotherapy over 5 days</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: 3D-Conformal External Beam Radiotherapy</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">3D-conformal external beam radiotherapy over 5 days</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Women whose breast cancer treatment includes a lumpectomy almost always receive radiation as well. </li> <li class="seamTextUnorderedListItem">Intensity-modulated radiation therapy is a type of high-precision radiotherapy that can more precisely deliver radiation to the three-dimensional (3-D) shape of the tumor. </li> <li class="seamTextUnorderedListItem">This allows higher radiation doses to be focused on the site of the tumor while minimizing the amount of radiation the surrounding normal breast and lung tissue receive.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT01185132' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.radiologyinfo.org/en/info.cfm?pg=imrt' target='_blank'>RadiologyInfo.org: IMRT</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.cancercenter.com/treatments/intensity-modulated-radiation-therapy/' target='_blank'>CamcerCemter.com: IMRT Video</a> </li><li class='seamTextUnorderedListItem'><a href='https://rockymountaincancercenters.com/innovative-treatments/radiation-therapy-services#IMRT' target='_blank'>Rocky Mountain Cancer Center: IMRT</a> </li></ul>

NEAREST SITE: 941 miles University of Colorado Denver Aurora,CO

NCT ID: NCT01503190

Immune System Response to Breast Cancer in Women Under Age 50

A Translational Study of the Interactions Between Prior Pregnancy and the Biologic Subtype of Breast Cancer in Defining the Cancer: Host Immunologic Interaction Scientific Title

• <p class="seamTextPara"> All participants will provide the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Tissue, blood and urine samples, if recently diagnosed</li> <li class="seamTextUnorderedListItem">Tissue donation only, if enrolled after treatment has begun or has ended</li></ul>
• <p class="seamTextPara"> Researchers are interested in learning more about the role the immune system plays in cancer. </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">This study is looking specifically at the level of immune suppression seen in breast cancer that occurs in women under age 50.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT01503190' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.breastcancer.org/tips/immune/' target='_blank'>BreastCancer.org: Understanding Your Immune System</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.youngsurvival.org/' target='_blank'>Young Survival Coalition</a> </li><li class='seamTextUnorderedListItem'><a href='http://www.ucdenver.edu/academics/colleges/medicalschool/departments/medicine/MedicalOncology/faculty/Pages/VirginiaFBorges,MD.aspx' target='_blank'>Study PI: Virginia F. Borges, MD</a> </li></ul>

NEAREST SITE: 941 miles University of Colorado Hospital Aurora,CO

NCT ID: NCT04558138

Mastectomy with Immediate Reconstruction With or Without Spending the Night in the Hospital

A Randomized Controlled Trial in Patients Undergoing Immediate Implant-Based Breast Reconstruction Utilizing an Enhanced Recovery Pathway Comparing Outcomes and Patient Satisfaction Based on Time of Discharge Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1: Not Spending the Night in the Hospital</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Released from hospital the day of surgery</li> <li class="seamTextUnorderedListItem">Questionnaires, 2 times in 1 week</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2: Spending the Night in the Hospital</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Released from hospital the day after surgery</li> <li class="seamTextUnorderedListItem">Questionnaires, 2 times in 1 week</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Traditionally people undergoing a mastectomy with immediate reconstruction are admitted to the hospital overnight.</li> <li class="seamTextUnorderedListItem">This trial will study whether discharge on the same day of surgery poses any major risks compared to discharge the day after surgery.</li> <li class="seamTextUnorderedListItem">This trial is also available in Spanish.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT04558138' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/surgery/mastectomy' target='_blank'>Breastcancer.org: Mastectomy</a> </li></ul>

NCT ID: NCT05138510

Sexual Health in People with DCIS and Stage I-IV Breast Cancer

Sexuality and Breast Cancer: Developing Appropriate Education for Women Going Through Treatment Scientific Title

• <p class="seamTextPara"> You will participate the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Virtual focus group</li> <li class="seamTextUnorderedListItem">Questionnaires</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Providers will lead the virtual focus groups over Zoom.</li> <li class="seamTextUnorderedListItem">Focus group findings will be used to create appropriate educational material that will address the sexual health needs of people with breast cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05138510' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/managing-life/sex-intimacy' target='_blank'>Breastcancer.org: Sexual Health During and After Breast Cancer</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/types/metastatic/sexuality' target='_blank'>Breastcancer.org: Sexuality and Metastatic Breast Cancer</a> </li></ul>

NEAREST SITE: 941 miles University of Colorado Cancer Center Aurora,CO

NCT ID: NCT05230810

Targeted Therapy for Metastatic HER2+ Breast Cancer with a PIK3CA Mutation

This is a Multicenter, Single Arm, Open-label, run-in Phase Ib / Roll-over Phase II Study of Tucatinib in Combination With Alpelisib in Subjects With PIK3CA-mutant HER2-positive Locally Advanced Unresectable or Metastatic Breast Cancer. Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®), by mouth, daily</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa), by mouth, daily</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection (for people with HR positive breast cancer)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Please contact research site for treatment schedule</i></p>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Alpelisib (Piqray®) is a type of targeted therapy called a PI3K inhibitor. Blocking the PI3K pathway may slow or stop cancer cells from growing.</li> <li class="seamTextUnorderedListItem">Tucatinib (Tukysa®) is a type of anti-HER2 targeted therapy called a tyrosine kinase inhibitor. It blocks an enzyme, tyrosine kinase, that helps HER2+ cancer cells grow.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor downregulator (SERD). SERDs bind to and break down estrogen receptors. You will only receive fulvestrant (Faslodex®) if you have HR+ (ER+ and/or PR+) breast cancer.</li> <li class="seamTextUnorderedListItem">Premenopausal and perimenopausal women with HR+ breast cancer will also be given a drug that will put women in temporary menopause.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05230810' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/piqray' target='_blank'>Breastcancer.org: Alpelisib (Piqray®)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/tukysa' target='_blank'>Breastcancer.org: Tucatinib (Tukysa)</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/hormonal-therapy/faslodex' target='_blank'>Breastcancer.org: Fulvestrant (Faslodex®)</a> </li></ul>

NEAREST SITE: 941 miles University of Colorado - Anschutz Medical Campus - PPDS Aurora,CO

NCT ID: NCT05650879

ELVN-002 Targeted Therapy for Advanced HER2 Positive or HER2 Mutated Breast Cancer

A Phase 1a/1b Study of ELVN-002 for the Treatment of Patients With HER2 Mutant Non-Small Cell Lung Cancer Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ELVN-002, by mouth, daily</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ELVN-002, by mouth, daily</li> <li class="seamTextUnorderedListItem">Trastuzumab emtansine (Kadcyla®, T-DM1), by IV, every 3 weeks</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">ELVN-002 is an experimental anti-HER2 targeted therapy that targets the HER2 protein on breast cancer cells.</li> <li class="seamTextUnorderedListItem">Trastuzumab emtansine (Kadcyla®, T-DM1) is an antibody drug conjugate (ADC).</li> <li class="seamTextUnorderedListItem">An antibody-drug conjugate (ADC) is a type of therapy that combines an antibody that targets cancer cells with a therapy that can kill cancer cells.</li> <li class="seamTextUnorderedListItem">Because the antibody only targets cancer cells, the ADC does not kill normal cells, making it less likely to cause side effects.</li> <li class="seamTextUnorderedListItem">Trastuzumab emtansine (Kadcyla®, T-DM1)'s antibody targets HER2, a protein that is expressed by some breast cancer cells, and it delivers an anti-cancer drug called emtansine.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05650879' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.enliventherapeutics.com/pipeline/' target='_blank'>Enliven Therapeutics: ELVN-002 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.breastcancer.org/treatment/targeted-therapy/kadcyla' target='_blank'>Breastcancer.org: Trastuzumab Emtansine (Kadcyla®, T-DM1)</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/antibody-drug-conjugates/' target='_blank'>Metastatic Trial Talk: Update On Antibody-Drug Conjugates (ADCs) For MBC</a> </li></ul>

NCT ID: NCT05871008

Health Risk Assessment Before Treatment for People 65+ with Stage I-IV Breast Cancer

Integrated Actionable Aging Assessment for Cancer Patients Pilot Scientific Title

• <p class="seamTextPara"> You will be randomly assigned to 1 of 3 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Health risk assessment including social determinants of health (SDOH)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Health risk assessment not including social determinants of health (SDOH)</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 3</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Usual care</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">The web-based health risk assessment and feedback system identifies unhealthy behaviors, mental health status, and patient concerns.</li> <li class="seamTextUnorderedListItem">Social determinants of health (SDOH) describe non-medical factors that influence your health, such as race, gender identity, education, occupation, transportation, food and health access, medication affordability, safety at home, housing, and financial stability.</li> <li class="seamTextUnorderedListItem">This trial is enrolling people who speak English or Spanish.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05871008' target='_blank'>ClinicalTrials.gov</a> </li></ul>

NCT ID: NCT05902988

VLS-1488 Targeted Therapy for Advanced Triple Negative Breast Cancer

A Phase I/II Study of VLS-1488 (an Oral KIF18A Inhibitor) in Subjects With Advanced Cancer Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">VLS-1488, by mouth</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">VLS-1488 is an experimental targeted therapy called a KIF18A inhibitor. KIF18A inhibitors may slow or stop cancer cells from growing.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT05902988' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.volastratx.com/pipeline/' target='_blank'>Volastra Therapeutics: VLS-1488 Drug Information Page</a> </li></ul>

NEAREST SITE: 945 miles Sarah Cannon Research Institute (Scri) At Health One Denver,CO

NCT ID: NCT06120283

BGB-43395 CDK4 Inhibitor Alone or with Hormone Therapy for Advanced HR+, HER2- Breast Cancer

A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of the CDK4 Inhibitor BGB-43395, Alone or as Part of Combination Therapies in Patients With Metastatic HR+/HER2- Breast Cancer and Other Advanced Solid Tumors Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BGB-43395, by mouth</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BGB-43395, by mouth</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®), by injection or letrozole (Femara®), by mouth</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BGB-43395 is an experimental targeted therapy called a CDK4 inhibitor. It may block the enzymes CDK4 that helps cancer grow.</li> <li class="seamTextUnorderedListItem">Fulvestrant (Faslodex®) is a type of hormone therapy called a selective estrogen receptor downregulator (SERD). SERDs bind to and break down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Letrozole (Femara®) is a type of hormone therapy called an aromatase inhibitor. Aromatase inhibitors block some production of estrogen that helps cancer grow.</li> <li class="seamTextUnorderedListItem">This trial is also enrolling people with other types of cancer.</li> <li class="seamTextUnorderedListItem">Premenopausal women will also be given a drug that will put women in temporary menopause.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06120283' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://metastatictrialtalk.org/research-news/cdk-inhibitor-resistance/?utm_medium=email&utm_source=subscribers&utm_campaign=Jan2024&utm_content=Email012024' target='_blank'>Metastatic Trial Talk: Overcoming Resistance to CDK4/6 Inhibitors</a> </li></ul>

NEAREST SITE: 946 miles UCHealth - Medical Center of the Rockies Loveland,CO

NCT ID: NCT06125522

Vepdegestrant Hormone Therapy with Samuraciclib CDK7 Inhibitor for Advanced ER+ or ER Low, HER2- Breast Cancer

TACTIVE-U: AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL UMBRELLA STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF VEPDEGESTRANT (ARV-471/PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH OTHER ANTICANCER TREATMENTS IN PARTICIPANTS AGED 18 AND OLDER WITH ER+ ADVANCED OR METASTATIC BREAST CANC... Scientific Title

• <p class="seamTextPara"> You will receive the following: </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Vepdegestrant (ARV-471), by mouth, daily</li> <li class="seamTextUnorderedListItem">Samuraciclib, by mouth, daily</li></ul>
• <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">Vepdegestrant (ARV-471) is an experimental hormone therapy called a PROTAC protein degrader that breaks down estrogen receptors.</li> <li class="seamTextUnorderedListItem">Samuraciclib is an experimental targeted therapy called a CDK7 inhibitor. CDK7 inhibitors may block the CDK7 enzyme that helps cancer grow.</li></ul>
• <ul class='seamTextUnorderedList'><li class='seamTextUnorderedListItem'>View eligibility criteria and additional trial information: <a href='https://clinicaltrials.gov/ct2/show/NCT06125522' target='_blank'>ClinicalTrials.gov</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.pfizerclinicaltrials.com/nct05548127-or-nct05573555-advanced-and-metastatic-breast-cancer-trial' target='_blank'>Pfizer: Trial Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.arvinas.com/pipeline-programs/estrogen-receptor' target='_blank'>Arvinas Estrogen Receptor: ARV-471 Drug Information Page</a> </li><li class='seamTextUnorderedListItem'><a href='https://www.carricktherapeutics.com/pipeline/cdk7-inhibitor' target='_blank'>Carrick Therapeutics: Samuraciclib Drug Information Page</a> </li></ul>

NEAREST SITE: 948 miles Sarah Cannon Research Institute at HealthONE Denver,CO

NCT ID: NCT04561362

Immunotherapy and BT8009 for Metastatic Breast Cancer that Expresses Nectin-4

Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT8009 in Patients With Nectin-4 Expressing Advanced Malignancies Scientific Title

• <p class="seamTextPara"> You will be assigned to 1 of 2 groups and receive the following: </p> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 1</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BT8009, by IV, once a week, ongoing</li> </ul> <p class="seamTextPara"> <i class="seamTextEmphasis">Group 2</i> </p> <ul class="seamTextUnorderedList"> <li class="seamTextUnorderedListItem">BT8009, by IV, once a week, ongoing</li> <li class="seamTextUnorderedListItem">Nivolumab (Opdivo®), by IV, every 2 weeks, ongoing</li></ul>

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• Review Article
• Published: 17 October 2022

Systemic therapy for early-stage breast cancer: learning from the past to build the future

• Elisa Agostinetto   ORCID: orcid.org/0000-0003-0295-7511 1 ,
• Joseph Gligorov   ORCID: orcid.org/0000-0002-9900-6386 2 &
• Martine Piccart   ORCID: orcid.org/0000-0001-9068-8504 1  

Nature Reviews Clinical Oncology volume  19 ,  pages 763–774 ( 2022 ) Cite this article

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• Breast cancer
• Drug development

The treatment of breast cancer has improved dramatically over the past century, from a strictly surgical approach to a coordinated one, including local and systemic therapies. Systemic therapies for early-stage disease were initially tested against observation or placebo only in adjuvant trials. Subsequent clinical trials focusing on treatment ‘fine-tuning’ had a marked increase in cohort size, duration and costs, leading to a growing interest in the neoadjuvant setting in the past decade. Neoadjuvant trial designs have the advantages of enabling the direct evaluation of treatment effects on tumour diameter and offer unique translational research opportunities through the comparative analysis of tumour biology before, during and after treatment. Current technologies enabling the identification of better predictive biomarkers are shaping the new era of (neo)adjuvant trials. An urgent need exists to reinforce collaboration between the pharmaceutical industry and academia to share data and thus establish large databases of biomarker data coupled with patient outcomes that are easily accessible to the scientific community. In this Review, we summarize the evolution of (neo)adjuvant trials from the pre-genomic to the post-genomic era and provide critical insights into how neoadjuvant studies are currently designed, discussing the need for better end points and treatment strategies that are more personalized, including in the post-neoadjuvant setting.

Systemic therapy for patients with early-stage breast cancer has dramatically improved over the past eight decades, and the aims and designs of (neo)adjuvant clinical trials have consistently evolved.

The transition of clinical trials from the pre-genomic to the post-genomic era has been based on a deeper understanding of disease biology and a higher level of interest in the discovery of molecular markers associated with a response to treatment.

The currently adopted approach to the design of neoadjuvant trials requires a new wave of changes, with the implementation of validated end points with more robust predictive associations with survival outcomes and more personalized treatment strategies (escalation and/or de-escalation).

The evolution towards a more personalized treatment approach is leading to increasing interest in the post-neoadjuvant setting to investigate new drugs specifically in patients with high-risk disease.

Optimizing the efficiency of the search for novel biomarkers that can guide treatment tailoring requires the establishment of large, well-annotated databases of candidate biomarkers linked with clinical outcomes that are also easily accessible to the scientific community.

Early sharing of data from clinical trials should be based on joint efforts and reinforced collaboration between the pharmaceutical industry and academic entities.

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Introduction.

Breast cancer is the most common malignancy among women worldwide, with an estimated >290,000 new cases and 43,000 deaths in the USA in 2022 (ref. 1 ). These numbers are likely to be biased by the COVID-19 pandemic, which has led to reduced access to care and, consequently, to delays in diagnosis. These delays translate into a short-term lower incidence, albeit with a greater number of patients having more advanced-stage disease at diagnosis and, ultimately, increased mortality 2 . Thus, breast cancer has long been and remains a major public health problem.

Decades of research have demonstrated that breast cancer is a complex and heterogeneous disease and have provided meaningful advances in treatment options for patients, with substantial improvements in clinical outcomes over the years 3 . In this Review, we summarize the steps taken in the development of systemic therapies for patients with early-stage breast cancer, from the pre-genomic to the post-genomic era and from the identification of novel active agents to a deeper understanding of disease biology and the discovery of predictive biomarkers.

We provide critical insights into the design pitfalls of studies involving patients with early-stage breast cancer, discuss the need for better end points and propose new ways of thinking in order to address these issues. Finally, we highlight the ability of new technologies to identify novel predictive markers of efficacy that are shaping the new era of early-stage breast cancer trials.

The evolution of breast cancer treatment

The treatment of patients with breast cancer has evolved dramatically over the past century, from a strictly surgical approach to a multidisciplinary one, including radiotherapy, chemotherapy, endocrine therapy, targeted therapy and immunotherapy. This evolution has arisen from a progressively deeper understanding of the disease and from the recognition of salient, peculiar features that make it different to other cancer types 4 . Firstly, patients with node-positive disease have a higher risk of relapse in the absence of specific therapies and derive the greatest magnitude of benefit from systemic adjuvant treatments. Secondly, two-thirds of patients with breast cancer have hormone receptor (HR)-positive disease and benefit from the inhibition of oestrogen receptor (ER) signalling, using various endocrine therapies. Thirdly, breast cancer is a tremendously heterogeneous and complex disease and genetic alterations that might occur and/or drive cancer development could be useful targets for specifically designed therapies. These achievements in understanding breast cancer have been mirrored by the successful development of drugs that have been demonstrated to reduce the risk of disease relapse and death in randomized trials.

The first large-cohort studies in the adjuvant setting involving patients with early-stage breast cancer focused on the role of adjuvant chemotherapy and were either non-randomized or compared the use of chemotherapy with observation or placebo alone 5 , 6 , 7 . The findings of these seminal studies testing the role of adjuvant chemotherapy, which started in 1957 (refs. 5 , 7 , 8 ), were confirmed in subsequent studies conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) 8 and, ultimately, by large meta-analyses led by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) 6 , 9 . These analyses demonstrated meaningful reductions in the annual incidence of breast cancer recurrence and mortality (28% and 16%, respectively) with adjuvant chemotherapy regimens comprising several different agents 9 .

A first step towards a more personalized treatment approach was the evaluation of adjuvant endocrine therapy for patients with HR-positive breast cancer. In the early 1980s, seminal studies led by the Nolvadex Adjuvant Trial Organisation (NATO) 10 , 11 and the NSABP 12 provided the first data indicating clinical benefit for patients with early-stage breast cancer receiving adjuvant tamoxifen. Some years later, the EBCTCG confirmed these improvements in survival outcomes based on the pooled data of 30,000 women coming from a worldwide collaboration, where tamoxifen was associated with a highly significant reduction in the annual incidence of both disease recurrence and mortality (25% and 17%, respectively) 9 .

Finally, the advent of HER2-targeted therapies for patients with HER2-positive breast cancer marked another milestone, based on fruitful cooperation between basic research scientists and clinical investigators, in the evolution towards more personalized treatment. The HERA trial 13 demonstrated that 1 year of trastuzumab after adjuvant chemotherapy confers a significant survival benefit in these patients (10-year disease-free survival (DFS) benefit of 6–8% for patients receiving trastuzumab) 14 ; this result was confirmed in similar adjuvant trials and in an EBCTCG meta-analysis published in 2021 (ref. 15 ).

Evolution of adjuvant clinical trials

This first wave of seminal clinical trials comparing cancer therapies with observation alone or placebo was followed by a second generation of more sophisticated and refined studies comparing different interventions with each other, including different chemotherapy regimens (such as those based on anthracycline versus combinations based on anthracycline and taxane) 6 , different endocrine therapies (such as tamoxifen versus aromatase inhibitors) 16 and different targeted treatment strategies (such as single versus dual HER2 inhibition) 17 . The limited differences in magnitudes of benefit associated with these treatment modalities could not always be detected in cohorts of a suboptimal sample size. Therefore, the role of the EBCTCG in conducting periodic patient-level meta-analyses became vital in demonstrating small but significant risk reductions: the addition of a taxane to an anthracycline-based regimen in patients with node-positive breast cancer was associated with a reduction in 8-year disease recurrence of 4.6%, a reduction in 8-year breast cancer mortality of 2.8% and a reduction in 8-year all-cause mortality of 3.2%, respectively 6 . Similarly, 10-year breast cancer mortality was found to be lower with aromatase inhibitors than with tamoxifen, albeit with a modest reduction of 2.1% (12.1% vs 14.2%; P  = 0.009) 6 , 16 .

This second wave of studies led to a recognition of the need for a marked increase in trial sample size (of several thousands of patients), despite the exponentially higher costs associated with this change in approach and the continued lack of a guarantee of success. Some examples include the D-care 18 , BEATRICE 19 and ALTTO 20 studies, all of which are randomized studies with large cohorts that nonetheless failed to demonstrate statistically significant improvements for patients receiving the experimental treatments (Supplementary Table 1 ). In the ALTTO trial 20 , investigators randomly assigned 8,381 patients to 1 year of adjuvant therapy with either trastuzumab, lapatinib (a small-molecule inhibitor of both HER2 and EGFR), or both agents either in sequence or in combination. The lapatinib arm of ALTTO was closed in 2011 owing to inferiority relative to trastuzumab and, at the protocol-specified analysis cut-off, dual inhibition of HER2 with trastuzumab plus lapatinib did not improve DFS compared with trastuzumab alone. By contrast, in the APHINITY trial, dual HER2 inhibition with trastuzumab plus pertuzumab conferred a significant improvement in invasive DFS relative to trastuzumab, albeit with an improvement in 6-year event-free survival (EFS) of only 2.8% (ref. 17 ).

Notably, the magnitude of benefit derived from dual versus single HER2 inhibition was similar in the two studies (hazard ratio for DFS in ALTTO was 0.84, 97.5% CI 0.70–1.02; P  = 0.048; in APHINITY, the hazard ratio for invasive DFS was 0.81, 95% CI 0.66–1.00; P  = 0.045) 20 , 21 . The apparent failure of ALTTO and success of the same approach in APHINITY likely reflect differences in statistical assumptions 22 .

Increasing interest in neoadjuvant trials

Neoadjuvant approaches were initially developed for patients with locally advanced and/or inoperable cancers using radiotherapy, chemotherapy or a combination of the two in an attempt to render tumours operable and/or reduce tumour burden. However, data from preclinical models also suggested the potential for an additional therapeutic advantage for certain aggressive cancers as chemotherapy might decrease the replication rate of cancer cells 23 . Neoadjuvant systemic therapy was subsequently advocated as a method of increasing the feasibility of breast conservation in women considered ineligible for such an approach at diagnosis. With the landmark NSABP-B18 trial 24 demonstrating equivalent DFS and overall survival (OS) with pre-surgical versus post-surgical administration of four cycles of doxorubicin plus cyclophosphamide, trust in the preoperative administration of systemic therapy grew rapidly.

Increasing interest was also motivated by other advantages of the neoadjuvant approach, including the possibility of rapid, direct evaluation of treatment effects based on measurements of tumour diameter and the research opportunities provided by comparative investigations of tumour biology before, during and after treatment 25 (Table  1 ). Widespread adoption of the neoadjuvant approach was ultimately conferred by use of the surrogate end point of pathological complete response (pCR) as a fast and ready-to-use surrogate for long-term outcomes.

Interestingly, pCR has been supported by the FDA as a surrogate end point for the accelerated approval of new drugs tested in the neoadjuvant setting in randomized clinical trials 26 , although a ‘positive opinion’ has also been contingent on the results of clinical trials testing the same concept in another setting (such as in patients with metastatic disease). Therefore, the past 10 years have perhaps unsurprisingly witnessed exponential growth in the design and implementation of neoadjuvant trials with small cohorts that were adequately powered to detect a difference in pCR but unable to demonstrate any difference in EFS.

In 2014, a relevant association between pCR and OS was demonstrated only at the patient level in an FDA-sponsored seminal meta-analysis 27 and further evidence has since confirmed a lack of surrogacy of pCR at the trial level 28 , which raises questions regarding the role of pCR as a primary end point in ‘pivotal’ neoadjuvant trials. Surrogate end points should only be accepted as evidence supporting drug approval when these end points have been sufficiently validated and are therefore known to accurately predict the effects of a drug over time. The role of neoadjuvant trials has also evolved over time, particularly with the transition from the pre-genomic to the post-genomic era.

Entering the post-genomic era

The Human Genome Project 29 and its efforts to sequence the entire human genome were a milestone in clinical research and marked the end of the so-called pre-genomic era and the beginning of the post-genomic one. Analysis of DNA, RNA and protein sequence data is now an essential part of biomedical research 30 .

In breast cancer, these achievements have translated into a new way of thinking about neoadjuvant clinical trials. The key questions explored by neoadjuvant trials in the pre-genomic era mainly focused on the possibility of identifying active agents and predicting their success or on fine-tuning their administration schedules. Seminal research in this setting has led to milestones in today’s clinical practice such as the use of docetaxel in sequence with an anthracycline-based regimen instead of anthracycline-based chemotherapy alone 31 , the administration of weekly instead of 3-weekly paclitaxel 32 , and the superiority of adjuvant aromatase inhibitors compared to tamoxifen 33 , 34 .

All of these studies, conducted in the neoadjuvant setting, shared the peculiarity of being deemed ‘hypothesis generating’, with confirmatory results obtained subsequently in large adjuvant trials (Table 2 ). Neoadjuvant trials from the pre-genomic era had merit in that they addressed important clinical questions; however, many of these trials were characterized by disappointing results in the search for predictive biomarkers and, ultimately, a failure to identify effective biomarkers of response with the potential to enable the tailoring of treatment with taxanes 35 , 36 and/or aromatase inhibitors 33 , 37 .

Neoadjuvant trials from the post-genomic era have maintained an important role in identifying new active agents worthy of further investigation in the adjuvant setting. An example of this role is provided by dual inhibition of HER2 with pertuzumab plus trastuzumab, which was the first treatment to receive FDA accelerated approval based on pCR results alone from a relatively small ( n  = 417) neoadjuvant study (NeoSphere) 38 . The effectiveness of this approach was later confirmed in a larger cohort ( n  = 4,805) in the adjuvant setting (APHINITY) 21 , resulting in full approval for use in both settings in December 2017. We believe that the KEYNOTE-522 trial marks the beginning of a new era in the history of neoadjuvant trials: this large ( n  = 1,174), phase III study led to the approval of neoadjuvant pembrolizumab in combination with chemotherapy for patients with high-risk, early-stage triple-negative breast cancer (TNBC) in July 2021, based on significant improvements in pCR and EFS, its two co-primary end points 39 , 40 . An important lesson had been understood: a pCR improvement on its own is not a reliable surrogate of survival and should be supported by a survival end point for regulatory approval. Beyond the important role of identifying new active agents, the neoadjuvant trials of the post-genomic era have prioritized another relevant objective: the deep dissection of disease biology and the search for clinically useful molecular markers of response.

Biomarkers and disease biology

Hr-positive, her2-negative breast cancer.

Since the late 1980s, a strong preclinical rationale has supported the hypothesis that a short, preoperative course of endocrine therapy could improve outcomes in HR-positive early-stage breast cancer 41 . However, the choice of the best end point to predict patient outcomes after such therapy has been a topic of intense academic debate. Data from two small neoadjuvant studies, IMPACT 42 and Z1031 (ref. 43 ), showed that levels of the nuclear protein Ki67, assessed 2–4 weeks after starting neoadjuvant endocrine therapy, might better predict patient outcomes than Ki67 levels at baseline. In the POETIC trial 44 , 4,480 postmenopausal women with HR-positive, HER2-negative early-stage breast cancer were randomly assigned to receive either aromatase inhibitors or placebo for 14 days prior to surgery. Adjuvant treatment was permitted as per standard local practice. The POETIC trial failed to show any significant differences in treatment outcomes; importantly, however, patients with a low Ki67 level at baseline (<10%) and/or after 2 weeks of treatment had a significantly lower risk of disease recurrence compared with those with a high level at 2 weeks 44 , suggesting that ‘dynamic’ measurements of Ki67 levels could help select patients who might not need further treatment escalation (those showing substantial Ki67 suppression). For patients without a Ki67 response, current escalated treatments (such as chemotherapy) do not provide strong evidence of benefit; for example, the Z1031 trial showed no improvements in pCR for patients without a Ki67 response to short-term neoadjuvant endocrine therapy who subsequently received chemotherapy 43 . Interestingly, the WSG-ADAPT run-in trial for patients with HR-positive, HER2-negative disease 45 confirmed that combining assessments of static (genomic recurrence score) and dynamic (endocrine proliferation response defined as a Ki67 level of ≤10% following induction) biomarkers is feasible and could guide individualized therapy decisions in patients with early-stage breast cancer. Unfortunately, these results were not available at the time of the initiation of several very large adjuvant trials investigating the addition of CDK4/6 inhibitors to endocrine therapy, namely PALLAS 46 and MonarchE 47 , of which only the latter had positive results albeit in a patient population defined by a high disease burden rather than by insufficient sensitivity to endocrine therapy.

The addition of CDK4/6 inhibitors to endocrine therapy has also been explored in the neoadjuvant setting for patients with HR-positive, HER2-negative early-stage breast cancer. These trials revealed a low pCR rate (0–5%) but also demonstrated that CDK4/6 inhibitors induced more profound reductions in Ki67 levels from baseline to 2 weeks and to surgery 48 , 49 , 50 , 51 , 52 , 53 .

Next to Ki67 levels, the preoperative endocrine prognostic index (PEPI) score is another tool that allows patients to be selected as candidates for treatment escalation. The PEPI score is determined by summing the partial scores corresponding to pathological tumour and nodal stages, Ki67 levels, and ER status following neoadjuvant endocrine therapy and has been shown to predict recurrence-free survival in the context of the IMPACT trial 54 . In the ALTERNATE study 55 , 56 , women with locally advanced luminal breast cancer were randomly assigned to receive either anastrozole, fulvestrant or a combination of the two; the primary end point was endocrine-sensitive disease rate, defined as the proportion of patients with a PEPI score of 0 among all eligible patients who started neoadjuvant endocrine therapy. Of note, patients were removed from randomization if their 2-week Ki67 levels did not decline from baseline in response to endocrine therapy. Neither fulvestrant nor fulvestrant plus anastrozole significantly improved endocrine-sensitive disease rate compared with anastrozole alone 56 . Relapse-free survival data remain immature.

The search for gene expression signatures that might enable patients receiving endocrine therapy to safely avoid chemotherapy has been another area of intense research interest. Owing to the more widespread use of screening, which has modified the epidemiology of breast cancers, the question of de-escalation has become crucial. The risk of disease relapse can now be characterized by transcriptomic signatures, two of which (Oncotype-DX and MammaPrint) have proven clinical utility in the selection of patients who will have excellent outcomes on adjuvant endocrine therapy alone 57 , 58 , 59 .

The intrinsic tumour subtype is also being investigated as a potential predictive biomarker. In a retrospective, exploratory analysis of data from patients with luminal metastatic breast cancer from the MONALEESA phase III studies, all PAM50 intrinsic subtypes were associated with a consistent OS benefit with the addition of ribociclib to endocrine therapy, except for the basal-like subtype 60 . Similar data from patients with early-stage disease are not yet available.

Further complexity exists when questioning the optimal definition of ER positivity. Although 1% of cells staining ER positive on immunohistochemistry is considered the official cut-off for ER-positive breast cancer, a cut-off of 10% is often used to guide clinical decision-making, which is supported by literature reports indicating that tumours with 1–9% ER expression (so-called ER-low tumours) have similar clinical characteristics to those classed as ER-negative (<1%) 61 .

HER2-positive breast cancer

The discovery that 15–20% of breast cancers have an aggressive clinical course linked to overexpression of HER2 marked the beginning of an era of steady progress, with the registration of four HER2-targeted therapies in the early-stage disease setting 62 . Based on a growing understanding of both the HER2 signalling pathway and the mechanism of action of HER2-targeted therapies, translational research efforts have focused on identifying predictive biomarkers of response that are both directly related to HER2 itself (such as the ratio of ERBB2 copy number to CEP17 determined using FISH, polysomy, mRNA and protein expression) and go beyond HER2, namely evaluating other receptors and/or ligands (such as HER3, EGFR, EGF, IGFR), HER2 downstream signalling pathways (such as PIK3CA/PTEN or RhoA), features associated with the tumour stroma (such as tumour-infiltrating lymphocytes (TILs) or immune-related gene signatures), and other patient-specific variables (such as the presence of HER2 and/or Fcγ receptor polymorphisms). Unfortunately, none of these putative biomarkers has thus far reached clinical utility 62 , although some have generated early promising results, for example, in the WSG-ADAPT trial 63 , 64 .

Stratification based on tumour-intrinsic subtypes is another attractive strategy that could be incorporated into patient selection for treatment escalation or de-escalation. The PAM50-based HER2-enriched intrinsic subtype is associated with a higher likelihood of a pCR following neoadjuvant therapy 65 , and tools combining traditional clinical, pathological and molecular characteristics to better predict clinical outcomes in patients with early-stage HER2-positive breast cancer are currently in development 66 .

DECRESCENDO (NCT04675827) is an ongoing, single-arm, prospective trial testing de-escalation of chemotherapy for patients with HER2-positive, HR-negative and node-negative early-stage breast cancer. After neoadjuvant taxane-based chemotherapy and dual HER2 blockade, patients with a pCR will receive an additional 14 cycles of adjuvant pertuzumab plus trastuzumab but no further chemotherapy. This approach is based on the hypothesis that the HER2-enriched subtype (roughly 65–70% of the trial population) has ‘HER2-addicted’ tumours that are therefore good candidates for anthracycline omission. Nonetheless, an ambitious 3-year invasive recurrence-free survival of at least 94% will have to be demonstrated in this molecularly defined subpopulation for this trial to meet the primary end point.

Triple-negative breast cancer

TNBC has been traditionally considered a ‘targetless’ breast cancer subtype, for which chemotherapy has long been the only effective and available treatment strategy 67 . Nevertheless, advances in clinical research in the past decades have been changing the treatment landscape of TNBC, both in terms of chemotherapy options (such as the introduction of dose-dense regimens and platinum-based therapies in the neoadjuvant setting) and in terms of other therapies that are now available for patients with this tumour type, including PARP inhibitors, immune-checkpoint inhibitors and antibody–drug conjugates. Immune-checkpoint inhibitors, in particular, have revolutionized the treatment and clinical trajectory of several cancer types, and relevant efforts are being made to identify predictive biomarkers of response, including in breast cancer. PD-L1 (ref. 68 ), TILs 68 , a high tumour mutational burden (typically ≥10 mutations per megabase) 69 , mismatch repair deficiency 70 , immune gene signatures 71 and intrinsic molecular subtypes 71 are under investigation, but, so far, no biomarkers have been proven to have a clear role in predicting response to immune-checkpoint inhibitors in early-stage TNBC. A further level of complexity derives from the existence of several different diagnostic assays, scoring algorithms, intersample and intrasample heterogeneity, and differences according to the site of evaluation (metastatic versus primary lesions) 72 . Furthermore, beyond tumour characteristics, several additional factors could affect the outcomes of patients receiving immune-checkpoint inhibitors 73 , including the general characteristics of the patient (including immune function 74 , obesity 75 and/or the microbiota 76 ). Thus, the search for biomarkers capable of predicting a response to immune-checkpoint inhibitors in patients with early-stage TNBC remains a huge challenge.

A portion of the tumours that were traditionally considered to be TNBCs match the definition of the so-called HER2-low category (namely those with a HER2 immunohistochemistry score of 1+ or 2+ without detectable amplification on FISH) 77 . Robust evidence so far supports the use of the HER2-targeted antibody–drug conjugate trastuzumab deruxtecan in these patients 78 , thus underlining that the traditional distinction between these three breast cancer subtypes might be too simplistic and unhelpful in certain scenarios given that the level of expression of both HER2 and hormone receptors is not binary but rather a continuous spectrum of expression, which intrinsically limits most attempts at classification.

Time to re-think trial design?

Improving the end points of neoadjuvant trials.

The establishment of an accelerated approval pathway for drugs designed to treat serious diseases that are also unmet medical needs dates back to the early 1990s and clearly addressed the need to expedite the entire process in the best interest of patients 79 , 80 . Such pathways typically rely on improvements on one or more surrogate end points to provide an early indication of efficacy. However, considerable academic debate exists on how and when a surrogate end point can truly be considered as ‘validated’. According to certain international guidelines 81 , 82 , surrogate validation should be based on robust correlation with survival end points, both at the study level and at an individual patient level.

As explained previously, pCR is only weakly correlated with OS at the study level 28 , thus questioning the role of pCR as a valid surrogate end point. Moreover, pCR appears to lose some of its prognostic power when used to assess the efficacy of drugs that are not chemotherapies. This limitation applies to immune-checkpoint inhibitors. For example, the GeparNUEVO study 69 , 83 was a randomized, phase II study testing the addition of durvalumab to neoadjuvant chemotherapy for patients with early-stage TNBC. No significant improvement in pCR rate was observed 69 ; however, after a median follow-up duration of 43.7 months, durvalumab was associated with a significant improvement in survival outcomes (3-year OS 95.1% vs 83.1%, hazard ratio 0.26, 95% CI 0.09–0.79; P  = 0.0076) 83 . This observation might reflect that immune-checkpoint inhibitors have a different mechanism of action to that of cytotoxic agents, and, by activating an immune response against cancer cells instead of acting directly against them, they are able to produce more durable and, in some cases, delayed responses 84 , 85 , 86 . Furthermore, pCR might also not be the best end point for the evaluation of responses to neoadjuvant endocrine therapy. Compared with other breast cancer subtypes, HR-positive, HER2-negative tumours are characterized by lower pCR rates than neoadjuvant therapies and a simple distinction between pCR versus non-pCR might be not useful because few patients reach a pCR. Compared with other breast cancer subtypes, HR-positive, HER2-negative tumours are traditionally characterized by lower pCR rates than neoadjuvant therapies 87 . Thus, a dichotomous distinction between pCR and non-pCR could be an overly simplistic and inaccurate indicator of patient outcome, while the extent of residual disease could provide important additional information.

The issues with pCR justify a renewed interest in residual cancer burden (RCB). RCB is a continuous index based on the assessment of pathological measurements of the primary tumour (dimensions and cellularity fraction) and nodal metastases (number and size). Based on these parameters, the RCB index can be divided into one of four categories: RCB 0 (pCR), RCB 1, RCB 2 and RCB 3 (Fig.  1 ). The association between RCB and long-term outcomes has been robustly demonstrated in all breast cancer subtypes (HR-positive and HER2-negative, HER2-positive, and TNBC) independently of other clinical and/or pathological characteristics 88 . Evaluations of the RCB index should increasingly be adopted as a clinical end point in neoadjuvant trials involving patients with early-stage breast cancer.

Replacing pathological complete response (pCR) with a residual cancer burden (RCB) profile and event-free survival (EFS) is likely to improve the accuracy of data from neoadjuvant clinical trials as an early indicator of clinical benefit. RCB is a validated surrogate 88 , 117 of longer-term survival outcomes (such as EFS) that is also more granular than dichotomous comparisons of pCR versus non-pCR, with improved survival durations often seen for patients with more limited residual disease. Thus, post-neoadjuvant trials should increasingly explore treatment strategies directed at addressing the residual disease profile.

Considerable debate currently exists regarding the role of survival end points. In the list of surrogate end points to be used for regulatory approval purposes released by the FDA in 2018, beyond pCR, DFS, EFS, objective response rate and PFS are all permitted 89 . The initial justification for this approach comes from the desire to expedite the approval process owing to the shorter time required for assessments based on these end points compared with OS, thus allowing patients with unmet medical needs earlier access to drugs that might be effective. However, the strength of the associations of these surrogate end points with OS is not well documented. In 2020, Gyawali et al. explored the underlying evidence for these surrogate end points 90 , showing that considerable variability exists and that, in some scenarios, the association with OS is either weak or absent.

With the exponential increase in cancer drug costs in the past years, agreeing on a ‘prioritization’ list based on the real added value of such drugs is a legitimate response. This much-needed but difficult exercise has been conducted by ASCO, with the development of the ASCO Value Framework 91 , and by ESMO with the development of the ESMO Magnitude of Clinical Benefit Scale (MCBS) 92 , which values improvements in OS and/or quality of life far more heavily than improvements in ORR or extension of PFS. Interestingly, DFS has been the subject of an intense debate, leading to a reasonable consensus: living additional months or years without detectable disease has greater value than living somewhat longer with stable, non-progressive disease; thus, improvements in median DFS of sufficient magnitude are credited with high scores on the ESMO-MCBS until OS data become available, at which point a lack of OS benefit induces a one-point downgrade (ESMO-MCBS version 2.0 will soon be published 93 ). Although the scale does not include a dimension of ‘cost’, its application might help health authorities to prioritize drugs that more strongly warrant financial investment.

The post-neoadjuvant setting: a promising scenario gaining in popularity

Among the several advantages provided by the neoadjuvant approach is the possibility of selecting patients for treatment escalation or de-escalation based on their response to neoadjuvant therapy. Despite imperfect surrogacy, patients who do not have a pCR generally have worse long-term survival outcomes than those with a pCR after the completion of neoadjuvant therapy 27 . Hence, the post-neoadjuvant setting is an attractive scenario for the design of pivotal clinical trials as it involves selecting patients with high-risk residual invasive disease at surgery who might be candidates for treatment escalation. Furthermore, compared to the traditional adjuvant setting, such trials are less likely to enrol patients already cured by standard therapy (Fig.  2 ). Two systemic post-neoadjuvant treatments for patients with residual invasive disease at surgery are already approved for use in clinical practice: capecitabine for patients with TNBC, based on the results of the CREATE-X trial 94 , and trastuzumab emtansine (T-DM1) for patients with HER2-positive disease, based on the results of KATHERINE 95 .

The post-neoadjuvant setting offers the possibility of selecting patients with residual invasive disease at surgery who might benefit from additional adjuvant treatments (white text box) and also the avoidance of enrolling patients who are not likely to benefit from further therapy owing to a complete response to neoadjuvant therapy. Moreover, this approach allows translational analyses to be performed on the residual tumour material, thus enabling potential biomarkers to be identified (such as Ki67, tumour-infiltrating lymphocytes (TILs), circulating tumour DNA (ctDNA), and/or genetic and genomic alterations) (sepia text boxes), which could subsequently be validated prospectively. LVI, lymphovascular invasion; NGS, next-generation sequencing.

In the CREATE-X trial, 910 patients with early-stage, HER2-negative (HR-positive or HR-negative) breast cancer and residual disease after the completion of neoadjuvant chemotherapy were randomly assigned to either 6–8 cycles of capecitabine or to no treatment. In the overall population, post-neoadjuvant capecitabine resulted in significant improvements in invasive DFS (hazard ratio 0.70, 95% CI 0.53–0.92; P  = 0.01) and OS (hazard ratio 0.59, 95% CI 0.39–0.90; P  = 0.01), respectively, with a greater magnitude of benefit in the TNBC subgroup ( n  = 286) (hazard ratio 0.58, 95% CI 0.39–0.87 for invasive DFS, and hazard ratio 0.52, 95% CI 0.30–0.90 for OS, respectively) 94 . In the KATHERINE trial, 1,486 patients with early-stage, HER2-positive breast cancer and residual disease at surgery, after neoadjuvant chemotherapy and HER2-targeted therapy, were randomly assigned to receive either T-DM1 or trastuzumab for 14 cycles. T-DM1 was associated with a significant improvement in invasive DFS (hazard ratio 0.50, 95% CI 0.39–0.64) 95 .

In 2021, another study, OLYMPIA 96 , demonstrated a significant improvement in 3-year invasive DFS (85.9% vs 77.1%, hazard ratio 0.58, 99.5% CI 0.41–0.82; P  < 0.001) and OS (59 vs 86 events, hazard ratio 0.68, 99% CI 0.44–1.05; P  = 0.02) with olaparib in patients with high-risk, BRCA -mutated, HER2-negative early-stage breast cancer, including those previously treated in the neoadjuvant setting and who presented with residual disease at surgery.

Another attractive feature of the post-neoadjuvant setting is the possibility to perform translational analyses on residual disease and thus tailor post-surgical systemic therapy accordingly (Fig.  2 ). In other words, the evaluation of residual disease could reveal potential biomarkers (such as Ki67, TILs, RCB, and/or changes in gene expression and genetic alterations) for risk assessment and enable further fine-tuning of subsequent tailored treatments.

The post-neoadjuvant setting also features several promising treatment de-escalation scenarios. The most prominent considerations involve omitting breast and/or axillary surgery for patients without residual disease. Ongoing studies are investigating the omission of breast and/or axillary surgery after neoadjuvant systemic therapy in patients with a complete response 97 , 98 , some of them with encouraging results 99 , 100 , although this approach is currently not considered to be the standard of care.

The new era: future directions

The application of emerging technologies, including genomics, proteomics, metabolomics, pharmacogenetics and functional imaging, to the development of predictive biomarkers of efficacy is beginning to shape the new era of (neo)adjuvant clinical trials in patients with early-stage breast cancer.

Liquid biopsy

Liquid biopsy is a non-invasive method of obtaining information on tumour characteristics and thus informing on prognosis through the analysis of circulating material present in blood, including circulating tumour DNA (ctDNA) and circulating tumour cells 101 . In particular, findings from the past 10 years support the use of ctDNA sequencing as a feasible technique for use in patients with early-stage breast cancer 101 , 102 and an increasing amount of emerging data are now suggesting its clinical utility in this setting 103 , 104 . Thus, as liquid biopsy has shown promise to predict early disease relapse before imaging 103 , 104 , it could become an important tool to be implemented in study designs, to select patients requiring additional treatments and, ultimately, to guide treatment escalation or de-escalation in the post-neoadjuvant setting.

The ongoing phase II c-TRAK (NCT03145961) trial is using ctDNA mutation tracking to detect minimal residual disease and guide the use of pembrolizumab in patients with high-risk early-stage TNBC. Despite the inconclusive preliminary results presented at the San Antonio Breast Cancer Symposium 2021, c-TRAK has undoubted merit in the potential to provide proof of initial clinical utility of a ctDNA assay to guide the selective use of a systemic treatment (that is, pembrolizumab) in patients with TNBC 105 .

At the 2022 ASCO Annual Meeting, data on the role of ctDNA in the detection of late disease recurrence (>5 years from diagnosis) in women with high-risk HR-positive breast cancer were presented 106 . Of 83 evaluable patients, 10% had minimal residual disease identified via ctDNA. ctDNA was detected in all patients who had distant disease relapse within the study follow-up period ( n  = 5), with a lead time (the time from first positive ctDNA sample to clinical recurrence) of up to 37.6 months (median 12.4 months) 106 , 107 . Results from additional ongoing studies are needed to determine whether therapeutic intervention immediately after ctDNA detection can improve the clinical outcomes of these patients (such as ASPRIA (NCT04434040), PERSEVERE (NCT04849364), DARE (NCT04567420) and LEADER (NCT03285412)).

Functional imaging

Early changes in 18 F-labelled fluorodeoxyglucose ( 18 FDG) uptake observed using PET-CT during neoadjuvant therapy have been correlated with the presence or absence of pCR in several trials involving patients with early-stage breast cancer 108 , 109 . Unfortunately, none of these studies has explored the feasibility of using suboptimal standardized uptake values (SUVs) after 2–3 cycles of neoadjuvant therapy to adapt the treatment scheme and thus improve outcomes. The clinical utility of treatment de-escalation in patients with an excellent response on 18 FDG-PET appears more promising.

TBCRC026 was a phase II trial designed to investigate the correlation between 18 FDG-PET SUV corrected for lean body mass (SULmax) and pCR rate on neoadjuvant pertuzumab plus trastuzumab (without chemotherapy) in patients with ER-negative, HER2-positive early-stage breast cancer 110 . The primary objective was to demonstrate a correlation between early changes in SULmax, assessed at baseline and 15 days after the start of neoadjuvant therapy, and pCR. The primary objective of the study was not met according to the predefined statistical boundaries, although early changes in SULmax were found to predict the likelihood of a pCR, thus providing a promising strategy to guide the de-escalation of neoadjuvant therapy based on early functional imaging findings 110 in patients with tumours that appear to be highly sensitive to HER2-targeted therapy alone.

PHERGain 111 (NCT03161353) is a randomized, phase II study designed to assess early metabolic responses to neoadjuvant trastuzumab plus pertuzumab using 18 FDG-PET. In PHERGain, 18 FDG-PET is used to identify patients with HER2-positive breast cancer who are more likely to benefit from neoadjuvant dual HER2 inhibition, without chemotherapy. Interestingly, at a primary analysis, 18 FDG-PET responders (defined as a reduction of at least 40% of the maximum SUV after two cycles of treatment) had a pCR rate of 37.9% (95% CI 31.6–44.5; P  < 0.0001 compared with the historical rate) 111 . Follow-up for the survival end point (DFS) is ongoing and will ultimately provide data on the possibility of selecting patients who might be able to avoid chemotherapy.

Spatial transcriptomics and single-cell RNA sequencing

All organs of the human body, including breast tissues, are comprised of different subpopulations of cells with strictly interconnected functions. By characterizing the transcriptome of each individual cell, single-cell RNA sequencing can identify distinct subgroups of cells within the same tissue. However, this information is obtained through the isolation of cells and therefore the destruction of information regarding their spatial localization within the tissue. Spatial information is essential to understanding the interconnections existing among different cells. Hence, increasing efforts are being made to merge information coming from single-cell RNA sequencing together with spatial transcriptomics 112 . The integration of such data can further help to identify both differences and similarities between malignant and non-malignant breast tissues but also enable the dissection of intertumour and intratumour heterogeneity.

Integration and collaboration

Clinical and translational early-stage breast cancer research remains highly fragmented despite the existence of several unique initiatives such as the EBCTCG, which started in 1985, the Breast International Group founded in 1999, and the National Clinical Trial Network launched in 2014 (formerly the North America Breast Cancer Group).

The process of biomarker discovery and validation likely requires access to very large, well-annotated databases of ‘candidate biomarkers’ linked with clinical outcomes; nonetheless, no clinical trial on its own is able to achieve such a goal. For this and other reasons, the International Committee of Medical Journal Editors issued an important statement in 2016, namely that sharing data from interventional clinical trials is an ethical obligation 113 . The time has come to go one step further: after a protected period of time to enable sponsors to exploit their intellectual property rights, biomarker data collected in trials with sufficient quality control procedures should become freely accessible to the broader scientific community. The costs linked to this process will not be negligible but will be much lower than those associated with thousands of additional and increasingly sophisticated independent translational research efforts. Additionally, an increasingly active role for patient advocates in the design of future trials is sought, both as a fundamental part of academic research and to provide a ‘counterweight’ to industry-led research 114 , 115 .

The future landscape of clinical trials

Neoadjuvant and post-neoadjuvant trials are expected to have an increasing role in the evaluation of systemic therapies for patients with early-stage breast cancer (Fig.  3 ). Nonetheless, a number of methodological improvements in trial design and implementation are required. Those designing neoadjuvant strategies should aim to implement end points with more robust associations with survival outcomes and, thus far, RCB is the best candidate to replace pCR given the higher level of granularity for assessments of the extent of residual disease it provides. To optimize resources, increase efficiency and minimize the risks of exposing patients to suboptimal and sometimes toxic therapies, neoadjuvant trials should first focus on ‘signal-finding’, randomized, phase II designs involving limited numbers of patients. Results from these studies can subsequently be confirmed in larger-cohort, randomized phase III studies that are powered to demonstrate improvements in EFS. In this regard, I-SPY (NCT01042379), a US initiative, embraced this strategy many years ago by testing neoadjuvant and personalized adaptive novel agents in patients with early-stage breast cancer to determine which new drugs are most effective in particular breast cancer subtypes and to identify early predictors of treatment success. At enrolment, each new patient is included in one of the ten specific molecular subtypes; then, the I-SPY 2 randomization engine assigns each participant to a study arm, giving more weight to treatments that have proved to be more successful in that specific tumour subtype. When the predictive probabilities for an experimental agent reach a pre-specified level of either efficacy or futility, the treatment is then either declared to be successful or administration is stopped. Not surprisingly, RCB 0 (implying pCR) has been chosen as the primary end point because it enables fast turnaround and thus the rapid evaluation of new drugs. However, this design also probably explains, for reasons outlined previously, the relatively limited number of drugs declared as being ‘successful’ that have ultimately entered clinical practice in patients with early-stage disease.

Neoadjuvant trials are increasingly adopting residual cancer burden (RCB) as a surrogate end point for survival and should aim to be large ( n  = ~1,000–1,500), randomized, adequately powered for survival end points (such as event-free survival; EFS) and designed following successful phase II, ‘signal-finding’ studies. Interest in such trials is currently increasing, especially those designed to identify patients with residual disease at surgery who might benefit from treatment escalation strategies based on in-depth molecular dissection of residual invasive disease and/or the exploration of circulating tumour DNA (ctDNA) detection. Interest in traditional adjuvant strategies (without neoadjuvant treatment) is likely to decline, although such studies remain relevant to the assessment of quality-of-life (QOL) outcomes, adherence to study treatment and exploration of ‘delayed strategies’ designed to reduce the risk of late relapse (>5–10 years), especially in patients with hormone receptor-positive disease. iDFS, invasive disease-free survival.

The post-neoadjuvant setting will likely gain further popularity owing to the possibility of treatment escalation for patients with residual disease after the completion of neoadjuvant therapy. An in-depth molecular dissection of residual disease, with or without systematic screening for ctDNA detection, will help in the design of large-cohort, randomized, multi-arm, phase III trials powered to demonstrate potential improvements in invasive DFS. The pure adjuvant setting (that is, the administration of systemic treatment after surgery without patient selection based on response to a prior treatment) is expected to have a more marginal role, focusing on ways to improve treatment adherence and/or quality of life, although this approach will continue to be important for investigating ‘delayed’ treatment strategies designed to tackle the problems of tumour dormancy and/or late disease relapse in patients with HR-positive disease.

Conclusions

Breast cancer investigators have paved the way towards reinforced collaboration on two fronts: conducting pooled analyses of individual patient data from completed trials, and reducing duplication of effort in their design and implementation. After two decades of substantial research interest in small-cohort neoadjuvant trials thought to be the ideal replacement for expensive and risky adjuvant trials with larger cohorts that are ‘contaminated’ by patients with low-risk disease, a better understanding of the limitations of pCR as a surrogate end point for DFS is emerging. This observation has led to a willingness to improve the design of neoadjuvant trials, together with a growing interest in exploiting the post-neoadjuvant setting as a way to ameliorate the prognosis of patients at the highest risk. Nonetheless, the weakest aspect of this new approach remains biomarker research for improved treatment tailoring: more powerful and expensive technologies are emerging that enable the more detailed dissection of both the biology of tumours and their microenvironments; however, their use within trials with moderate cohort sizes is unlikely to provide data that support clinical utility. An accelerated, responsible, and user-friendly biomarker and clinical data-sharing process must become a high priority for the next generation of trials.

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E.A. has received fees or honoraria for consultant roles for Eli Lilly and Sandoz and support for attending medical conferences from Eli Lilly, Genetic, Istituto Gentili, Novartis and Roche, all unrelated to the submitted work. J.G. has received fees or honoraria for consultant roles for Daiichi, Eisai, Exact Science, Gilead, Lilly, Merck, Novartis, Onxeo, Pfizer, Roche Genentech and Seattle Genetics, and works in an institution that receives research grants from Eisai, Exact Science and Roche Genentech, all unrelated to the submitted work. M.P. has received fees or honoraria for consultant roles for AstraZeneca, Camel-IDS/Precirix, Frame Therapeutics, Gilead, Immunomedics, Immutep, Lilly, Menarini, MSD, NBE Therapeutics, Novartis, Odonate, Pfizer, Roche Genentech, Seagen and Seattle Genetics, is part of the scientific board at Oncolytics, and works in an institution that receives research grants from AstraZeneca, Immunomedics, Lilly, Menarini, MSD, Novartis, Pfizer, Radius, Roche Genentech, Servier and Synthon, all unrelated to the submitted work.

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Agostinetto, E., Gligorov, J. & Piccart, M. Systemic therapy for early-stage breast cancer: learning from the past to build the future. Nat Rev Clin Oncol 19 , 763–774 (2022). https://doi.org/10.1038/s41571-022-00687-1

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NIH study advances personalized immunotherapy for metastatic breast cancer

An experimental form of immunotherapy that uses an individual’s own tumor-fighting immune cells could potentially be used to treat people with metastatic breast cancer, according to results from an ongoing clinical trial led by researchers at the National Cancer Institute’s (NCI) Center for Cancer Research, part of the National Institutes of Health. Many people with metastatic breast cancer can mount an immune reaction against their tumors, the study found, a prerequisite for this type of immunotherapy, which relies on what are called tumor-infiltrating lymphocytes (TILs).

In a clinical trial of 42 women with metastatic breast cancer, 28 (or 67%) generated an immune reaction against their cancer. The approach was used to treat six women, half of whom experienced measurable tumor shrinkage. Results from the trial appeared Feb. 1, 2022, in the Journal of Clinical Oncology .

“It’s popular dogma that hormone receptor–positive breast cancers are not capable of provoking an immune response and are not susceptible to immunotherapy,” said study leader Steven A. Rosenberg, M.D., Ph.D., chief of the Surgery Branch in NCI’s Center for Cancer Research. “The findings suggest that this form of immunotherapy can be used to treat some people with metastatic breast cancer who have exhausted all other treatment options.”

Immunotherapy is a treatment that helps a person’s own immune system fight cancer. However, most available immunotherapies, such as immune checkpoint inhibitors, have shown limited effectiveness against hormone receptor–positive breast cancers, which are the majority of breast cancers.

The immunotherapy approach used in the trial was pioneered in the late 1980s by Dr. Rosenberg and his colleagues at NCI. It relies on TILs, T cells that are found in and around the tumor.

TILs can target tumor cells that have specific proteins on their surface, called neoantigens, that the immune cells recognize. Neoantigens are produced when mutations occur in tumor DNA. Other forms of immunotherapy have been found to be effective in treating cancers, such as melanoma, that have many mutations, and therefore many neoantigens. Its effectiveness in cancers that have fewer neoantigens, such as breast cancer, however, has been less clear. 

The results of the new study come from an ongoing phase 2 clinical trial being carried out by Dr. Rosenberg and his colleagues. This trial was designed to see if the immunotherapy approach could lead to tumor regressions in people with metastatic epithelial cancers, including breast cancer. In 2018, the researchers showed that one woman with metastatic breast cancer who was treated in this trial had complete tumor shrinkage, known as a complete response.

In the trial, the researchers used whole-genome sequencing to identify mutations in tumor samples from 42 women with metastatic breast cancer whose cancers had progressed despite all other treatments. The researchers then isolated TILs from the tumor samples and, in lab tests, tested their reactivity against neoantigens produced by the different mutations in the tumor.

Twenty-eight women had TILs that recognized at least one neoantigen. Nearly all the neoantigens identified were unique to each patient.

“It’s fascinating that the Achilles’ heel of these cancers can potentially be the very gene mutations that caused the cancer,” said Dr. Rosenberg. “Since that 2018 study, we now have information on 42 patients, showing that the majority give rise to immune reactions.”

For the six women treated, the researchers took the reactive TILs and grew them to large numbers in the lab. They then returned the immune cells to each patient via intravenous infusion. All the patients were also given four doses of the immune checkpoint inhibitor pembrolizumab (Keytruda) before the infusion to prevent the newly introduced T cells from becoming inactivated.

After the treatment, tumors shrank in three of the six women. One is the original woman reported in the 2018 study, who remains cancer free to this day. The other two women had tumor shrinkage of 52% and 69% after six months and 10 months, respectively. However, some disease returned and was surgically removed. Those women now have no evidence of cancer approximately five years and 3.5 years, respectively, after their TIL treatment.

The researchers acknowledged that the use of pembrolizumab, which has been approved for some early-stage breast cancers, may raise uncertainties about its influence on the outcome of TIL therapy. However, they said, treatment with such checkpoint inhibitors alone has not led to sustained tumor shrinkage in people with hormone receptor–positive metastatic breast cancer.

Dr. Rosenberg said that with the anticipated opening early this year of NCI’s new building devoted to cell-based therapies, he and his colleagues can begin treating more individuals with metastatic breast cancer as part of the ongoing clinical trial. He noted that this new immunotherapy approach could potentially be used for people with other types of cancer as well.

“We’re using a patient’s own lymphocytes as a drug to treat the cancer by targeting the unique mutations in that cancer,” he said. “This is a highly personalized treatment.”

About the Center for Cancer Research (CCR): CCR comprises nearly 250 teams conducting basic, translational, and clinical research in the NCI intramural program — an environment supporting innovative science aimed at improving human health. CCR’s clinical program is housed at the NIH Clinical Center — the world’s largest hospital dedicated to clinical research. For more information about CCR and its programs, visit ccr.cancer.gov .

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• Open access
• Published: 21 August 2024

The DNA repair pathway as a therapeutic target to synergize with trastuzumab deruxtecan in HER2-targeted antibody–drug conjugate–resistant HER2-overexpressing breast cancer

• Jangsoon Lee   ORCID: orcid.org/0000-0002-6862-5686 1 , 9 , 10   na1 ,
• Kumiko Kida 1   na1   nAff11 ,
• Jiwon Koh 2 , 3 ,
• Huey Liu 1 ,
• Ganiraju C. Manyam 4 ,
• Young Jin Gi 1 , 9 ,
• Dileep R. Rampa 9 ,
• Asha S. Multani 5 ,
• Jing Wang 5 ,
• Gitanjali Jayachandran 6 ,
• Dae-Won Lee 2 , 8 ,
• James M. Reuben 6 ,
• Aysegul Sahin 7 ,
• Lei Huo 7 ,
• Debu Tripathy 1 ,
• Seock-Ah Im 2 , 8 &
• Naoto T. Ueno 1 , 9  

Journal of Experimental & Clinical Cancer Research volume  43 , Article number:  236 ( 2024 ) Cite this article

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Anti-HER2 therapies, including the HER2 antibody–drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have led to improved survival outcomes in patients with HER2-overexpressing (HER2+) metastatic breast cancer. However, intrinsic or acquired resistance to anti-HER2–based therapies remains a clinical challenge in these patients, as there is no standard of care following disease progression. The purpose of this study was to elucidate the mechanisms of resistance to T-DM1 and T-DXd in HER2+ BC patients and preclinical models and identify targets whose inhibition enhances the antitumor activity of T-DXd in HER2-directed ADC-resistant HER2+ breast cancer in vitro and in vivo.

Targeted DNA and whole transcriptome sequencing were performed in breast cancer patient tissue samples to investigate genetic aberrations that arose after anti-HER2 therapy. We generated T-DM1 and T-DXd–resistant HER2+ breast cancer cell lines. To elucidate their resistance mechanisms and to identify potential synergistic kinase targets for enhancing the efficacy of T-DXd, we used fluorescence in situ hybridization, droplet digital PCR, Western blotting, whole-genome sequencing, cDNA microarray, and synthetic lethal kinome RNA interference screening. In addition, cell viability, colony formation, and xenograft assays were used to determine the synergistic antitumor effect of T-DXd combinations.

We found reduced HER2 expression in patients and amplified DNA repair–related genes in patients after anti-HER2 therapy. Reduced ERBB2 gene amplification in HER2-directed ADC–resistant HER2+ breast cancer cell lines was through DNA damage and epigenetic mechanisms. In HER2-directed ADC–resistant HER2+ breast cancer cell lines, our non-biased RNA interference screening identified the DNA repair pathway as a potential target within the canonical pathways to enhance the efficacy of T-DXd. We validated that the combination of T-DXd with ataxia telangiectasia and Rad3-related inhibitor, elimusertib, led to significant breast cancer cell death in vitro ( P  < 0.01) and in vivo ( P  < 0.01) compared to single agents.

Conclusions

The DNA repair pathways contribute to HER2-directed ADC resistance. Our data justify exploring the combination treatment of T-DXd with DNA repair–targeting drugs to treat HER2-directed ADC–resistant HER2+ breast cancer in clinical trials.

Introduction

Breast cancer (BC) is a heterogeneous disease that is classified into three subtypes that guide treatment: hormone receptor-positive, human epidermal growth factor receptor 2 positive (HER2+), and triple-negative. HER2, a member of the ErbB receptor tyrosine kinase family and an oncogene, is amplified or overexpressed in 15%-30% of BC cases [ 1 ] and activates oncogenic signaling pathways such as proliferation, angiogenesis, and metastasis by homodimerization or heterodimerization with other ErbB receptors, including EGFR, HER3, and HER4 [ 2 ]. HER2 overexpression is associated with higher rates of disease recurrence, brain metastasis, and mortality [ 3 ].

The HER2 oncogene is a well-defined BC biomarker for targeted therapies [ 4 ]. The humanized monoclonal antibody trastuzumab was the first targeted therapy for the HER2 protein, targeting its extracellular domain; as an advanced and adjuvant treatment with chemotherapy for patients with HER2+ BC, trastuzumab has been associated with a significant survival benefit [ 5 ]. Subsequent preclinical studies have led to other humanized monoclonal antibodies (e.g., pertuzumab, margetuximab) and small-molecule kinase inhibitors (e.g., lapatinib, neratinib, and tucatinib) targeting the intracellular kinase domain of HER2. Since anti-HER2 therapy enhances the therapeutic efficacy of chemotherapy, the antibody–drug conjugate (ADC) class of drugs was developed to maximize the cytotoxic effect of anti-HER2 therapy and chemotherapy via endocytosis selectively in HER2+ tumor cells [ 6 ]. Two such ADCs, ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd, also called DS8201a), were approved by the U.S. Food and Drug Administration (FDA) to treat HER2+ metastatic BC and unresectable or metastatic HER2-low BC. T-DXd is composed of an anti-HER2 antibody with the same amino acid sequence as trastuzumab, a cleavable tetrapeptide linker, and a membrane-permeable topoisomerase I inhibitor that is an exatecan (DX-8951f) derivative [ 7 ]. T-DXd showed enhanced tumor cell killing in a T-DM1–resistant HER2+ xenograft model and a low-HER2-expressing BC model [ 8 ]. In clinical trials of patients with HER2+ metastatic BC, T-DXd showed durable antitumor activity and progression-free survival in a T-DM1–pretreated population (DESTINY-Breast01 and DESTINY-Breast02 trials) [ 9 , 10 ], and had better therapeutic efficacy than T-DM1 (DESTINY-Breast03 trial) [ 11 ]. T-DXd also resulted in significantly longer progression-free and overall survival duration than untargeted chemotherapy in patients with HER2-low metastatic BC (DESTINY-Breast04 trial) [ 12 ].

Despite the clinical benefits of HER2-directed ADC, BC often develops resistance to treatment. Understanding the mechanisms of innate or acquired resistance to HER2-directed ADC therapy and identifying potential novel therapeutic targets to overcome this resistance is important to improve outcomes in patients with metastatic HER2+ BC. In this study, we investigated mechanisms of resistance to T-DM1 and T-DXd in HER2+ BC patients and preclinical models and identified potential targets whose inhibition enhances the antitumor activity of T-DXd in HER2-directed ADC-resistant HER2+ BC in vitro and in vivo.

Materials & methods

Detailed information regarding the sulforhodamine B cell proliferation assay, high-throughput RNA interference (RNAi) screening, the whole-genome sequencing analysis, karyotyping by G-banding and the genomic instability analysis, the fluorescence in situ hybridization analysis, the microarray analysis, the droplet digital PCR assay, and Western blotting is included in the electronic Supplementary Material.

Patient data analysis after anti-HER2 and T-DM1 treatment

Ten patients with HER2+ metastatic BC that had progressed during treatment with T-DM1 and/or dual treatment with pertuzumab and trastuzumab were prospectively enrolled at MD Anderson (institutional review board [IRB] No: PA15-0499). All patients underwent biopsies from a primary or metastatic site before treatment with T-DM1 and/or pertuzumab and trastuzumab and after the development of clinical resistance to treatment. HER2 expression levels before and after therapy were compared using immunohistochemistry staining (IHC) and/or fluorescence in situ hybridization. Targeted next-generation sequencing was performed using the FoundationOne CDx assay (Foundation Medicine, Inc.) to identify gene alterations. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) software (V11, https://string-db.org/ ) was used for the functional enrichment analysis to find canonical pathways using gene alteration information. Patient characteristics are shown in Sup. Table 1 and details of clinicopathological features and treatments of patients are shown in Sup. Table 2.

Targeted DNA sequencing on human BC samples before and after T-DXd treatment

Tissue samples from 16 patients at Seoul National University Hospital (SNUH), including pre- and post-T-DXd treatment metastatic BC samples from three patients, were used in a separate genomic analysis (SNUH IRB No. 2310–165-1480). Targeted DNA sequencing was performed using formalin-fixed paraffin-embedded (FFPE) samples, and the results were aligned to the reference genome (GRCh37/hg19) using Burrows-Wheeler Aligner (version 0.7.17) [ 13 ], followed by processing through the Genome Analysis Tool Kit (version 4.0.2.1) [ 14 ]. Clinicopathological features of patients treated with T-DXd shown in Sup. Table 3. A list of genes selected for targeted DNA sequencing is summarized in Sup. Table 4. We developed an in-house pipeline to call SNVs/indels by modifying SNVer (version 0.5.3) [ 15 ] and LoFreq (version 2.1.2) [ 16 ]. DELLY and Manta were used to detect translocations [ 17 , 18 ]. For copy number variation (CNV) estimation, a panel of normal samples was established by sequencing non-neoplastic samples. CNV calls were made through an in-house developed process based on CNVKit [ 19 ]; amplifications were called when copy number estimates reached ≥ six copies, and homozygous deletions were called at zero copies. ANNOVAR and SnpEff (version 4.3) were used for annotation [ 20 , 21 ]. All CNV and structural variations were manually reviewed with the Integrative Genomics Viewer (IGV) [ 22 ]. To filter out possible germline variants, those with an allele frequency of more than 0.1% in the Genome Aggregation Consortium (gnomAD) East Asian database [ 23 ], Korean Reference Genome Database [ 24 ], and Korean Variant Archive were discarded [ 25 ].

RNA-seq and gene set enrichment analysis

RNA-seq was performed on six paired samples from SNUH, which included three samples obtained before the T-DXd treatment and three obtained at the time of disease progression after T-DXd. Sequencing libraries were prepared using SureSelect RNA Direct_Human (Agilent Technologies) and sequenced on the Illumina NovaSeq 6000 (Macrogen, Seoul, Republic of Korea) using the paired-end 2 × 100-bp option. After quality assessment of raw FASTQ files using FastQC (v.0.11.7), adapter sequences in sequencing reads were trimmed using Trimmomatic (v.0.38) [ 26 ]. Reads were aligned using HISAT2 (v.2.1.0) [ 27 ] and assembled and quantified using StringTie (v.2.1.3b) [ 28 ] as read counts.

The raw read counts were normalized using DESeq2 [ 29 ], and the normalized read counts were used as inputs in the gene set enrichment analysis (GSEA) [ 30 ]. GSEA was performed between pre- and post-TDX-d samples, and the analysis was performed by gene set permutation mode due to the small sample size [ 31 ]. Gene sets from the Molecular Signatures Database (MSigDB, http://software.broadinstitute.org/gsea/msigdb ) [ 32 ] were used. A cut-off false discovery rate (FDR) q-value of ≤ 0.25 was used to define significant enrichment.

Cell lines and reagents

HCC1954, SKBR3, BT474, HCC1419, and MDA-MB-231 BC cells were purchased from the American Type Culture Collection (Manassas, VA, USA). SUM190 BC cells were purchased from Asterand Bioscience (Detroit, MI, USA). KPL4 BC cells were provided by Kawasaki Medical School (Okayama, Japan). HCC1954, SKBR3, BT474, and HCC1419 cells were maintained in Roswell Park Memorial Institute 1640 medium (Sigma-Aldrich, St. Louis, MO, USA). MDA-MB-231 cells were maintained in Dulbecco’s modified Eagle’s medium/F-12 medium (Sigma-Aldrich). SUM190 and KPL4 cells were maintained in Ham’s F-12 medium (Sigma-Aldrich) supplemented with 5 µg/mL of insulin (Thermo Fisher Scientific Inc., Waltham, MA, USA), and 1 µg/mL of hydrocortisone (Sigma-Aldrich). All media were supplemented with 10% fetal bovine serum (GenDEPOT, Katy, TX, USA) and 1% antibiotic/antimycotic (Sigma-Aldrich). All cell lines were validated by DNA typing at the MD Anderson Characterized Cell Line Core and confirmed to be free of Mycoplasma using the MycoAlert Mycoplasma Detection Kit (Lonza, Morristown, NJ, USA).

T-DM1-resistant (TDM1R) or T-DXd–resistant (TDXdR) HER2+ BC cell lines were established by a continuous treatment/recovery cycle with HER2-directed ADC. In brief, 1 × 10 5  cells were seeded into a 100-mm cell culture dish and incubated overnight. The next day, the cells were treated with T-DM1 or T-DXd at the IC 80 concentration, as determined by a sulforhodamine B cell proliferation assay. After 3–5 days of incubation, the culture media was replaced with fresh media without HER2-directed ADC until cells recovered about 30%-50% cell confluency. The treatment/recovery cycle was repeated with a 10%-25% increased HER2-directed ADC concentration until BC cells were resistant to at least 2 µg/mL of HER2-directed ADC.

Ataxia telangiectasia and Rad3-related inhibitor elimusertib (also known as BAY 1895344), abemaciclib, AZD1775, BYL719, olaparib, and TAS-119 were purchased from MedChemExpress (Monmouth Junction, NJ, USA). T-DM1 was purchased from the MD Anderson Pharmacy division. T-DXd and DXd were provided by Daiichi Sankyo Co., Ltd. (Tokyo, Japan).

Xenograft studies

For the tumorigenicity studies, 315 of 4- to 6-week-old female athymic nude mice (#002019, Jackson Laboratory, Bar Harbor, ME, USA) were housed under pathogen-free conditions and treated per National Institutes of Health guidelines. To establish TDM1R and TDXdR BC cell line xenografts, cell suspensions (4 × 10 6 cells/100 µL) in 50% Matrigel were injected into one site in each mouse's abdominal mammary fat pad. When tumors were approximately 100–250 mm 3 , mice were randomly distributed into four groups ( n  = 10–15 mice per group) to achieve similar average tumor volumes (200–250 mm 3 ) and standard deviation across the groups. T-DXd (10 mg/kg) was administered one time on Day 0 via intravenous injection as previously described [ 7 , 8 ], and elimusertib was administered twice a day in a cycle of 3 days on and 4 days off via oral gavage in 40% propylene glycol 400 (Lab Alley, Austin, TX, USA) plus 10% ethanol. Tumor volume [ V  = 0.5 × ( L  ×  W 2 )] was measured by caliper and body weight was measured twice weekly. Following euthanasia using carbon dioxide inhalation, tumor samples were collected, and animal remains were handled in accordance with institutional biohazard waste disposal protocols.

IHC staining

Xenograft tumor tissues were fixed in 10% neutral-buffered formalin and embedded in paraffin. The Sects. (5-μm thick) were deparaffinized in xylene for 2 min three times, rehydrated in graded alcohols for 1 min, and washed in distilled water. IHC staining was performed using VECTASTAIN® Elite® ABC-HRP Kit (PK-7200, Newark, CA, USA) for manual staining or the Leica BOND-RX m automated IHC staining system (Leica Biosystems, Wetzlar, Germany) through the MD Anderson Department of Veterinary Medicine and Surgery Histology Core. The Leica Refine polymer kit (#DS-9800) was used for detection in IHC. The slides were then incubated with the following antibodies: anti–Ki-67 (#RM-9106, 1:100, Thermo Fisher Scientific), anti-HER2 (#APA342AA, Biocare Medical, Pacheco, CA, USA), anti–phospho-ATR (#2933, 1:200, Cell Signaling Technology, Danvers, MA, USA), or anti–cleaved poly(ADP-ribose) polymerase (PARP, #5625, 1:100, Cell Signaling Technology). Immunostained slides were scanned using an Aperio AT2 slide scanner (Leica Biosystems) and captured at 20 × magnification using Aperio ImageScope software (Leica Biosystems). HER2 expression was measured on both membrane and cytosol. pH2AX, pATR, or Ki-67 was evaluated on nucleus expression only.

Statistical analysis

The cell proliferation rate was summarized with descriptive statistics (mean, median, and quartiles) and box plots for each treatment group. A two-tailed unpaired Student’s  t -test was used for statistical analysis using GraphPad Prism (version 9, GraphPad Software, Boston, MA, USA). For the evaluation of xenograft assays, treatment groups were compared at the indicated time points using multiple t -test analysis of multiple comparisons testing using GraphPad Prism. P  ≤ 0.05 was considered significant.

ERBB2 gene reduction and alteration of DNA repair were observed after receipt of HER2-targeted therapies in patients with HER2+ BC

We analyzed paired pre- and post-treatment samples from 10 patients who underwent anti-HER2 treatment and chemotherapy for metastatic BC and experienced disease progression during treatment. Of these, 5 patients received T-DM1. HER2 expression was reduced in the post-treatment biopsy in 4 of the 10 patients, including 3 of the 5 patients who received T-DM1 therapy after trastuzumab and pertuzumab combination therapy (Fig.  1 A). The reduction in HER2 expression in these patients was accompanied by the loss of ERBB2 amplification. At disease progression after T-DM1, 3 of 5 patients (60%) had lost ERBB2 amplification. In contrast, in patients treated with trastuzumab and pertuzumab alone, only 1 of the 5 (20%) had lost HER2 amplification.

DNA repair pathways are activated after HER2-targetd drug treatment in patients with HER2+ BC. A Targeted WGS was performed on 10 paired patient samples after treatment with trastuzumab/pertuzumab or T-DM1. The table shows gene amplification or variation after treatment. B The gene list was analyzed using STRING software (version 11.0) to show similar categories by functions of genes. In the context of the STRING analysis, k-means clustering was applied to identify groups of genes with similar behavior. Each color indicates co-regulated gene modules related to specific canonical signaling pathways. C Targeted DNA sequencing was performed to identify gene alteration profiling from five pairs before and after T-DXd treatment and six after T-DXd treatment in BC patients tissue samples. Genomic DNA was collected from FFPE tissue samples. D Gene expression analysis in three pairs before and after T-DXd treatment in HER2+ BC patients tissue samples. Total RNA was collected from FFPE tissue slides, and an RNA-seq analysis was conducted

In patients with reduced HER2 expression, heterogeneity across specimen sites was observed. In three cases, HER2 expression was negative in some specimens, even in the pre-treatment biopsy—for example, HER2 was expressed in the primary BC tumor but not in the lymph nodes. In such cases, HER2 status was more likely to change after treatment. In contrast, in six cases, regardless of multiple biopsies, HER2 was consistently positive.

To explore the mechanism of HER2 loss and the development of resistance to anti-HER2 treatment, we analyzed genomic changes between the paired pre- and post-treatment samples, using the STRING database to identify protein–protein interactions. A pathway analysis showed multiple gene alterations after anti-HER2 treatment (Fig.  1 B). In particular, genes related to the DNA repair pathway were amplified, including TOP2A, RAD21, RAD52, and MCL1. Of note, TOP2A, RAD21, and MCL1 were simultaneously upregulated in several cases. MCL1 amplification was observed in the three cases, including two cases with unchanged HER2 expression and one case with reduced expression. TOP2A amplification was observed in two cases with unchanged HER2 expression.

Genetic alterations and gene expression profiles revealed upregulation of DNA repair pathway in patients with HER2+ BC after receipt of T-DXd

The most common genetic alterations in human BC samples from SNUH were TP53 mutations (82.3%), ERBB2 amplifications (56.3%), CDK12 amplifications (43.8%), MYC amplifications (37.5%), and CDKN2A/2B copy number loss (37.5%) (Fig.  1 C, Sup. Table 5, and Sup. Table 6). Some interesting features were noted when comparing the paired samples from the same patients (Sup. Table 5). While PT02, PT03, and PT04 had similar mutational profiles regardless of treatment history, we observed differences between pre- and post-T-DXd samples in PT01 and PT05. PT01 lost the CD274 splicing mutation and CDK12 truncation mutation during treatment. In contrast, PT01 gained the GNAS R201H hotspot activating mutation. PT05 harbored a MAP3K1 nonsense mutation and AURKA amplification, which were not detectable after T-DXd treatment. However, the TP53 R273C mutation emerged after T-DXd treatment, along with pathogenic mutations in ARID1A and FGFR4 . In addition, copy number loss of JAK2/CD274/PDCD1LG2 was noted in PT05_Post as well as amplifications of CCND1/FGF19 .

Copy number losses of many DNA repair–related genes, including BRCA2 , RAD51B , ATM , and MRE11, were also observed in PT05_Post, although their exact roles would require additional study. Interestingly, when focusing on the ERBB2 copy numbers in the paired samples, we observed a trend of decreasing ERBB2 copy numbers in post-T-DXd samples compared to pre-T-DXd samples; however, cautions should be taken for this trend might have stemmed from the technical limitations of targeted sequencing or the discrepancy in tumor purity in each sample. Taken together, we found that the overall mutational landscapes of pre-T-DXd and post-T-DXd human samples are largely similar; however, certain discrepancies do exist that necessitate additional study in a larger cohort of T-DXd-treated population.

RNA-seq was conducted on the paired samples from PT01, PT02, and PT03. To elucidate the enriched cellular pathways in pre- and post-T-DXd treatment BC samples, we performed GSEA on three paired samples. Most importantly, MYC_TARGETS_V2 (normalized enrichment score [NES] = 2.144; FDR q-value < 0.001), MTORC1_SIGNALING (NES = 2.134; FDR q-value = 0.002), and DNA_REPAIR (NES = 1.625; FDR q-value = 0.002) were significantly enriched in post-T-DXd samples (Fig.  1 D, Sup. Table 7).

HER2-directed ADC-resistant HER2+ BC cell lines show reduced ERBB2 gene and HER2 protein expression

To better understand the mechanisms of the molecular changes in patient samples after the development of resistance to HER2-directed ADC therapies, we established HER2-directed ADC–resistant HER2+ BC cell lines. First, we determined the ERBB2 gene copy number in five HER2+ BC cell lines: SKBR3, BT474, HCC1954, SUM190, and HCC1419. We confirmed that all tested HER2+ BC cell lines were ERBB2 gene amplified ( ERBB2 gene copy number: > 10) compared to the triple-negative BC cell line MDA-MB-231 that was known to HER2-negative cell line ( ERBB2 gene copy number: 1.01) (Fig. S1A). Next, we evaluated the sensitivity of HER2+ BC cell lines to HER2-ADC and observed a dose-dependent response to T-DM1 or T-DXd treatment in the 5-day short-term treatment condition (Fig. S1B).

On the basis of proliferation data, we selected SUM190 (which had the highest HER2 copy number) and HCC1954 (which had the lowest) (Fig. S1A). Before generating HER2-directed ADC-resistant cell lines, we first tested the antitumor effects of T-DM1 and T-DXd in xenograft models and confirmed that single-agent treatment led to tumor shrinkage in both SUM190 (-66.84% GI and -25.56% GI respectively, P  < 0.001) and HCC1954 (-18.60% GI and -22.82% GI respectively, P  < 0.05) xenografts compared to in vehicle control (Fig. S1C).

To generate HER2-directed ADC–resistant BC cell lines, we treated SUM190 and HCC1954 parent cells with T-DM1 or T-DXd at the 80% inhibitory concentration (IC 80 ) for 3–5 days and then replaced the culture media with fresh complete media until cells recovered at a normal growth rate. This treatment/recovery cycle was repeated for about 6–12 months (Fig.  2 A). We confirmed that no TDM1R and TDXdR HER2+ BC cell lines showed growth inhibition when treated with 2 µg/mL of T-DM1 or T-DXd while parent BC cell lines showed over 90% cell death with the same treatment (Fig.  2 B; TDM1R and TDXdR indicate resistance to TDM1 and T-DXd, respectively). We also confirmed that both SUM190-TDXdR and HCC1954-TDXdR cell lines did not show growth inhibition when treated with the T-DXd payload, DXd( P  < 0.0001, Fig.  2 C) but did show growth inhibition in TDM1R-resistant cell lines ( P  < 0.01, Fig.  2 C).

Anti-HER2 antibody–drug conjugate (HER2-directed ADC)–resistant HER2+ BC cell line generation. A TDM1R and TDXdR cell lines generated by continuous treatment/recovery cycle with HER2-directed ADC. SUM190 (1 million) and HCC1954 (500,000) cells were added to the 100-mm culture dish. The next day, cells were treated with T-DM1 or T-DXd at the 80% inhibitory concentration (IC 80 ) for 3–5 days and then replaced with fresh complete media until cells recovered at a normal growth rate. This treatment/recovery cycle was repeated for about 6–12 months. B Clonogenic assay. Parent TDM1R and TDXdR cell lines were treated with 2 µg/ml of T-DM1 or T-DXd for 14 days, and viability was measured by an SRB staining assay. Experiments were repeated three times independently. Data were collected from three biological replicates. C Antiproliferation effect of T-DXd payload and DXd in parent and TDM1R and TDXdR cell lines. Cells were treated with DXd for 14 days, and viability was measured by the SRB staining assay. Data were collected from three biological replicates. D T-DXd significantly reduces tumor growth in SUM190-TDM1R ( n  = 12 per group) and HCC1954-TDM1R ( n  = 9 per group) xenograft models. A multiple t -test comparison was used to compare tumor size between the control and treatment groups. E TDM1R and TDXdR cell lines showed reduced HER2 expression. The ImageJ program was used to measure intensity. Western blotting. F FACS analysis. TDM1R and TDXdR cell lines showed reduced cell-surface HER2 expression. Cells were maintained without drug for 7 days and collected to measure HER2 expression on the cell surface with anti-HER2-PE. Three biological replicates showed similar results. G Droplet digital PCR assay. CNV indicates copy number variation. TDM1R and TDXdR cell lines showed a reduced ERBB2 gene copy number. Each box shows mean with standard deviation; **,  P  < 0.01; ***,  P  < 0.001, ****,  P  < 0.0001, n.s. not significant. Data were collected from three biological replicates

To confirm the antitumor effect of T-DXd in TDM1R BC models, we conducted a xenograft assay and confirmed that T-DXd significantly reduced tumor growth in both SUM190-TDM1R (70.5% GI) and HCC1954-TDM1R (-85.9% GI) xenograft models (Fig.  2 D, P < 0.01). Next, we determined the HER2 expression levels in TDM1R and TDXdR BC cell lines using Western blotting and fluorescence-activated cell sorting (FACS) analysis. Both T-DM1- and T-DXd-resistant HER2+ BC cell lines had reduced total HER2 protein and cell surface HER2 expression levels (Fig.  2 E and F). To determine whether reduced HER2 protein expression in TDM1R and TDXdR BC cell lines was due to downregulation of gene expression levels, we performed a droplet digital PCR assay and observed reduction of ERBB2 gene copy numbers in all TDM1R and TDXdR BC cell lines (SUM190-TDM1R and SUM190-TDXdR: > 80% reduction, P  < 0.0001, SUM190-TDM1R and SUM190-TDXdR: > 40% reduction, P  < 0.001) compared to in parent cell lines (Fig.  2 G).

Genetic alterations cause downregulation of HER2 gene expression

TDM1R and TDXdR BC cell lines showed reduced HER2 gene copy number and protein levels (Fig.  2 ). We validated the HER2 gene copy number data by fluorescence in situ hybridization analysis using the T-DM1R and TDXdR BC cell lines. As shown in Fig.  3 A, parent SUM190 and HCC1954 cell lines showed HER2 gene amplification (HER2/CER17 ratio: 3.497 and 3.002, respectively), but SUM190-TDM1R (0.7004), SUM190-TDXdR (0.1352), HCC1954-TDM1R (0.6826), and HCC1954-TDXdR (1.851) cell lines showed less HER2 gene amplification in both metaphase and interphase than did parent cells ( P  < 0.0001). To elucidate how HER2-directed ADC reduces HER2 gene expression in HER2+ BC cell lines, we first assessed chromosome instability, which is closely related to cancer development, gain or loss of gene expression, and therapeutic resistance [ 33 , 34 ]. We analyzed chromosomes in 35 metaphase cells from each parent cell line and TDM1R and TDXdR BC cell lines. We observed chromosomal aberrations in both parent and TDM1R and TDXdR BC cell lines; however, these aberrations were not increased in TDM1R and TDXdR BC cell lines compared to in parent cells (Fig. S2A). Interestingly, the SUM190-TDXdR cell line showed truncation of the HER2 gene-amplified region (Fig. S2B). On the basis of this observation, we analyzed the gene copy number ratios between the parent and TDM1R and TDXdR BC cell lines of the gene copy numbers of ERBB2 , MIEN1 , MIR4728 , and PGAP3 near the HER2 gene location, using whole-genome sequencing data. In the SUM190-TDM1R and SUM190-TDXdR cell lines, the gene copy numbers of ERBB2, MIEN1, MIR4728, and PGAP3 were reduced by at least 50% compared to the SUM190 parent cell line. We observed similar reductions in copy numbers of these genes in the HCC1954 cell lines (Fig.  3 B). Interestingly, KPL4, which is relatively resistant to T-DXd compared to SUM190 (> tenfold higher than IC 50 of SUM190) and chronically exposed to T-DXd with 2 µg/ml (KPL4-TDXdR), retained HER2 gene expression, but the T-DM1-resistant KPL4 cell line showed reduced HER2 gene copy numbers (Fig. S2C). Altogether, these data suggest that chronic exposure to the HER2-ADCpayload altered HER2 gene expression in TDM1R and TDXdR HER2+ BC cell lines.

HER2-directed ADC-resistant HER2+ BC cell lines showed reduced ERBB2 gene amplification. A Fluorescence in situ hybridization analysis. The red color indicates the amplification of ERBB2 gene, and the green color indicates the centromere on chromosome 17 (CEP17). A total of 25 individual cells were evaluated for ERBB2 gene amplification by measuring the HER2/CEP17 ratio from each cell line. Each box shows mean ± s.d.; ****,  P  < 0.0001. Three biological replicated experiments showed similar results. B Whole-genome sequencing data analysis. ERBB2, MIEN1, MIR4728, and PGAP3 gene copy numbers were reduced on chromosome 17 in TDM1R and TDXdR cell lines. C Transcriptome analysis of ERBB2 gene. All ERBB2 probes were pulled out from Affymetrix Clariom D Human microarray data and clustered by differential expression. Expression indicates log2. Data were collected from three biological replicates. D Alternative splicing was increased in ERBB2, MIEN1, MIR4728, and PGAP3 genes on chromosome 17 compared to in parent cells. Transcriptome Analysis Console (TAC, Affymetrix, Inc) software used for the Affymetrix Clariom D Human microarray database to compare differential gene splicing between HER2-ADC-resistant cells and their parent cells. Data were collected from three biological replicates

Alternative splicing is also a well-known mechanism for regulating gene expression [ 35 ]. To measure the alternative splicing of HER2 mRNA in TDM1R and TDXdR BC cell lines, we first checked the binding intensity of all HER2 gene probes using the Clariom D human microarray chip. Gene expression data indicated that 93% (54 of 58) of HER2 gene probes showed reduced HER2 gene expression in both TDM1R and TDXdR BC cell lines compared to in parent cell lines (Fig.  3 C), and we confirmed that the alternative splicing index of ERBB2 , MIEN1 , MIR4728 , and PGAP3 genes was significantly increased in both types of TDM1R and TDXdR BC cell lines, resulting in mRNA reduction (Fig.  3 D). Taken together, our data indicated that ADC-mediated genetic alterations such as deletion, reduction of gene copy number, and alternative splicing cause downregulation of HER2 gene expression in HER2+ BC cell lines.

There are four major potential mechanisms of resistance against ADC: 1) reduced ADC uptake due to the reduction of the target molecule, 2) efflux of the payload, 3) epigenetic modification, and 4) bypass of the payload’s antitumor effect by activation of signaling pathways [ 36 , 37 ]. The mechanism of target protein reduction appears to be at play in our observation of reduced HER2 expression in TDM1R and TDXdR cell lines. To confirm whether reduced HER2 protein level is the reason for T-DXd resistance, we overexpressed HER2 in TDXdR BC cell lines and measured the antiproliferation effect of T-DXd. Overexpression of HER2 did not induce the antiproliferation effect of T-DXd (Fig. S3A). To show that reduced HER2 expression in TDM1R and TDXdR cell lines is sufficient for ADC uptake and therapeutic efficacy, we evaluated the antitumor effect of T-DXd in SUM190-TDM1R and HCC1954-TDM1R xenograft models, which have reduced HER2 expression (Fig.  2 D and Fig. S8C). T-DXd significantly reduced tumor growth in both SUM190-TDM1R and HCC1954-TDM1R xenograft models (Fig.  2 D, P < 0.01). These data indicated that reduced HER2 expression is not a major cause of resistance to HER2-ADC, and reduced HER2 expression in TDM1R and TDXdR BC cell lines is still sufficient to induce tumor growth inhibition by HER2-directed ADC endocytosis.

We did not observe a change in multidrug-resistant genes such as MDR1 and ABCG2 on the microarray analysis, but the epigenetic modulator EGR1 and carrier protein gene SLC6A14 were significantly elevated in TDM1R and TDXdR BC cell lines. To validate whether EGR1 or SLC6A14 is involved in HER2-directed ADC resistance, we knocked them down using RNAi in DXd-resistant BC cell lines and performed a proliferation assay with T-DXd. Silencing of EGR1 or SLC6A14 did not increase the efficacy of T-DXd in SUM190-TDXdR and HCC1954-TDXdR cell lines (Fig. S3B). These data indicated that HER2-directed ADC resistance is not caused by a reduction in intracellular DXd payload level or HER2 expression.

DNA damage response pathway can be targeted to enhance the antitumor effect of T-DXd in TDM1R and TDXdR HER2+ BC cell lines

We confirmed the presence of ERBB2 gene alterations in patients with HER2+ BC after anti-HER2 therapy and in TDM1R and TDXdR HER2+ BC cell lines. Both payloads, DM1 and DXd, are well known to induce DNA damage response pathways due to increased genotoxic stress by inhibition of DNA replication, transcription, recombination, and chromatin remodeling. Hence, we hypothesized that the DNA damage response pathway can be targeted to overcome the resistance to HER2-directed ADCs. We analyzed microarray data from TDM1R and TDXdR BC cell lines using Transcriptome Analysis Console Software to identify canonical pathways and found that DNA damage response was activated in T-DM1R and TDXdR BC cell lines (Fig. S4A). To confirm these findings, we also performed a gene set enrichment analysis and found that a DNA repair, G2M checkpoint, and mitotic spindle pathways were activated in the TDXdR cell lines (Fig.  4 A and Sup. Table 8), which are known to regulate mitosis. In TDM1R BC cell lines, we only observed an activated DNA damage response pathway in SUM190-TDM1R cell line (Sup. Table 9). A further signaling network analysis showed that DNA repair pathway genes—such as non-homologous end joining, mismatch repair, nucleotide excision repair, base excision repair, and homologous recombination repair pathway–related genes—were expressed in TDM1R and TDXdR BC cell lines (Fig. S4B-E). We further determined the expression level of DNA repair pathway proteins using a reverse-phase protein array database and observed up-regulation of ATR, pATR, ATM, Chk1, Chk2, Rad50, and Rad51 in HER2-ADC-resistant cell lines compared to its parent cells (Fig. S4F-H). These data support our hypothesis that DNA damage response pathway inhibition could enhance the efficacy of HER2-directed ADC in HER2-directed ADC–resistant HER2+ BC.

A gene expression analysis and synthetic lethal kinome library high-throughput RNAi screening revealed that the DNA repair pathway is a target for enhancing the efficacy of T-DXd in TDM1R and TDXdR cell lines. A Functional gene-set enrichment analysis using Affymetrix Clariom D Human Transcriptome array data. B Illustration of synthetic lethal kinome library high-throughput RNAi screening. C and D STRING interaction analysis of the top 50 target genes from kinome library high-throughput RNAi screening. K-means clustering was applied to identify groups of genes with similar behavior. Each color indicated co-regulated gene modules related to a specific canonical signaling pathway. SUM190-TDM1R (C), SUM190-TDXdR (D). E Bliss independence dose–response assay. Cells were treated with T-DXd and elimusertib for 5 days, and viability was measured using SRB staining. The data shown are representative of three independent experiments with similar results—the table indicates viability, and the Bliss synergy score was evaluated and visualized using Synergyfinderplus software (right, www.synergyfinderplus.org ). F Clonogenic assay. Cells were treated with T-DXd and/or elimusertib for 14 days, and cell viability was measured by SRB staining. Data are presented as mean ± standard deviation. Two-tailed unpaired Student’s  t -test. Experiments were repeated in triplicate . G . Western blotting. Cells were treated with T-DXd (1 µg/ml) and/or elimusertib (100 nM) for 48 h, and whole-cell lysates were collected for immunoblotting. Protein expression was normalized with actin level in control cells from each TDM1R and TDXdR cell line using ImageJ software. The data shown are representative of three independent experiments with similar results

We identified potential kinase targets whose inhibition could overcome HER2-directed ADC resistance or enhance the antitumor efficacy of HER2-directed ADC in TDM1R and TDXdR BC cell lines. We focused on T-DXd for the synthetic lethal screening because recent clinical trial data indicated that T-DXd is associated with improved overall survival and progression-free survival compared to T-DM1 in patients with HER2+ metastatic BC [ 38 ]; T-DXd is also now a standard second-line therapy in these patients. We performed a non-biased high-throughput RNAi screening in SUM190-TDM1R and SUM190-TDXdR cells using kinome library pooled siRNA, consisting of 2,127 siRNAs targeting 709 kinase genes (Fig.  4 B). Using the Sensitivity Score analysis (described in supplemental information), we selected top 50 target kinases from each of the SUM190-TDM1R and SUM190-TDXdR cell lines (Sup. Table 10). A STRING interactome pathway analysis identified DNA repair pathway–related genes as potential targets for combination therapy with T-DXd in both TDM1R and TDXdR BC cell lines. Ataxia-telangiesctasia, mutated (ATM), ataxia telangiectasia and Rad3-related (ATR), and CDK7 were identified in the SUM190-TDM1R cell line (Fig.  4 C), and ATR was identified in SUM190-TDXdR cell line (Fig.  4 D). Specifically, ATR was overlapped in both cell lines. Taken together, the patient data analysis and synthetic lethal screening data indicated that the DNA repair pathway is a potential target whose inhibition could enhance the efficacy of T-DXd in TDM1R and TDXdR BC cell lines. To verify the RNAi screening result, we tested two additional RNAi targeting ATR and evaluated its synergistic antiproliferation effect with T-DXd in HER2 ADC-resistant HER2+ BC cell lines. We observed that two ATR RNAi significantly inhibited growth and showed a combination antiproliferation effect with T-DXd in tested all HER2+ BC cell lines ( P  < 0.05, Fig. S5A and S5B).

ATR inhibitor elimusertib enhanced the antitumor efficacy of T-DXd in TDM1R and TDXdR HER2+ BC xenograft models

Patients’ gene alteration and gene expression data (Fig.  1 ), microarray data in TDM1R and TDXdR cell lines (Fig.  4 A and Fig. S4A), and kinome RNAi screening results (Fig.  4 C and D) indicated that the PI3K, cell cycle and DNA repair pathways are potential targets for combination therapy with T-DXd in TDM1R and TDXdR HER2+ BC. To validate which target can enhance the efficacy of T-DXd in TDM1R and TDXdR cell lines, we selected specific kinase inhibitors against PI3K (alpelisib), CDK4/6 (abemaciclib), Wee1 (AZD1775), Aurora kinase A (TAS-119), ATR (elimusertib), and PARP inhibitor (olaparib) for proliferation assays. We limited drugs that were only FDA-approved or had been used for clinical trials. As single agents, abemaciclib and elimusertib showed significant growth inhibition in all tested TDM1R and TDXdR cell lines (> 60% GI), but alpelisib, AZD1775, TAS-119, and olaparib did not (Fig. S5C and S5D). In combination with T-DXd, we found that only the ATR inhibitor elimusertib showed an enhanced antiproliferation effect in both T-DM1R and TDXdR BC cell lines (Fig. S5C and S5D). To evaluate the combination effect of T-DXd and elimusertib, we conducted a Bliss independence dose–response surface model [ 39 , 40 ] under the 5-day short-term treatment condition. Compared to T-DXd or elimusertib monotherapy, combination therapy significantly inhibited antiproliferation in all tested TDM1R and TDXdR cell lines (Bliss synergy score: 11.34 in SUM190; 10.54 in SUM190-TDM1R; 10.14 in SUM190-TDXdR; 17.88 in HCC1954; 5.04 in HCC1954-TDM1R; 6.68 in HCC1954-TDXdR) (Fig.  4 E, Sup. Figure 5E and 5F). Additionally, we tested small molecules Gartisertib (ATR inhibitor) and AZD1390 (ATM inhibitor) to confirm the target specificity of the DNA repair pathway. Similar to elimusertib and T-DXd combination data, we observed an enhanced antiproliferation effect in combination treatment in HER2 ADC-resistant SUM190 and HCC1954 cell lines (Fig. S5G and S5H). These data indicated that the DNA repair pathway, particularly ATR, is a potential target for combination with T-DXd in TDM1R and TDXdR HER2+ BC.

Next, we examined the combination effect of T-DXd and elimusertib on long-term treatment conditions using a clonogenic assay. Compared to T-DXd or elimusertib monotherapy, combination therapy significantly inhibited antiproliferation in all tested TDM1R and TDXdR cell lines ( P  < 0.0001 in SUM190-TDM1R; P  < 0.01 in SUM190-TDXdR; P  < 0.001 in HCC1954-TDM1R; P  < 0.01 in HCC1954-TDXdR) (Fig.  4 F).

We next determined whether the enhanced antiproliferation effect of the combination treatment was a result of apoptosis induction by ATR inhibition. In the SUM190-TDM1R and SUM190-DXdR cell lines, the combination of T-DXd and elimusertib induced DNA damage marker pH2AX and cleaved PARP expression compared to single-agent treatment with T-DXd or elimusertib (Fig.  4 G, left panel, and Fig. S6A). In HCC1954-TDM1R cells, elimusertib single-agent treatment significantly induced pH2AX. The combination of T-DXd and elimusertib did not induce an increase in the apoptosis marker cleaved PARP but did result in reduced full-length PARP expression compared to single-agent T-DXd and elimusertib. We speculate that the apoptosis pathway activated before the 48-h time point. In HCC1954-TDXdR cells, we observed enhanced cleaved PARP expression upon combination treatment, but pH2AX expression was not increased by the combination treatment compared to single-agent elimusertib (Fig.  4 G, right panel, and Fig. S6A). Unlike the reduction of HER2 expression by T-DXd treatment, pHER2 expression was significantly increased by T-DXd in all tested cell lines (Fig.  4 G).

We determined whether elevated pHER expression affects its downstream molecules. We first analyzed a reverse-phase protein array database and observed downregulation of HER2 and upregulation of pHER2 expression with T-DXd treatment; however, we did not observe significantly increased expression of key downstream molecules, such as pAKT, pmTOR, pS6K, p70S6K, pMEK1, and pMAPK (pERK) (Fig. S6B). Further, we validated the reverse-phase protein array data using Western blotting and confirmed that T-DXd-mediated pHER2 induction does not induce its downstream molecules, pAKT and pERK (Fig. S6C and S6D).

Our in vitro data demonstrated that ATR inhibition enhances the efficacy of T-DXd in HER2-directed, ADC-resistant HER2+ BC cells. Next, we examined the synergistic antitumor effect of T-DXd and elimusertib in SUM190-TDM1R, SUM190-TDXdR, HCC1954-TDM1R, and HCC1954-TDXdR xenograft models. The doses were 10 mg/kg for T-DXd [ 7 ] and 10 mg/kg for elimusertib [ 41 ]. Compared to vehicle control, single-agent T-DXd treatment showed significant tumor shrinkage in both SUM190-TDM1R (74% shrinkage, P  < 0.0001) and HCC1954-TDM1R (75% shrinkage, P  < 0.0001) xenograft models until days 35–40, when recurrence occurred (Fig.  5 A and B). Elimusertib single-agent treatment did not have an antitumor effect but showed a synergistic antitumor effect with T-DXd, and this combination showed more sustained tumor shrinkage than did T-DXd single-agent treatment in both the SUM190-TDM1R ( P  < 0.0086) and HCC1954-TDM1R ( P  < 0.0383) models (Fig.  5 A and B). After the completion of combination treatment, some mice showed no residual tumors (3 of 13 mice with SUM190-TDM1R and 4 of 12 mice with HCC1954-TDM1R). In the SUM190-TDXdR xenograft model, single-agent T-DXd treatment did not show tumor shrinkage but rather continual tumor growth. As in the T-DM1-resistant model, single-agent elimusertib treatment did not show tumor growth inhibition (TGI); however, elimusertib combined with T-DXd showed a significant TGI effect compared to single-agent T-DXd in the SUM190-TDXdR model (Fig.  5 C, 57% TGI, P  < 0.0305). In the HCC1954-TDXdR xenograft model, we did not observe significant TGI upon combination treatment with T-DXd and elimusertib compared to single-agent T-DXd (Fig.  5 D, 33% TGI, P  < 0.5795). However, when we performed a paired comparison analysis, only three mice bearing HCC1954-TDXdR xenografts treated with the combination showed tumor progression; the remaining five mice showed tumor shrinkage or growth inhibition in the combination treatment group.

Combination treatment with T-DXd and elimusertib enhanced the antitumor effect compared with monotherapy in TDM1R and TDXdR HER2+ BC in vitro and in vivo. A-D Xenograft assay using SUM190-TDM1R ( A ), HCC1954-TDM1R ( B ), SUM190-TDXdR ( C ), and HCC1954-TDXdR ( D ). Cells were injected into the mammary fat pad of nude mice, and treatments were started when tumors were an average of 200—250 mm 3 . T-DXd (10 mg/kg) was administered one time on Day 0 via tail-vein injection. Elimusertib (10 mg/kg) was administered via oral gavage twice a day (6-h intervals) for 3 consecutive days per week. Data are presented as mean ± standard deviation. Left , tumor growth and tumor weight (endpoint) measurements. Table shows multiple t -tests between T-DXd and combination on each measurement date. Right , IHC images of expression levels of HER2, pH2AX, pATR, and Ki-67 in xenograft tumor tissues. Multiple t -test comparison tests were used for tumor growth. Table shows t -tests between T-DXd and a combination of elimusertib and T-DXd on each measurement date. A two-tailed unpaired Student’s  t -test was used for tumor weight comparison. Scale bars = 200 µm. IHC intensity was evaluated using the ImageJ program. Each box shows the mean with standard deviation. *  P  < 0.05, **  P  < 0.01, ***  P  < 0.001, ****  P  < 0.0001. The data shown are representative of three tumor samples per group with similar results

We analyzed the expression levels of HER2, Ki-67, pATR, and pH2AX in xenograft tissues by IHC staining as observed in the Western blotting data (Fig.  4 G), the expression levels of HER2, pATR, and Ki-67 were reduced in tumors from SUM190-TDM1R and HCC1954-TDM1R xenograft models treated with T-DXd combined with elimusertib compared to single-agent treatment with T-DXd or elimusertib (Fig.  5 A and B). In tumors from SUM190-TDXdR and HCC1954-TDXdR models, we observed only the inhibition of proliferation marker Ki-67 by T-DXd combined with elimusertib (Fig.  5 C and D). We speculate that a one-time injection of T-DXd is not sufficient to enhance tumor cell death on long-term follow-up because both SUM190-TDXdR and HCC1954-TDXdR xenograft models showed recurrence in all groups. There was no body weight loss in the mice treated with T-DXd, elimusertib, or the combination during the treatment period (Fig. S7), supporting the safety of the tested T-DXd and elimusertib treatment dose and schedule. Taken together, these results suggest that the ATR inhibitor elimusertib enhances the antitumor effect of T-DXd via the DNA damage pathway in both T-DM1- and T-DXd-resistant HER2+ BC. The IHC results demonstrated strong HER2 expression in all TDM1R and TDXdR BC xenograft models. The drug treatment started between 14 to 21 days after cell inoculation into mice. To confirm whether HER2 expression was restored during tumor engraftment in mice, we stopped T-DM1 and T-DXd treatment in all cell lines for 1 month and measured total and cell surface HER2 expression levels by Western blotting and FACS analysis, respectively (Fig. S8A and S8B), as well as IHC staining in SUM190 and HCC1954 parent tissue samples (Fig. S8C). We confirmed that HER2 levels were continually downregulated in TDM1R and TDXdR BC in cell lines and xenografts. These data indicated that the enhanced HER2 signals were caused by detection conditions without parent tissue samples.

In the management of HER2+ BC, FDA-approved therapies such as T-DM1 and T-DXd have markedly improved survival rates. However, resistance to HER2-directed ADCs remains a challenge, with no established therapy post-resistance to T-DXd. Our translational research underscores the importance of the DNA repair pathway in this resistance, identifying it as a potential therapeutic target. We discovered that chronic exposure to T-DM1 or T-DXd reduces HER2 expression and induces oncogenic transformation such as copy number variation, gene amplifications, and epigenetic modifications. Further, enhanced DNA repair activity post-ADC treatment in patient samples suggests new intervention opportunities. Additionally, using a synthetic lethal kinome library RNAi screen informed by patient data, in non-biased manner, we identified targets that significantly increase T-DXd's effectiveness. Our preclinical models show that combining T-DXd with elimusertib, an ATR inhibitor, is a promising strategy to overcome resistance. These results support integrating DNA repair inhibitors into the therapeutic repertoire for HER2 ADC-resistant BC tumors, thus representing a significant advance in treatment protocols.

Although tremendous progress has been achieved with targeted therapy for HER2+ BC, these tumors eventually develop resistance. A better understanding of the mechanisms of resistance to anti-HER2 therapy is needed to develop new therapeutic approaches. While several mechanisms of resistance to trastuzumab or T-DM1 have been described, there is no comprehensive analysis identifying the mechanisms of resistance to T-DXd in HER2+ BC, but it is expected that some mechanisms described for trastuzumab and/or T-DM1 can be extrapolated to T-DXd. Alterations in the ERBB2 gene are considered a representative mechanism of resistance to anti-HER2 therapies. In fact, our current study showed frequent HER2 loss in models of resistance to trastuzumab and pertuzumab or T-DM1. Since T-DM1 and T-DXd are ADCs directed against HER2, HER2 loss or decreased HER2 expression is a possible cause of resistance [ 42 , 43 ]. A recent study affirmed HER2 status changes in metastatic HER2+ BC after treatment, and patients with loss of HER2 showed worse responses to T-DM1 and inferior overall survival [ 44 ]. In the KRISTINE trial, a phase III trial of neoadjuvant T-DM1 and pertuzumab in HER2+ BC, a subgroup of 15 patients treated with T-DM1 and pertuzumab who had locoregional progression before surgery showed high heterogeneity in HER2 expression, which may have contributed to the worse clinical outcomes observed with T-DM1 treatment [ 45 ]. In vitro, several cell lines generated with acquired resistance to T-DM1 showed a decrease in HER2 expression compared to parent cells [ 46 , 47 , 48 , 49 , 50 ].

Recently, HER2-directed ADC has been used for targeted systemic delivery of chemotherapeutic agents as payload, such as DM1, DXd, duocarmycin, monomethyl auristatin F, and monomethyl auristatin E, to inhibit DNA replication. Due to the mechanism of action of the payload, chemotherapeutic agents cause DNA alterations, including mismatches, single-strand breaks, and double-strand breaks, resulting in gene mutation and genome instability [ 51 ]. Thus, cancer cells activate the DNA damage response to escape chemotherapeutic agent–mediated cell death. To overcome the drug resistance related to the DNA repair pathway, inhibitors of ATM, ATR, CHK1, Wee1, DNA-PK, and PARP are potential candidates for enhancing these chemotherapies and are currently in clinical trials in combination with other anticancer drugs. ATM mutations have been associated with an increased risk of BC [ 52 , 53 ]. A preclinical study indicated that Wee1 inhibitor use has potential clinical applications in overcoming trastuzumab resistance in BC [ 54 ]. Also, the PARP inhibitor olaparib showed a synergistic antitumor effect with T-DXd in HER2+ and HER2-low BC xenograft models [ 55 ].

In the phase 2 DAISY trial (ClinicalTrials.gov identifier: NCT04704661) [ 56 ], the authors found that SLX4 loss of function mutation is absorbed in T-DXd-resistant HER2+ BC patients and has a role in the T-DXd resistance mechanism in BC cell lines. In our study, we investigated HER2 and other gene alterations in patient samples and cell lines after the development of HER2-directed ADC resistance and found alterations of genes related to the DNA repair pathway. We did not observe SLX4 mutation in five matched pre- and post-T-DXd treatment tissue samples or five post-T-DXd treatment samples. Indeed, WGS data from SUM190 parent, SUM190-TDM1R, and SUM190-TDXdR cell lines showed SLX4 mutation, but HCC1954 cell lines showed no changes in SLX4 mutation (Fig. S9). Unlike in other studies, SUM190 cells were more sensitive to T-DXd treatment than were other HER2+ cell lines. These data implied that SLX4 is not a single driver in resistance to T-DXd. Thus, further investigations are needed to elucidate the function of SLX4 mutation.

Increasing studies have found that drug resistance in cancer cells is closely tied to the DNA repair regulatory system. In HER2+ cancers, there is an ongoing phase I/IB clinical trial of the combination of T-DXd and an ATR inhibitor in patients with advanced solid tumors expressing the HER2 protein or gene (DASH trial, ClinicalTrials.gov identifier: NCT04704661). ADCs are designed to elicit a tumor-selective therapeutic effect; however, some adverse effects are considered a clinical obstacle to developing combination regimens with DNA repair pathway–targeting inhibitors. The most common adverse effects of HER2-directed ADC are fever, nausea, vomiting, and hematologic toxicity [ 57 , 58 ]. In the DESTINY-Breast01 trial, T-DXd was associated with leukopenia, anemia, fatigue, nausea, interstitial lung disease, and neutropenia [ 9 ]. The ATR inhibitor elimusertib has antitumor activity in advanced solid tumors, including BC [ 41 , 59 ]. The most common treatment-emergent adverse events were generally hematologic and comprised anemia (81.8%, grade 3), neutropenia (72.7%, grade 3/4), and thrombocytopenia (45.5%, grade 3/4). Fatigue (68.2%, grade 2) and nausea (50.0%, grade 3) were also reported (ClinicalTrials.gov identifier: NCT03188965) [ 59 ]. Therefore, more severe hematologic adverse events are expected to occur when patients are treated with T-DXd and elimusertib together. To reduce severe hematological adverse events, dose de-escalation or sequential treatment with T-DXd and elimusertib, rather than concomitant treatment, should be considered. The most common concentration of elimusertib used in preclinical xenograft models is 20–50 mg/kg [ 41 , 60 ]. In our preclinical studies, 10 mg/kg of single-agent elimusertib did not show an antitumor effect, but it enhanced the antitumor effect of T-DXd in TDM1R and TDXdR xenograft models. These data suggest that dose de-escalation of a DNA repair–targeting drug should be considered for the clinical dosing schedule.

Another interesting finding was the significant enrichment of immune-related gene sets in pre-T-DXd samples, including Interferon_Alpha_Response, Interferon_Gamma_Response, and IL6_Jak_Stat3_Signaling (Sup. Table 7). These data indicated an active immune response within the tumor microenvironment in the pre-TDXd treatment group, which turned into an inactive tumor microenvironment after treatment. In the phase 2 DAISY trial, the investigators found that CD68-positive tumor cell-proximate macrophages were significantly decreased after T-DXd treatment [ 56 ]. A phase 1b study explored the potential immune system activation benefits of combining atezolizumab and anti-HER2 therapies, including T-DM1, and observed increased PD-L1 levels and CD8 + T-cell infiltration in HER2+ BC [ 61 ]. High infiltration of M1-like macrophages and CD8 + T-cells in tumors is associated with better response to trastuzumab therapy in HER2+ BC [ 62 ]. Another study observed that high tumor-infiltrated lymphocytes were associated with trastuzumab efficiency and improved survival in BC [ 63 ]. Although clinical and preclinical data indicated that the T-DXd and immune checkpoint inhibitor combination [ 64 ] is feasible, further investigation is required to elucidate the mechanism of the action of T-DM1 andT-DXd in BC because BC is a heterogenous tumor immune microenvironment due to genetic instability, epigenetic modification, immune cell spatial heterogeneity, and tumor-associated stromal cells such as cancer-associated fibroblasts and adipocytes.

While our study offers valuable insights into the mechanisms of resistance to HER2-directed ADCs and the potential of targeting the DNA repair pathway, it is important to consider certain limitations. Our research primarily uses preclinical models, which may not fully capture the diverse genetic backgrounds found in the HER2+ breast cancer patient population. The variability in cancer resistance mechanisms suggests that further investigation is needed to confirm the efficacy of targeting the DNA repair pathway alongside T-DXd across different cancer types and resistance mechanism. Although we have identified the DNA repair pathway as a promising target, more detailed studies are required to fully understand the mechanisms of resistance and how pathway inhibition enhances T-DXd efficacy. Additionally, expanding the number of patient samples in future studies will be crucial for identifying robust biomarkers, thereby strengthening our approach and enhancing the clinical applicability of our findings.

In summary, our study identified the induction of HER2 gene alteration and activation of the DNA repair pathway in HER-ADC-resistant BC cell lines and HER2+ BC patients. We validated that the inhibition of the DNA repair pathway can increase sensitivity to T-DXd treatment in TDM-1 resistant and T-DXd resistant BC in vitro and in vivo . This preclinical study provides justification for conducting clinical trials with HER2+ BC patients who develop resistance to T-DM1 or T-DXd treatment. We will need for identification of predictive biomarkers that will aid the selection of patients for treatment with T-DXd and the DNA repair pathway–targeted agents.

Availability of data and materials

The datasets generated and/or analyzed during the current study, including whole genome sequencing and microarray data, are available from the corresponding author upon request.

Abbreviations

Breast cancer

Human epidermal growth factor receptor 2 positive

Trastuzumab emtansine

Trastuzumab deruxtecan

Antibody–drug conjugate

T-DM1–resistant

T-DXd–resistant

RNA interference

Immunohistochemistry

Tumor growth inhibition

Institutional Review Board

Gene Set Enrichment Analysis

False Discovery Rate

Normalized Enrichment Score

Copy number variation

Formalin-Fixed Paraffin-Embedded

Fluorescence-activated Cell Sorting

Ataxia Telangiectasia Mutated

Ataxia Telangiectasia and Rad3-Related

Poly (ADP-Ribose) Polymerase

Search Tool for the Retrieval of Interacting Genes/Proteins

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Acknowledgements

We thank Sarah Bronson and Ann Sutton of the Research Medical Library at The University of Texas MD Anderson Cancer Center for their expert editorial assistance. We acknowledge Drs. Daohong Zhou and Daifeng Jiang for their assistance with the high-throughput kinome library RNAi screening, which was performed at the Target Identification Facility of the Greehey Children’s Cancer Research Institute at The University of Texas Health San Antonio and the Drug Discovery and Structural Biology Shared Resources of the Mays Cancer Center at The University of Texas Health San Antonio. We also thank Kyung Hun Lee at the Department of Internal Medicine, Seoul National University Hospital, for providing crucial feedback, and we thank the Center for Precision Medicine, Seoul National University Hospital, for their contribution to the targeted DNA sequencing. The facilities were partially supported by P30CA054174 from NIH and RP160844 from CPRIT. BioRender was used to create illustrations.

This work was supported by University of Hawaii Cancer Center Support Grant (P30CA071789; Shared Resources), MD Anderson’s Cancer Center Support Grant (P30CA016672; Cytogenetics and Cell Authentication Core, Advanced Technology Genomics Core, RPPA-Functional Proteomics Core, DVMS Veterinary Pathology Services, Flow Cytometry and Cellular Imaging Core, and Research Animal Support Facility), the Morgan Welch Inflammatory Breast Cancer Research Program, the State of Texas Rare and Aggressive Breast Cancer Research Program, and Daiichi Sankyo Company, Limited. Sequencing and analysis at Seoul National University Hospital were partly funded by the Ministry of Health and Welfare, Republic of Korea [grant number: HR14C0003].

Author information

Kumiko Kida

Present address: Present address: Department of Breast Surgical Oncology, St. Luke’s International Hospital, 9-1, Akashicho, Chuouku, Tokyo, 104-8560, Japan

Jangsoon Lee and Kumiko Kida contributed equally to this work.

Authors and Affiliations

Section of Translational Breast Cancer Research and Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Jangsoon Lee, Kumiko Kida, Huey Liu, Young Jin Gi, Debu Tripathy & Naoto T. Ueno

Cancer Research Institute, Seoul National University, Seoul, Republic of Korea

Jiwon Koh, Dae-Won Lee & Seock-Ah Im

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Ganiraju C. Manyam

Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Asha S. Multani & Jing Wang

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Gitanjali Jayachandran & James M. Reuben

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Aysegul Sahin & Lei Huo

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro Jongro-Gu, Seoul, 03080, Republic of Korea

Dae-Won Lee & Seock-Ah Im

Cancer Biology and Therapeutics, University of Hawai‘I Cancer Center, 701 Ilalo Street, Room 622, Honolulu, HI, 96813, USA

Jangsoon Lee, Young Jin Gi, Dileep R. Rampa & Naoto T. Ueno

Present address: Cancer Biology Program, University of Hawai’I Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA

Jangsoon Lee

You can also search for this author in PubMed   Google Scholar

Contributions

Conceptualization: J. Lee, K. Kida, S-A. Im, N. Ueno. Data curation: J. Lee, J. Koh, D. Reddy, G. Manyam, A. Multani, G. Jayachandran, N. Ueno. Formal Analysis: J. Lee, K. Kida, J. Koh, D. Reddy, G. Manyam, A. Multani, H. Liu, G. Jayachandran, Y. Gi. Methodology: J. Lee, J. Koh, G. Manyam, A. Multani, G. Jayachandran. Writing – original draft: J. Lee, K. Kida, J. Koh, S-A. Im, N. Ueno. Writing – review & editing: J. Lee, K. Kida, A. Multani, G. Manyam, J. Wang, J. Reuben, L. Hui, D. Tripathy, A. Sahin, S-A. Im, N. Ueno. Administrative and resources: J. Lee, Wang, J. Hui, D, Reuben, L, D. Tripathy, A. Sahin, DW Lee. S-A. Im, N. Ueno. Study supervision: J. Lee, K. Kida, S-A. Im, N. Ueno.

Corresponding authors

Correspondence to Jangsoon Lee , Seock-Ah Im or Naoto T. Ueno .

Ethics declarations

Ethics approval and consent to participate.

Xenograft studies were approved by the Institutional Animal Care and Use Committee of MD Anderson (00001032-RN03). This study was approved by the MD Anderson IRB (PA15-0499) or Seoul National University Hospital IRB (2310–165-1480) and conducted in agreement with the requirements of the Code of Federal Regulations and the IRB.

Consent for publication

All patients signed an IRB-approved consent form indicating their agreement to participate. The consent form includes the nature, objectives, and potential risks and benefits of the study and details the required length of follow-up, required tissue biopsies and blood sample collections, and the name of the principal investigator responsible for the protocol. The consent also specifies the patient’s right to accept or refuse treatment, terminate participation, and withdraw from the protocol. All data were collected in accordance with the human subjects research policies of MD Anderson and Seoul National University Hospital.

Competing interests

Naoto T. Ueno and Jangsoon Lee have contracted research with Daiichi Sankyo. Seock-Ah Im reports advisory role for AstraZeneca, Daiichi-Sankyo, Eisai, Hanmi, Idience, Lilly, MSD, Novartis, Pfizer, Bertis, and Roche and has received research grants through her institution from AstraZeneca, Boryung Pharm, Daiichi-Sankyo, Daewoong Pharm, Eisai, Pfizer, and Roche. All other authors declare no competing interests.

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Supplementary Information

Supplementary material 1:.

Supplementary Tables.

Supplementary Material 2: Supplementary Figure S1.

Antiproliferation effect of T-DM1 and T-DXd in HER2-positive BC cell lines. A. HER2 gene copy variation in HER2+ BC cell lines. The TNBC cell line MDA-MB-231 was used as a negative control. Genomic DNA was used for the ddPCR assay. Each box shows mean with standard deviation. Data were collected from three biological replicates. B. T-DM1 and T-DXd inhibited the proliferation of HER2+ cell lines in a dose-dependent manner. Cells were treated with T-DM1 or T-DXd for 5 days, and viability was measured using SRB staining. The data shown are representative of 3 independent experiments with similar results. C. T-DM1 and T-DXd significantly reduced tumor volume in HER2+ BC cell xenograft models. SUM190 or HCC1954 cells were injected into the mammary fat pad of nude mice, and the treatment was started when tumors averaged 200 mm 3 . HER2-ADC (10 mg/kg) was administered one time on Day 0, and tumor size was monitored. An IHC assay was used to check the expression levels of HER2 and proliferation maker Ki-67 in tumor samples. The data shown represent three IHC staining experiments from each treatment group with similar results. 20× magnification. Scale bars, 200 μm. In vivo tumorigenicity data were compared using an analysis of the variance model. **  P < 0.01, ***  P < 0.001.    Supplementary Figure S2. A. HER2-ADC cell lines did not show an increase in genomic instability. Thirty-five metaphases/anaphases were analyzed per cell line. B. Deletion of the amplified ERBB2 region was observed on chromosome 17 in the SUM190-TDXdR cell line. Karyotyping assay. C. The intrinsic T-DXd-resistant KPL4 cell line (KPL4-TDXdR) did not show reduced ERBB2, MIEN1, MIR4728, and PGAP3 gene copy numbers. Whole-genome sequencing analysis.  Supplementary Figure S3. A. Overexpression of HER2 did not increase the antiproliferation effect of T-DXd in T-DXd resistant HER2+ BC cell lines. SUM190-TDXdR and HCC1954-TDXdR cells transfected with pcDNA3-HER2 plasmid (Addgene, Watertown, MA, USA) using the Neon transfection kit (ThermoFisher) and underwent an SRB proliferation assay with T-DXd. The remaining cells were used for immunoblotting to check overexpression of HER2. B. Cells were transfected with validated siRNA targeting EGR1 or SLC6A14 (Silencer select Hm genome siRNA library v4, ThermoFisher) using the Neon transfection kit and incubated for 48 hr; they then underwent an SRB proliferation assay with T-DXd. Supplementary Figure S2. A. HER2-ADC cell lines did not show an increase in genomic instability. Thirty-five metaphases/anaphases were analyzed per cell line. B. Deletion of the amplified ERBB2 region was observed on chromosome 17 in the SUM190-TDXdR cell line. Karyotyping assay. C. The intrinsic T-DXd-resistant KPL4 cell line (KPL4-TDXdR) did not show reduced ERBB2, MIEN1, MIR4728, and PGAP3 gene copy numbers. Whole-genome sequencing analysis. Supplementary Figure S3. A. Overexpression of HER2 did not increase the antiproliferation effect of T-DXd in T-DXd resistant HER2+ BC cell lines. SUM190-TDXdR and HCC1954-TDXdR cells transfected with pcDNA3-HER2 plasmid (Addgene, Watertown, MA, USA) using the Neon transfection kit (ThermoFisher) and underwent an SRB proliferation assay with T-DXd. The remaining cells were used for immunoblotting to check overexpression of HER2. B. Cells were transfected with validated siRNA targeting EGR1 or SLC6A14 (Silencer select Hm genome siRNA library v4, ThermoFisher) using the Neon transfection kit and incubated for 48 hr; they then underwent an SRB proliferation assay with T-DXd.  Supplementary Figure S4. A. An Affymetrix Clariom D Human Transcriptome array data analysis identified targetable canonical pathways. TAC software was used to analyze and visualize global expression patterns of genes and pathways. The cut-off range was two-fold expression change (up and down) and P < 0.001. Significance was calculated using a 2x2 contingency in a Fisher’s exact test (two-sided). After the P value was established using Fisher’s exact test, it was converted to -log10. B-E. DNA repair pathway network analysis of microarray data from HER2-ADC-resistant cell lines. The cut-off range is the two-fold expression change (up and down) and P < 0.001. Significance was calculated using a 2x2 contingency in a Fisher’s Exact Test (two-sided). SUM190-TDM1R (B), HCC1954-TDM1R (C), SUM190-TDXdR (D), and HCC-1954TDXdR (E). Data were collected from three biological replicates. E-G. DNA repair pathway related proteins were elevated in HER2-ADC-resistant cell lines compared to is of microarray data from HER2-ADC-resistant cell lines. ATR, pATR, Chk1, Chk2, ATM, Rad50, and Rad51 were elevated in HER2-ADC-resistant cell lines. Reverse-phase protein array data (F). Hierarchical Clustering of reverse-phase protein array data using Morpheus software (https://software.broadinstitute.org/morpheus) Median expression values used for analysis (G). STRING interactome analysis of ATR, pATR, Chk1, Chk2, ATM, Rad50, and Rad51 (H).  Supplementary Figure S5. DNA repair pathway–targeting drug enhances the efficacy of T-DXd in HER2-ADC-resistant HER2+ BC cell lines. A. Knockdown of ATR significantly reduces viability of HCC1954-TDXdR cell line. Two ATR RNAi were individually transfected, and SRB proliferation assay conducted for 7 days. B. ATR RNAi significantly enhances the efficacy of T-DXd in HER2+ BC. Cell lysates were collected at 72 hr after transfection for Western blotting analysis. The data shown are representative of three independent experiments with similar results. C and D. Clonogenic assay. Cells were treated with T-DXd and/or selected kinase inhibitor for 14 days, and cell viability was measured by SRB staining. SUM190-TDM1R and SUM190-TDXdR cell lines (C). HCC1954-TDM1R and HCC1954-TDXdR cell lines (D). Data are presented as mean ± standard deviation. Two-tailed unpaired Student’s  t -test; *,  P  < 0.05, **,  P  < 0.01, ***,  P  < 0.001, ****,  P  < 0.0001, n.s. not significant. Experiments were repeated in triplicate. The data shown are representative of three independent experiments with similar results. E - H. Bliss independence dose-response assay. Cells were treated with T-DXd and selected inhibitors for 7 days, and viability was measured using SRB staining. The cell images were captured using GelCounter , the table indicates viability, and the Bliss synergy score was evaluated and visualized using the Synergyfinderplus software (right, www.synergyfinderplus.org). The color indicates a synergist (red) or antagonist (green) effect in two-drug combinations.  Supplementary Figure S6. A. T-DXd and elimusertib increased DNA damage stress and apoptosis. Western blotting assay. Cells were treated with T-DXd (1 µg/ml) and/or elimusertib (100 nM) for 48 h, and whole-cell lysates were collected for immunoblotting. Protein expression was normalized with actin level in control cells from each TDM1R and TDXdR cell line using ImageJ software. B. T-DM1 or T-DXd treatment did not induce the HER2 downstream molecules, pAKT and pMAPK. Reverse-phase protein array data. Cells  C and D. Western blotting. Basal levels of HER, pHER2, pAKT, and pERK in parent and HER2-ADC-resistant cell lines (C). T-DXd treatment does not induces pAKT and pERK expression (D). The ImageJ program was used to measure intensity.  Supplementary Figure S7. T-DXd and elimusertib did not show toxicity in xenograft models. T-DXd (10 mg/kg) was administered one time on Day 0 via tail-vein injection. Elimusertib (10 mg/kg) was administered via oral gavage twice a day (6-hr interval) for 3 consecutively days per week. Data are presented as mean ± standard deviation.  Supplementary Figure S8. Reduced HER2 expression level is retained in HER2-ADC-resistant cell lines without T-DM1 or T-DMd treatment. To match xenograft assay conditions, HER2-ADC-resistant cell lines were maintained without the drug for 2 months. A. Western blotting. TDM1R and TDXdR cell lines retained reduced HER2 expression compared to the parent cell line. The ImageJ program was used for measuring intensity. B. FACS analysis. TDM1R and TDXdR cell lines showed reduced cell-surface HER2 expression. C. The sections (5-μm thick) were used for IHC staining, as described in the Methods section. The slides were then incubated with anti-HER2. Immunostained slides were scanned using an Aperio AT2 slide scanner and captured at 20× magnification using Aperio ImageScope software (Leica Biosystems). Scale bars = 200 µm.  Supplementary Figure S9. Genes mutation profiling of the DNA repair pathway in HER2-ADC-resistant cell lines. Whole-genome sequencing data.

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Lee, J., Kida, K., Koh, J. et al. The DNA repair pathway as a therapeutic target to synergize with trastuzumab deruxtecan in HER2-targeted antibody–drug conjugate–resistant HER2-overexpressing breast cancer. J Exp Clin Cancer Res 43 , 236 (2024). https://doi.org/10.1186/s13046-024-03143-3

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Received : 11 May 2023

Accepted : 30 July 2024

Published : 21 August 2024

DOI : https://doi.org/10.1186/s13046-024-03143-3

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Clinical Trials

Over the past 40 years, breast cancer treatment has greatly improved due to findings from clinical trials.

Clinical trials test the safety and benefits of new treatments as well as new combinations (or new doses) of standard treatments. They can also study other parts of care including risk reduction, diagnosis and screening.

People volunteer to take part in clinical trials. Those who join help further the knowledge base that improves breast cancer care.

Ask your health care provider if there are any clinical trials that are right for you. After discussing the benefits and risks with your provider, we encourage you to consider joining a clinical trial.

The importance of clinical trials

Whether a new therapy or test becomes part of the standard of care for breast cancer depends largely on clinical trial results.

For example, clinical trials showed the benefit of tamoxifen (Nolvadex) and  trastuzumab (Herceptin) and these drugs are now part of the standard of care for breast cancer. 

Findings from large randomized clinical trials are viewed as the best source for making treatment guidelines.

Dedicated physicians, researchers and other health professionals, as well as hospitals, medical research centers and funders are all key to clinical trials. However, most important are the participants.

Learn how Komen is helping people with any stage of breast cancer find and participate in clinical trials, including trials supported by Komen .

Lajos Pusztai, M.D., D. Phil. Komen Scholar

“Clinical trials provide a chance to receive tomorrow’s therapies today.”

Where do clinical trials take place?

Clinical trials take place across the country (and around the world) in many types of medical centers and hospitals.

Cooperative group clinical trials

Cooperative group clinical trials are funded by a single agency like the National Cancer Institute (a government agency) and are done at the same time in many sites across the country. This allows researchers to increase the number of people in a study.

Phases of cancer treatment trials

There are 4 main phases of clinical trials for new breast cancer treatments.

Phase 1 (phase I) trials

A phase 1 trial studies whether a new treatment is safe to use over a range of doses. It’s mainly a drug safety study.

The treatment may be given to people with different types of cancers.

Phase 2 (phase II) trials

A phase 2 trial studies whether a drug (or other therapy) is an effective treatment for a certain cancer, such as breast cancer. These trials typically include 25-100 people.

If a treatment is found to be effective in a phase 2 trial, a phase 3 trial will study it further.

Phase 3 (phase III) trials

A phase 3 trial studies how well a new treatment (including surgical procedures) works compared to standard treatment (standard of care).

It studies the best way to give the new treatment to get the most benefit and whether the new treatment is better than standard treatment.

A phase 3 trial may study different doses of the same drug, different drug combinations or different sequences of giving drugs (for example, which drug is best to give first).

In a phase 3 trial, people are randomized (chosen by chance) to get either the new treatment or standard treatment. They don’t get to choose which treatment they will get. Their health care providers also don’t get to choose which treatment each participant will get. This makes sure the study results reflect the true benefits and risks of the new treatment.

Some studies are double-blinded randomized trials. This means neither the participants in the trial nor the researchers know which treatment each participant is getting (until the clinical trial is over). In addition, a participant’s health care provider will not know which treatment the participant is getting.

Phase 4 (phase IV) trials

A phase 4 trial studies the long-term side effects of a treatment or answers new questions about the treatment. It’s done after a breast cancer treatment is approved by the U.S. Food and Drug Administration (FDA-approved).

Other phases of clinical trials

Not all clinical trials fall neatly into one category. Some trials may be a combination of 2 categories, such as a phase 1/2 or phase 2/3 trial.

Phase 0 (early phase 1) trials

Phase 0 (also called early phase 1) clinical trials are different from other phases of clinical trials because they have no treatment goals and they’re not part of the FDA approval process [ 259 ].

Phase 0 trials can give information on whether a drug does what it’s expected to do (based on cell and/or animal data) [ 259-260 ]. For example, the trial may look at whether the drug can reach the cancer and how cancer cells in people respond to the drug [ 259-260 ].

Phase 0 trials study a very small dose of a drug in a small number of people (usually fewer than 15 people) and last less than a week [ 259-260 ]. The dose of the drug is so small there’s no possible treatment benefit [ 259-260 ]. However, this also means the chance of side effects is low [ 260 ].

Although not common, phase 0 trials can be an important first step in human studies of a new drug treatment.

Breast cancer trials never use placebos instead of standard treatments

A placebo is an inactive substance sometimes used as a comparison to a drug in a clinical trial. Some people call this a “sugar pill.”

Some people worry they will get a placebo instead of an effective treatment in a clinical trial. Breast cancer trials never use a placebo instead of standard treatment. Sometimes, you may get standard treatment plus a placebo rather than standard treatment plus the new treatment that’s being studied.

Most often in a breast cancer treatment clinical trial, you’ll get either the new treatment or standard treatment. So, even if you don’t get the new drug (or other new therapy), your breast cancer will be treated the same as if you weren’t in the trial.

Your health care provider or the clinical research staff can tell you if there’s a placebo (in addition to standard treatment) in the study.

Benefits of clinical trials

If you have breast cancer, we encourage you to join a clinical trial. Clinical trials offer the chance to try new treatments and possibly benefit from them (except for phase 0 trials).

Learning a new therapy is better than the standard of care can also help others in the future. New therapies can help lead to other drugs and procedures that may be even more effective.

Possible drawbacks of clinical trials

Eligibility.

All clinical trials have criteria for joining the study, so you may not be eligible for a trial. Or there may not be a clinical trial currently enrolling people that’s right for you.

Learn more about eligibility for clinical trials .

Where you live may be a factor in choosing to join a clinical trial.

Some clinical trials are done in one, or only a few, medical centers. Others are done in many places across the country.

There may not be a clinical trial that’s right for you in your area. So, you may have to travel if you want to join.

Learn about programs that offer transportation and lodging assistance during treatment .

Side effects

The risks of a new treatment may not be fully understood, so there may be unexpected side effects.

All the side effects of a new treatment are often not known until after long-term testing and follow-up.

Extra tests or scans

Clinical trials often require more blood tests and imaging tests, such as X-rays or other scans, than standard treatment. This means you’ll have extra visits to the medical center for the tests.

Financial issues

The cost of the new treatment or test is usually paid by the clinical trial.

Out-of-pocket costs for most clinical trials are the same as those for standard treatment. If the cost of the drug therapy is covered by the clinical trial, out-of-pocket treatment costs may be lower for someone in the clinical trial.

However, there may be extra costs if the trial is in a different medical center. For example, you may have to pay more for travel or parking. A few clinical trials may cover transportation costs.

The Affordable Care Act  requires insurance companies to cover non-research, standard care costs related to a clinical trial (that aren’t covered by the trial itself) plus any standard treatment given.

Before enrolling in a clinical trial, talk with your insurance company to find out which costs are covered and which aren’t. This makes sure you don’t have any unexpected costs, such as out-of-network fees. Many cancer centers have financial counselors who can discuss insurance and cost coverage with you.

Clinical trials at the Clinical Center of the National Institutes of Health (NIH) in Bethesda, MD are free of charge to those who are eligible to join. For more information, visit the NIH clinical center website or call 1-800-4CANCER.

Learn about financial assistance .

Who can join a clinical trial

All clinical trials have eligibility criteria. These are the guidelines for who can join the study.

For example, each trial will have a list of medical conditions people must have (or not have) to join the study.

Clinical trials aren’t just for people who are undergoing cancer treatment. There are clinical trials for people who have finished treatment and for those who’ve never had breast cancer.

Learn more about eligibility criteria .

People who have breast cancer

If you have breast cancer, we encourage you to join a clinical trial. Clinical trials offer the chance to try new treatments and possibly benefit from them.

Learn about when to join a clinical trial .

People who’ve finished breast cancer treatment

Clinical trials for people who’ve completed breast cancer treatment study topics such as the long-term effects of treatments or the survival benefits of lifestyle behaviors (for example, diet and exercise).

Learn more about ways to get involved in breast cancer research .

People never diagnosed with breast cancer

Some clinical trials focus on non-treatment areas of breast cancer, such as risk reduction and screening. These studies often enroll people who’ve never had breast cancer to take part in the study. 

When to consider joining a clinical trial

If you’re newly diagnosed with breast cancer, consider joining a clinical trial before starting treatment.

Early breast cancer

For most people with early breast cancer, treatment doesn’t start right after diagnosis. So, there’s time to look for a clinical trial.

Once you’ve begun standard treatment for early breast cancer, it may be hard to join a clinical trial. For example, once you begin treatment, you can’t join a trial of neoadjuvant (before surgery) therapy, since neoadjuvant therapy would be a first treatment.

Breast cancer recurrence

If you have a breast cancer recurrence, consider joining a clinical trial before treatment for the recurrence begins or when your health care provider is considering changing treatments.

Metastatic breast cancer

If you’re diagnosed with metastatic breast cancer, consider joining a clinical trial when your health care provider is considering changing treatments or before starting a new treatment.

Sometimes, a clinical trial is available as the first treatment for metastatic breast cancer. If you haven’t started treatment yet, now is a good time to talk with your oncologist about clinical trials.

Talking with your health care provider and clinical trial staff

Before joining a clinical trial, discuss the risks and benefits with your health care provider.

There may be a research nurse or coordinator from the clinical trial who can give you more information about the study. See below for questions you may want to ask your health care provider and/or the research staff about joining a clinical trial .

Talking with friends and family may also be helpful in your decision-making process.

Eligibility for clinical trials

All clinical trials have guidelines (eligibility criteria) for who can join the study.

Criteria vary from study to study and may be based on:

• Type and stage of breast cancer
• Past treatments for breast cancer
• Other medical conditions

It’s important to find a clinical trial that fits your needs. However, clinical trials are designed for select groups of people. So, there may not be a trial that’s a good fit. For example, there may not be a clinical trial for people with your type of breast cancer and your past treatments for breast cancer.

How to enroll in a clinical trial

If you’ve found a clinical trial that’s right for you, your health care provider can put you in touch with a research nurse or coordinator from the trial.

This person will guide you through the enrollment process.  

Informed consent and clinical trials

Informed consent is the process in which a member of the study team reviews the purpose, risks, benefits and options for the study with you. It’s required for all clinical trials.

If you decide to join the study, you’ll be asked for your written permission.

The document you sign is called a consent form. You’ll get a copy for your records. This form includes the study protocol as well as the potential risks and benefits of the treatment or test.

Before joining a clinical trial, a research coordinator or nurse will go over the study protocol with you. This is part of the informed consent process. You may have a family member or friend with you.

The study protocol describes in detail:

• Reason/rationale for the study
• Study design
• Treatment regimen (what drugs or other therapies will be used)
• What tests will be done and how often the tests will be done
• What information (and any blood or tissue samples) will be collected
• How many people will be in the study
• Eligibility criteria (guidelines for who can join the study)

A consent form is usually a long document and can feel overwhelming. However, the research coordinator or nurse will answer any questions you have.

You’ll have time to review the consent form at home and consider your other treatment options before you make a decision on joining the trial. You may want to discuss your options with your family and other loved ones. Like all aspects of cancer care, the decision to join a clinical trial is a personal one.

Remember, being in a clinical trial is voluntary. You can leave the trial at any time, for any reason. Consenting and giving your written permission to join the study doesn’t force you to stay in the study.

The U.S. Food and Drug Administration (FDA) has a glossary of words you may see on a consent form or other materials related to clinical trials .

Questions you may want to ask the clinical trial research team

Before joining a clinical trial, talk with the research coordinator, nurse or physician from the study. This person can answer your questions and discuss any concerns you have.

You may want to take a friend or family member with you to help ask questions, take notes and give you support.

You may also ask your health care provider if you can record the discussion so you can review it later.

If English is not your preferred language, ask for a medical translator .

It’s a good idea to bring a list of questions and concerns. The following questions may be useful for your discussion.

• Why is this study being done? What is the potential impact of the study results?
• Who is funding this study?
• Can I join? How long do I have to decide about joining?
• What are the potential benefits and risks of joining this clinical trial? What benefits and risks are most likely for me?
• What were the results of other studies on this treatment or technique?
• Who chooses which type of treatment or procedure I will have?
• What are my chances of getting the new treatment or procedure?
• Is there a chance I’ll get a placebo?
• What tests or treatments are involved?
• How do the tests and treatments in this study compare to those with standard treatment?
• How often do I need to come in for treatment and testing? What kinds of tests will be done? How many extra visits and tests will be needed? Will the results of the tests be shared with me?
• How will you know if the treatment is working?
• What medical expenses will be paid by the clinical trial? Will my insurance cover the remaining costs or will I need to pay for them myself? Who can help answer any questions from my insurance company?
• Where is this study being done? Do I have to travel to participate? Should someone come with me to treatments and follow-up visits?
• Will costs such as travel and parking be covered?
• How long will I be in the study?
• What happens when the study ends? Is there long-term follow-up care? If the treatment is working for me, can I continue to get it after the study ends?
• What happens if I’m harmed somehow in the study? Is medical care provided and paid for by the study?
• Is there a person already enrolled in the study who I can talk with?
• How will I be told about the results of the study? How will the results be used or shared?
• How will my personal information be protected in this study?
• Who can I contact if I have more questions during or after the trial?
• Are there other clinical trials I should consider that might offer more benefit for me?

(Adapted from National Cancer Institute materials [ 261 ]).

If you’ve been recently diagnosed with breast cancer or feel too overwhelmed to know where to begin to gather information, Susan G. Komen® has a Questions to Ask Your Doctor About Clinical Trials resource that might help.

You can download and print it to take with you to your next doctor’s appointment or you can save it on your computer, tablet or phone using an app such as Adobe. Plenty of space and a notes section are provided to write or type the answers to the questions.

There are other Questions to Ask Your Doctor resources on many different breast cancer topics you may wish to download.

Who funds clinical trials

The National Cancer Institute (NCI), a government agency, funds many clinical trials for cancer.

The NCI also sponsors groups that study the same cancer topic, such as the American College of Radiology Imaging Network. These groups include hospitals, universities and doctors who work together to study cancer issues.

The Department of Defense and the Department of Veterans Affairs are other government sources of funding for clinical trials.

Pharmaceutical and biotechnology companies and nonprofit organizations also fund clinical trials.

Where to find a clinical trial

BreastCancerTrials.org in collaboration with Komen offers a custom matching service to help find clinical trials that fit your needs.

Internet resources

The websites below offer information on clinical trials and help in finding a clinical trial.

BreastCancerTrials.org www.breastcancertrials.org

CenterWatch clinical trials listing service www.centerwatch.com/

National Cancer Institute (NCI) clinical trials website www.cancer.gov/about-cancer/treatment/clinical-trials

National Institutes of Health (NIH) clinical trials websites www.cc.nih.gov/ www.clinicaltrials.gov/

Metastatic Trial Search

For people diagnosed with metastatic breast cancer, BreastCancerTrials.org in collaboration with Komen offers a web-based personalized clinical trial matching tool – the Metastatic Trial Search .

Komen Perspectives

Read our perspective on clinical trials.*

Other types of research studies

Clinical trials offer the chance to try new treatments that may be more effective than standard treatments.

Other types of studies, such as cohort studies and case-control studies , don’t offer a possible treatment benefit, but they increase our understanding about breast cancer in many ways. For example, they help us learn about risk factors and survivorship. 

Learn more about different types of research studies .

* Please note, the information provided within Komen Perspectives articles is only current as of the date of posting. Therefore, some information may be out of date. 

Updated 04/09/24

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You may be offered the opportunity to take part in a clinical trial at some point during your treatment for breast cancer. Clinical trials are research studies that evaluate the safety and effectiveness of new treatment approaches for diseases. In some cases, a study may give you access to new therapies that are not yet readily available.

Sometimes we use clinical trials to compare diagnostic tests, prevention strategies, or other aspects of care. We only conduct trials that we believe may improve some aspect of treatment and outcomes. You should always discuss the pros and cons of participating in a clinical trial with your doctor.  

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Should All Patients With Early Breast Cancer Receive Adjuvant Radiotherapy?

August 22, 2024

Adjuvant radiotherapy reduces the risk for short-term recurrence in patients with early breast cancer, but it may have no impact on long-term recurrence or overall survival, based on a 30-year follow-up of the Scottish Breast Conservation Trial.

These findings suggest that patients with biology predicting late relapse may receive little benefit from adjuvant radiotherapy, lead author Linda J. Williams, PhD , of The University of Edinburgh, Edinburgh, Scotland, and colleagues, reported.

"During the past 30 years, several randomized controlled trials have investigated the role of postoperative radiotherapy after breast-conserving surgery for early breast cancer," the investigators wrote in The Lancet Oncology . "These trials showed that radiotherapy reduces the risk of local recurrence but were underpowered individually to detect a difference in overall survival."

How Did the Present Study Increase Our Understanding of the Benefits of Adjuvant Radiotherapy in Early Breast Cancer?

The present analysis included data from a trial that began in 1985, when 589 patients with early breast cancer (tumors ≤ 4 cm [T1 or T2 and N0 or N1]) were randomized to receive either high-dose or no radiotherapy, with final cohorts including 291 patients and 294 patients, respectively. The radiotherapy was given 50 Gy in 20-25 fractions, either locally or locoregionally.

Estrogen receptor (ER)–positive patients (≥ 20 fmol/mg protein) received 5 years of daily oral tamoxifen. ER-poor patients (< 20 fmol/mg protein) received a chemotherapy combination of cyclophosphamide, methotrexate, and fluorouracil on a 21-day cycle for eight cycles.

Considering all data across a median follow-up of 17.5 years, adjuvant radiotherapy appeared to offer benefit, as it was associated with significantly lower ipsilateral breast tumor recurrence (16% vs 36%; hazard ratio [HR], 0.39; P < .0001).

But that tells only part of the story.

The positive impact of radiotherapy persisted for one decade (HR, 0.24; P < .0001), but risk beyond this point was no different between groups (HR, 0.98; P = .95).

"[The] benefit of radiotherapy was time dependent," the investigators noted.

What's more, median overall survival was no different between those who received radiotherapy and those who did not (18.7 vs 19.2 years; HR, 1.08; log-rank P = .43), and "reassuringly," omitting radiotherapy did not increase the rate of distant metastasis.

How Might These Findings Influence Treatment Planning for Patients With Early Breast Cancer?

"The results can help clinicians to advise patients better about their choice to have radiotherapy or not if they better understand what benefits it does and does not bring," the investigators wrote. "These results might provide clues perhaps to the biology of radiotherapy benefit, given that it does not prevent late recurrences, suggesting that patients whose biology predicts a late relapse only might not gain a benefit from radiotherapy."

Gary M. Freedman, MD , chief of Women's Health Service, Radiation Oncology, at Penn Medicine, Philadelphia, offered a different perspective.

"The study lumps together a local recurrence of breast cancer — that is relapse of the cancer years after treatment with lumpectomy and radiation — with the development of an entirely new breast cancer in the same breast," Freedman said in a written comment. "When something comes back between years 0-5 and 0-8, we usually think of it as a true local recurrence arbitrarily, but beyond that they are new cancers."

He went on to emphasize the clinical importance of reducing local recurrence within the first decade, noting that "this leads to much less morbidity and better quality of life for the patients."

Freedman also shared his perspective on the survival data.

"Radiation did reduce breast cancer mortality very significantly — death from breast cancers went down from 46% to 37%," he wrote ( P = .054). "This is on the same level as chemo or hormone therapy. The study was not powered to detect significant differences in survival by radiation, but that has been shown with other meta-analyses."

Are Findings From a Trial Started 30 Years Ago Still Relevant Today?

"Clearly the treatment of early breast cancer has advanced since the 1980s when the Scottish Conservation trial was launched," study co-author Ian Kunkler, FRCR , of The University of Edinburgh, said in a written comment. "There is more breast screening, attention to clearing surgical margins of residual disease, more effective and longer periods of adjuvant hormonal therapy, reduced radiotherapy toxicity from more precise delivery. However, most anticancer treatments lose their effectiveness over time."

He suggested that more trials are needed to confirm the present findings and reiterated that the lack of long-term recurrence benefit is most relevant for patients with disease features that predict late relapse, who "seem to gain little from adjuvant radiotherapy given as part of primary treatment."

Kunkler noted that the observed benefit in the first decade supports the continued use of radiotherapy alongside anticancer drug treatment.

When asked the same question, Freedman emphasized the differences in treatment today vs the 1980s.

"The results of modern multidisciplinary cancer care are much, much better than these 30-year results," Freedman said. "The risk for local recurrence in the breast after radiation is now about 2%-3% at 10 years in most studies."

He also noted that modern radiotherapy techniques have "significantly lowered dose and risks to heart and lung" compared with techniques used 30 years ago.

"A take-home point for the study is after breast conservation, whether or not you have radiation, you have to continue long-term screening mammograms for new breast cancers that may occur even decades later," Freedman concluded.

How Might These Findings Impact Future Research Design and Funding?

"The findings should encourage trial funders to consider funding long-term follow beyond 10 years to assess benefits and risks of anticancer therapies," Kunkler said. "The importance of long-term follow-up cannot be understated."

This study was funded by Breast Cancer Institute (part of Edinburgh and Lothians Health Foundation), PFS Genomics (now part of Exact Sciences), The University of Edinburgh, and NHS Lothian. The investigators reported no conflicts of interest.

Send comments and news tips to [email protected] .

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Clinical trials

If you're interested in taking part in breast cancer research, you can learn more about clinical trials here, including what they are, the benefits and potential drawbacks, and how to take part.

In this section

1. what are clinical trials.

Clinical trials are research studies involving people. They aim to improve diagnosis, treatment, side effects and quality of life.

For people with breast cancer, clinical trials might include:  

• Looking at ways to reduce the likelihood of getting breast cancer
• Improving diagnostic methods (such as breast screening)
• Testing new cancer drugs to find out more about them and any side effects
• Testing new treatments to see if they work better than current treatments
• Testing current treatments in different ways to reduce side effects
• Finding new ways to combine treatments to see if they work better
• Looking at the effect a treatment has on everyday life (quality of life)
• Looking at whether additional psychological support makes a difference

Find out more about clinical trials for breast cancer and the types of clinical trial you may be offered on the Cancer Research UK website.

2. Benefits and drawbacks of taking part in a clinical trial

Benefits of taking part in a clinical trial might include:

• Being one of the first people to benefit from a new treatment
• Having the opportunity to help others and improve breast cancer treatment
• Having extra appointments and tests which may mean you feel more supported and closely monitored

Drawbacks of taking part in a clinical trial might include:

• Unexpected side effects from a new treatment or an existing treatment given in a different way
• The new treatment not being any more effective than the standard treatment
• The new treatment being effective for some, but not for you
• Extra hospital visits that may not be convenient or desirable
• Extra tests that make you feel more nervous
• Not receiving the new treatment if you are part of the standard treatment (control) group of the trial

3. How are clinical trials approved?

New cancer drugs or treatments are tested and researched thoroughly before they are used in people.

Before a clinical trial begins it has to be approved by a group of independent scientists and then by a research ethics committee. The committee make sure the trial is safe and in the best interest of patients. They are made up of healthcare professionals as well as people without a medical background.

There are other safeguards in place for people taking part in trials. For example:

• The trial plan (protocol) must be judged safe and ethical by the ethics committee before it can go ahead
• The researchers must tell the ethics committee if there are any unexpected side effects
• The ethics committee can stop the trial at any time if they have any concerns
• Arrangements must be in place to pay compensation if anything goes wrong
• You must be told any benefits and risks before you agree to take part
• You can stop taking part in the trial at any time

If during a trial it becomes clear that one treatment is much better or worse than the other, or a treatment is causing severe side effects, the trial will be stopped and eligible patients will be offered the most effective treatment.

4. Phases of clinical trials

Clinical trials testing new treatments are divided into different phases. Phases 0 to 2 usually look at whether a drug is safe and any side effects it causes. Phases 3 and 4 aim to test whether a new treatment is better than existing treatments.

Phase 4 trials are carried out after a drug has been licensed (this link takes you to the Cancer Research UK website) . They look at drugs which are already available for doctors to prescribe rather than new drugs that are being developed.

You may be asked to join a phase 0 trial, although most trials involving cancer patients start at phase 1.

Find out more about the different phases of clinical trials on the Cancer Research UK website.

5. Can I take part in a clinical trial?

Your specialist may offer you the opportunity to take part in a clinical trial if you’re eligible. Or you could ask them about a trial you would like to take part in, or if there are any others that may be suitable for you. 

If you’re interested in taking part in a trial, talk it through with your specialist. They’ll be aware of the main breast cancer trials that are in progress and which ones are happening in your area. They can advise you according to your situation.

Every clinical trial has strict guidelines about who can be involved. For example, you might need to have a certain level of fitness to take part.

If you’re not able to take part in a particular trial, you may be disappointed. However, your treatment team will continue to support you and offer the best treatment and care available.

If you’ve been asked to take part

Deciding whether to take part in a clinical trial can be difficult and sometimes feel overwhelming.

If you’ve been asked to take part in a trial, your specialist or a research nurse will discuss exactly what’s involved with you. You should be given written information with all the details of the trial. This should include information about the type of trial, the possible benefits and risks, and whether extra tests or hospital appointments are needed. All information about participants is kept confidential.

You should be given time to make a decision about whether to take part.

It is important you understand what is involved before you give consent to take part. Ask your specialist or the research nurse any questions you may have. If you don’t feel that taking part in a trial is the right option for you, you can decline without giving a reason.

Questions to ask

You might like to ask some of the following questions if they’re not already covered in the information given to you by the trial team.

Some people find it useful to write a list of questions they want to ask and take it to their appointment. You can print off our list of suggested questions to take with you.

Giving consent

Once the details of the trial have been explained, you should be given written information and time to think it over and make your decision.

If you decide to take part in a clinical trial, you will be asked to sign a form saying that you agree to take part and understand what is involved. This is called giving informed consent. However, this does not commit you in any way and you can withdraw from the trial at any time if you change your mind.

If you’re thinking of leaving a trial you can do so at any time and you do not have to give a reason. Stopping taking part will not affect any future care you receive. If you want to leave a trial you can discuss this with your specialist or research nurse.

You cannot be entered into a clinical trial without your knowledge and without giving your consent.

Blood and tissue samples

You will have blood and tissue samples taken during your diagnosis and treatment. For example you may have tissue removed during a biopsy.

Your specialist may ask for your consent to use your samples for research. These samples can be looked at to:

• Find out more about different types of breast cancers
• Develop new breast cancer treatments or drugs

6. Where can I find out more about clinical trials?

You can find out more about clinical trials on the NHS website . Cancer Research UK also has information about clinical trials for breast cancer.

For current breast cancer clinical trials, you can search Cancer Research UK's online database or the  Be Part of Research website .

You’ll find research projects and clinical trial opportunities on our forum .

People living with secondary breast cancer can find clinical trials through Make 2nds Count's Patient Trials Advocate Service . The service matches people living with secondary breast cancer with a nurse who can talk you through the process and help you find clinical trials. 

You could also ask a member of your treatment team if they know about any clinical trials that you might be able to take part in.

7. Further support

Deciding whether to take part in a clinical trial can be overwhelming and you may feel unsure about the right option for you.

Speak to people who have been through similar experiences on our confidential forum . Our Someone Like Me service - please see below - can put you in touch with someone who has had a similar experience, so you can talk through your worries and share experiences over the phone or by email.

You can listen to other people’s experiences of clinical trials on the Healthtalk website.

If you would like any further information and support about clinical trials for breast cancer or just want to talk things through, you can speak to one of our experts by calling our free helpline, below.

Was this helpful?

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Last reviewed in November 2021. The next planned review begins in November 2023.

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Manuka Honey Reduces Breast Tumor Growth in Animal Model, Preliminary Study Finds

A new study suggests that manuka honey could potentially be an alternative, natural option for breast cancer treatment..

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A new study led by investigators at the   UCLA Health Jonsson Comprehensive Cancer Center  found that Manuka honey could potentially be an alternative, natural option for breast cancer  prevention and treatment —  particularly for estrogen receptor (ER)-positive breast cancer, the most common subtype of breast cancer that accounts for about 70–80% of all breast cancer cases.

In preclinical experiments, researchers found:

• Manuka honey significantly reduced tumor growth in mice with ER-positive breast cancer cells by 84% without affecting normal breast cells or causing major side effects.
• Higher concentrations of Manuka honey led to a greater reduction in cancer cell growth.
• Manuka honey reduced levels of signaling pathways that are upregulated in cancer such as AMPK/AKT/mTOR and STAT3, which are involved in tumor cell growth and survival.
• Manuka honey reduced the proliferation of cancer cells but did not affect the growth of normal human mammary epithelial cells, indicating it might target cancer cells specifically.
• Manuka honey induced apoptosis or cell death of breast cancer cells.
• The Manuka honey enhances the effectiveness of existing treatments such as tamoxifen, a commonly used antiestrogen drug in ER-positive breast cancer therapy, when used to together.

There is an urgent need for alternative treatments to help prevent the development of endocrine resistance and improve long-term breast cancer survival. Endocrine resistance is a major factor contributing to breast cancer being the leading cause of cancer-related deaths among women worldwide. New research has shown that Manuka honey, long known for its antimicrobial and antioxidant properties, is also rich in compounds like flavonoids, phytochemicals, complex carbohydrates, vitamins, amino acids, and minerals.

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To understand the potential of Manuka honey as a natural treatment for breast cancer, the research team conducted a series of experiments in mice and in ER-positive MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines, which represent two of the most common types of breast cancer. In these models, oral administration of Manuka honey resulted in a significant reduction in tumor growth compared to control groups. This significant inhibition of tumor progression underscores the honey's potential effectiveness as a treatment for cancer prevention or treatment.

The findings suggests that Manuka honey could potentially be developed into a natural supplement or even a standalone treatment for ER-positive breast cancer, particularly for patients who experience resistance to traditional therapies.

“The findings provide hope for development of a natural, less toxic alternative to traditional chemotherapy,” said  Dr. Diana Marquez-Garban , associate professor of medicine at the David Geffen School of Medicine at UCLA, and the study’s first author. “Although more research is necessary to fully understand the benefits of natural compounds in cancer therapy, this study establishes a strong foundation for further exploration in this area.”

Reference:  Márquez-Garbán DC, Yanes CD, Llarena G, et al. Manuka honey inhibits human breast cancer progression in preclinical models. Nutrients . 2024;16(14):2369. doi: 10.3390/nu16142369

This article has been republished from the following materials . Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here .

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For medical questions, we encourage you to review our information with your doctor.

Treating Breast Cancer

If you’ve been diagnosed with breast cancer, your cancer care team will discuss your treatment options with you. It’s important that you think carefully about each of your choices and weigh the benefits of each treatment option against the possible risks and side effects.

Local treatments

Some treatments, like surgery and radiation, are  local , meaning they treat the tumor without affecting the rest of the body. 

Most women with breast cancer will have some type of surgery to remove the tumor. Depending on the type of breast cancer and how advanced it is, you might need other types of treatment as well, either before or after surgery, or sometimes both.

• Surgery for Breast Cancer
• Radiation for Breast Cancer

Systemic treatments

Drugs used to treat breast cancer are considered  systemic therapies  because they can reach cancer cells almost anywhere in the body. Some can be given by mouth, injected into a muscle, or put directly into the bloodstream. Depending on the type of breast cancer, different types of drug treatment might be used, including:

• Chemotherapy for Breast Cancer
• Hormone Therapy for Breast Cancer
• Targeted Drug Therapy for Breast Cancer
• Immunotherapy for Breast Cancer

Common treatment approaches

Typically, treatment is based on the type of breast cancer and its stage. Other factors, including your overall health, menopause status, and personal preferences are also taken into account.

• Treatment of Breast Cancer by Stage
• Treatment of Triple-negative Breast Cancer
• Treatment of Inflammatory Breast Cancer
• Treating Breast Cancer During Pregnancy

Who treats breast cancer?

Based on your treatment options, you might have different types of doctors on your treatment team. These doctors could include:

• A breast surgeon or surgical oncologist: a doctor who uses surgery to treat breast cancer
• A radiation oncologist: a doctor who uses radiation to treat cancer
• A medical oncologist: a doctor who uses chemotherapy, hormone therapy, immunotherapy, and other medicines to treat cancer
• A plastic surgeon: a doctor who specializes in reconstructing or repairing parts of the body

You might have many other specialists on your treatment team as well, including physician assistants (PAs), nurse practitioners (NPs), nurses, psychologists, nutritionists, social workers, patient/nurse navigators, and other health professionals. 

• Health Professionals Who Are Part of a Cancer Care Team

Making treatment decisions

It’s important to discuss all of your treatment options, including their goals and possible side effects, with your doctors to help make the decision that best fits your needs. It’s also very important to ask questions if there's anything you’re not sure about. 

If time permits, it is often a good idea to seek a second opinion. A second opinion can give you more information and help you feel more confident about the treatment plan you choose.

• Questions to Ask Your Doctor About Breast Cancer
• Breast Reconstruction Surgery
• Seeking a Second Opinion

Connect with a breast cancer survivor

Reach to recovery, thinking about taking part in a clinical trial.

Clinical trials are carefully controlled research studies that are done to get a closer look at promising new treatments or procedures. Clinical trials are one way to get state-of-the art cancer treatment. In some cases they may be the only way to get access to newer treatments. They are also the best way for doctors to learn better methods to treat cancer. 

If you would like to learn more about clinical trials that might be right for you, start by asking your doctor if your clinic or hospital conducts clinical trials. 

• Clinical Trials

Considering complementary and alternative methods

You may hear about alternative or complementary methods to relieve symptoms or treat your cancer that your doctors haven’t mentioned. These methods can include vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to name a few.

Complementary methods are treatments that are used along with your regular medical care. Alternative treatments are used instead of standard medical treatment. Although some of these methods might be helpful in relieving symptoms or helping you feel better, many have not been proven to work. Some might even be harmful.

Be sure to talk to your cancer care team about any method you are thinking about using. They can help you learn what is known (or not known) about the method, which can help you make an informed decision. 

• Complementary and Integrative Medicine

Help getting through cancer treatment

People with cancer need support and information, no matter what stage of illness they may be in. Knowing all of your options and finding the resources you need will help you make informed decisions about your care.

Whether you are thinking about treatment, getting treatment, or not being treated at all, you can still get supportive care to help with pain or other symptoms. Communicating with your cancer care team is important so you understand your diagnosis, what treatment is recommended, and ways to maintain or improve your quality of life. 

Different types of programs and support services may be helpful, and they can be an important part of your care. These might include nursing or social work services, financial aid, nutritional advice, rehab, or spiritual help.

The American Cancer Society also has programs and services - including rides to treatment,  lodging, and more - to help you get through treatment. Call our Cancer Knowledge Hub at 1-800-227-2345 and speak with one of our caring, trained cancer helpline specialists. Or, if you prefer, you can use our chat feature on cancer.org to connect with one of our specialists.

• Palliative Care
• Programs & Services

Choosing to stop treatment or choosing no treatment at all

For some people, when treatments have been tried and are no longer controlling the cancer, it could be time to weigh the benefits and risks of continuing to try new treatments. Whether or not you continue treatment, there are still things you can do to help maintain or improve your quality of life.

Some people, especially if the cancer is advanced, might not want to be treated at all. There are many reasons you might decide not to get cancer treatment, but it’s important to talk to your doctors as you make that decision. Remember that even if you choose not to treat the cancer, you can still get supportive care to help with pain or other symptoms.

• If Cancer Treatments Stop Working

The treatment information given here is not official policy of the American Cancer Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor. Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask your cancer care team any questions you may have about your treatment options.

More in Breast Cancer

• About Breast Cancer
• Risk and Prevention
• Early Detection and Diagnosis
• Understanding a Breast Cancer Diagnosis
• Living as a Breast Cancer Survivor

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Polycystic ovary syndrome and risk of breast cancer in premenopausal and postmenopausal women: a nationwide population-based cohort study

• Published: 21 August 2024

Cite this article

• Clarissa L. B. Frandsen   ORCID: orcid.org/0000-0003-0956-9765 1 , 2 ,
• Bugge Nøhr   ORCID: orcid.org/0009-0009-9744-4452 2 ,
• Mathilde Gottschau   ORCID: orcid.org/0000-0002-3524-2646 1 ,
• Jakob H. Viuff   ORCID: orcid.org/0000-0002-5370-2589 3 ,
• Thomas Maltesen   ORCID: orcid.org/0000-0002-3988-2456 4 ,
• Susanne K. Kjær   ORCID: orcid.org/0000-0002-8347-1398 1 , 5 ,
• Pernille F. Svendsen   ORCID: orcid.org/0000-0002-8534-7868 2 &
• Allan Jensen   ORCID: orcid.org/0000-0001-8124-4880 1  

Although some reproductive and metabolic characteristics of polycystic ovary syndrome (PCOS) are known risk factors for breast cancer, the evidence regarding a potential association between PCOS and breast cancer is scarce. In this population-based cohort study including all 1,719,452 women born in Denmark between 1940 and 1993, we investigated the association between PCOS and breast cancer.

PCOS diagnoses, cancer diagnoses, covariates, migrations, and vital status were all obtained from national population and health registers. Hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer overall and for histological subtypes separately were calculated based on adjusted cox proportional hazards models.

During a median follow-up of 26 years, 63,078 women were diagnosed with breast cancer. We found an increased risk of breast cancer overall among women with PCOS compared with women without PCOS (HR: 1.21, 95% CI 1.02–1.44). In analyses stratified for menopausal status, the increased risk was restricted to postmenopausal women (HR: 1.63, 95% CI 1.23–2.15). The results for ductal and lobular histological subtypes analyses separately resembled those observed for breast cancer overall.

This is the first study to report an increased risk of breast cancer among women with a history of PCOS. The increased risk was seemingly confined to postmenopausal women. Our results therefore contribute to an increased knowledge of the etiology of breast cancer, but our findings should be further confirmed in other large cohort studies with an appropriately long follow-up period.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due to restrictions by the Danish General Data Protection Regulation. The data are pseudo-anonymized registry data available from Statistics Denmark, which were used under license for this study. Data are available from the authors upon reasonable request with the permission of Statistics Denmark and The Danish Health Data Authority.

Abbreviations

Confidence interval

Hazard ratio

Hormone therapy

International Classification of Diseases for Oncology, 3rd edition

International Classification of Diseases, 7th revision

International Classification of Diseases, 8th revision

International Classification of Diseases, 10th revision

Inter quartile range

Polycystic ovary syndrome

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This work was supported by internal grants from the Danish Cancer Institute and from the Department of Gynecology and Obstetrics, University Hospital of Herlev and Gentofte. The study also received a grant from Helsefonden (Grant No. 21-B-0261).

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Virus, Lifestyle and Genes, Danish Cancer Institute, Strandboulevarden 49, 2100, Copenhagen, Denmark

Clarissa L. B. Frandsen, Mathilde Gottschau, Susanne K. Kjær & Allan Jensen

Department of Obstetrics and Gynecology, University Hospital of Herlev and Gentofte, Copenhagen, Denmark

Clarissa L. B. Frandsen, Bugge Nøhr & Pernille F. Svendsen

Diet, Cancer and Health, Danish Cancer Institute, Copenhagen, Denmark

Jakob H. Viuff

Statistics and Data Analysis, Danish Cancer Institute, Copenhagen, Denmark

Thomas Maltesen

Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Susanne K. Kjær

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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Clarissa Lima Brown Frandsen, Jakob Hansen Viuff and Thomas Maltesen. The first draft of the manuscript was written by Clarissa Lima Brown Frandsen and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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The study was approved by The Danish Health Data Authority (J. no. FSEID-00005526) and Statistics Denmark (J. no. 708224) and approved and registered in the archive list of the Danish Cancer Institute (J. no. 2021-DCRC-0002). According to Danish law, an approval from the Ethical Committee is not required for this type of register-based study.

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Supplementary Figure 1. Directed acyclic graphs which supported the two different models used for main analyses: Model A) adjusted for birth year and highest achieved level of education (basic, medium, higher, missing) as a marker for socioeconomic status, and Model B) additionally adjusted for obesity (yes/no). Highest achieved level of education and obesity were defined at baseline

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Frandsen, C.L.B., Nøhr, B., Gottschau, M. et al. Polycystic ovary syndrome and risk of breast cancer in premenopausal and postmenopausal women: a nationwide population-based cohort study. Breast Cancer Res Treat (2024). https://doi.org/10.1007/s10549-024-07467-8

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DOI : https://doi.org/10.1007/s10549-024-07467-8

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• Published: 21 August 2024

Dipeptide PA3264 derived from rare and endangered Squama Manis is a novel bioactive peptide for the treatment of triple-negative breast cancer

• Xiaorong Hou 1 , 2 , 3 ,
• Zhaofang Bai 2 , 3 ,
• Yuanyuan Chen 1 , 2 , 3 ,
• Wei Shi 2 , 3 ,
• Huijie Yang 2 , 3 ,
• Ruisheng Li 4 ,
• Xiaoyan Zhan 2 , 3 ,
• Youping Liu 1 ,
• Xu Zhao 2 , 3 &
• Xiaohe Xiao 1 , 2 , 3  

Chinese Medicine volume  19 , Article number:  112 ( 2024 ) Cite this article

Metrics details

Squama Manis is a valuable traditional Chinese medicine with a long history of medicinal use in the treatment of breast-related diseases. However, owing to the excessive exploitation and utilization of the resources, Squama Manis has been included in the list of rare and endangered wild animals. The conservation of the resources of Squama Manis and continuing its clinical application has become an urgent problem, and the search for small-molecule substitutes for Squama Manis is an effective way to achieve this goal. Previous studies have identified PA3264 as a possible active ingredient in Squama Manis. In this study, we systematically investigated the pharmacological effects and mechanisms of PA3264 in the treatment of triple-negative breast cancer (TNBC), a representative breast-related disease.

Cell viability and colony formation assays were performed after treatment with the target dipeptide PA3264 in vitro. Next, 4T1 orthotopic tumors and humanized PBMC-CDX mouse models were generated to examine the antitumor effect of PA3264 in vivo. Transcriptome sequencing and molecular docking experiments were performed to predict pathways to function. Western blotting and quantitative real-time PCR were used to validate the molecular mechanisms underlying the anticancer effects of PA3264.

PA3264 significantly inhibited cell viability and migration of breast cancer cells in vitro. Furthermore, PA3264 suppressed the tumor size and reduced the tumor weight in vivo. Finally, it was verified that PA3264 prevented the progression of breast cancer by inhibiting the PI3K/AKT/NF-κB pathway, causing cell cycle arrest, and promoting apoptosis.

Conclusions

This study elucidated that PA3264 derived from rare and endangered Squama Manis was a novel bioactive peptide for treating triple-negative breast cancer from a scientific research perspective.

Introduction

Squama Manis (pangolin scale) from the scaly armor of Manis pentadactyla Linnaeus has a long history of medicinal use in traditional Chinese medicine. It was first recorded in the " Ming Yi Bie Lu " by Tao Hongjing of the Southern Dynasty and began to be known as “Chuan shanjia” in the classic works of Chinese medicine [ 1 ]. It has a salty flavor and is mildly cold. It has the function of activating blood and resolving mass, unblocking the meridian and promoting lactation, and dispersing swelling and expelling pus, et al. [ 2 ]. Squama Manis has been formulated as an ingredient of TCM prescriptions to treat patients with symptoms as amenorrhea, abdominal mass, inhibited lactation, abscess and sore, especially widely used in breast related diseases [ 3 ], including mastitis [ 4 ], breast hyperplasia [ 5 ], and breast cancer [ 6 ].

Owing to its significant food and medicinal value, Squama Manis has been subjected to destructive and indiscriminate hunting. Squama Manis is an exceptionally ecologically specialized monotypic order and family, which cannot be successfully reared and bred on a large scale commercially around the globe and can only be captured in the wild, thus leading to a drastic reduction in wild resources [ 7 ]. Squama Manis is one of the wild medicinal species protected under China's Regulations on the Protection and Management of Wild Medicinal Resources, which has been elevated from the second level of national critical protection to the first level since 2020 and has been classified as critically endangered by the International Union for Conservation of Nature (IUCN) Red List of Threatened Species [ 7 , 8 ]. Therefore, it was no longer included in the 2020 edition of the Chinese Pharmacopoeia. Although the clinical efficacy of Squama Manis is exact, it has attracted considerable attention both domestically and abroad because of its endangered resources. Hence, resource protection and the search for alternatives to Squama Manis with similar efficacies are of great significance.

A great deal of work has also been carried out on the chemical composition of Squama Manis and its pharmacological effects, including anticoagulant, antithrombotic, and antitumor [ 1 ]. It has been reported that cyclic dipeptides are the main active ingredients, and L-serine-L-tyrosyclic dipeptide, D-serine-L-tyrosyclic dipeptide, L-glycine-L-tyrosyclic dipeptide, and other constituents have been successfully isolated from Squama Manis [ 9 ]. The discovery of more active peptides for treating breast-related diseases and the exploration of their mechanisms need to be followed by further studies. Previous studies have identified a peptide, PA3264, as a possible active ingredient of Squama Manis, but its pharmacological activity in breast diseases is unknown.

Triple-negative breast cancer (TNBC), a typical breast disease, is an aggressive subtype of breast cancer with recurrence and metastasis and has a poor prognosis [ 10 ]. The PI3K/AKT pathway has been reported to be a frequent signaling pathway in TNBC, making it one of the most important signaling pathways for therapeutic intervention. In addition, abnormal activation of nuclear factor-κappa B (NF-κB) induces the expression of target genes that participate in cell cycle regulation, cell proliferation, and apoptosis [ 11 , 12 ]. Thus, inhibition of the PI3K/AKT pathway, as well as the downstream NF-κB pathway, contributes to antitumor effects. Here, a new linear dipeptide, PA3264, from Squama Manis, had a significant inhibitory effect on TNBC. Mechanistically, it inhibited the proliferation of breast cancer cells, caused cell cycle arrest, and promoted apoptosis by inhibiting the PI3K/AKT/NF-κB pathway. This study provides new ideas for the search for Squama Manis substitutes and the conservation of its resources. It provides a theoretical basis for a novel and effective leading compound, PA3264, for treating TNBC.

Materials and methods

D-Tyrosine-L-serine (PA3264) was synthesized and purified by GenScript Company (C216JHB100_5, NJ, USA). The HPLC purity was ≥ 98.0%. The peptide was soluble in ddH 2 O and stored at −20 °C. A patent application was filed for the compound (Chinese patent application for authorization No.: CN 114315958 B).

UPLC-MS/MS analysis of PA3264 from Squama Manis

Squama Manis was obtained from Fifth Medical Center of Chinese PLA General Hospital and identified by Xiaohe Xiao professor. A Vanquish Flex UPLC system (Thermo Scientific, MA, USA) interfaced with a Q Exactive Focus mass spectrometer (Thermo Scientific) was used for UPLC-MS/MS analysis [ 13 , 14 , 15 ]. The following UPLC condition was used: The chromatographic column a Thermo Scientific Accucore HILIC column (2.1 × 100 mm, 2.6 μm, Part No.: 17526–102130); and an eluent of 10 mM ammonium acetate in 10% acetonitrile (A) and 10 mM ammonium acetate in acetonitrile (B) with the following gradient elution system: 25% A and 75% B in 0–6 min, then 45% B in 6–7 min, 30% B in 7–10.1 min, 75% B in 10.1–22 min at an eluent flow rate of 0.3 mL/min. The column temperature was maintained at 40 °C. The total running time was 22 min. An injection volume of 5 μL was used for each sample. The optimized parameters of MS were as follows: Spray voltage, 3.8 kV; Aux gas heater temperature, 350 °C; Sheath gas flow rate, 45 arb; Aux gas flow rate, 15 arb; Capillary temperature, 320 °C; S-lens RF, 60 V; scan mode: (1) full MS: resolution: 70, 000; automatic gain control target: 1.0e6; maximum injection time: 100 ms; scan range: 133.4–2000 m/z; (2) dd-MS2: resolution: 17500; automatic gain control target: 1.0e5; maximum injection time: 50 ms; loop count: 3; isolation window: 2.0 m/z; NCE/stepped: 20 40 60; dynamic exclusion: 8 s.

Cell cultures

The breast cancer cell lines MDA-MB-231 and 4T1 were obtained from ATCC and maintained in high-glucose Dulbecco Modified Eagle Medium (DMEM) and RPMI 1640 medium supplemented with 100 U/mL penicillin, 100 µg/mL streptomycin (all from BOSTER, Beijing, China), and 10% fetal bovine serum (C04001-500, VivaCell, Beijing, China) in a humidified atmosphere of 5% CO 2 at 37 °C for serial passaging. The cells were harvested during the logarithmic growth phase for subsequent experiments. The cells were frozen in a serum-free cell freezing medium (03.17004DA, EallBio, Beijing EallBio Biomedical Technology Co., Ltd, China).

Female BALB/c mice (6–8 weeks old; 18–20 g) were purchased from SPF Biotechnology Co., Ltd. (Beijing, China) and housed in a standard pathogen-free (SPF) standard room. Six-week-old female supra-immunodeficient NCG-hIL15 mice were purchased from GemPharmatech (Jiangsu, China) and were maintained in microisolator cages under pathogen-free conditions. Laboratory animal production license: SCXY (Jing) 2019-0010, Laboratory animal production license: SCXK (Su) 2020–0004. All mice were given free access to standard laboratory chow and water ad libitum for the experiment with a 12-h light–dark cycle at a temperature of 21–25 °C. Protocols for animal experiments were approved by the guidelines for the care and use of laboratory animals. All experiments were performed under the approved guidelines of the Animal Ethics Committee of the Fifth Medical Center, Chinese PLA General Hospital (IACUC-2023-0014).

Tumor challenge and treatment experiments

4T1 orthotopic tumors were induced via subdermal inoculation of 2 × 10 5 4T1 early passage cells suspended in 100 μL of PBS into the 4th mammary fat pad of BALB/c females, as described previously [ 16 ]. At 1-week post-inoculation (tumors were palpable around 15 mm 3 ), the animals were randomly distributed into the control and treatment groups. PA3264 (100 mg/kg) was administered intraperitoneally (i.p.) once daily. Cisplatin (HY-17394, MedChemExpress, NJ, USA) was used as the positive control (2 mg/kg, once every 4 days) [ 17 ]. Animal body weight and tumor growth were measured three times per week. Tumor volume was calculated using the following equation: 0.5 × length × width 2 [ 18 ]. At the end of the experimental period, the mice were sacrificed, and the remaining tumors were harvested for weighing and other experiments.

The humanized PBMC-CDX mouse model was established previously [ 19 , 20 ]. MDA-MB-231 tumor cells were subcutaneously inoculated into tumor-donor mice. After the tumors grew, tumors with a volume of approximately 500–1000 mm 3 were removed under aseptic conditions, cut into tumor masses of approximately 8 mm 3 , and inoculated subcutaneously in the right flank of experimental mice with a cannula needle. Each mouse was injected with a tumor mass. Three days after tumor inoculation, healthy adult PBMCs were inoculated into the mice by resuspension in PBS at an inoculation rate of 2 × 10 6 /mouse. Tumors were administered in groups when they grew to approximately 50–70 mm 3 (Day10). PA3264 was intraperitoneally injected at a dose of 50 mg/kg for 21 days.

Histology and immunohistochemistry (IHC)

Tumor samples were fixed in 4% paraformaldehyde and then dehydrated and embedded with paraffin for H&E staining. Proteins in tumor tissues were also assessed by immunohistochemistry assay. Tissue sections (4 μm) were deparaffinized, rehydrated, and antigen-repaired. After blocking, anti-Ki67 (Abcam, ab16667, 1:100) and Caspase 3 (Bioss, bs-0081R, 1:100) were incubated overnight at 4 °C. The corresponding secondary antibody was incubated for 1 h. Finally, sections were stained with 3,3'-diaminobenzidine (DAB, BOSTER, AR1022), counter-stained with hematoxylin, dehydrated with gradient ethanol, cleared with xylene, sealed with neutral gum, observed, and photographed under an Eclipse microscope (Nikon Corporation). The proportion of positively stained area was analysed using Image J by calculating the positive areas in the total cells [ 21 , 22 ].

Transcriptome sequencing (RNA-seq) analysis

Total RNA was extracted from the samples and enriched with oligo (dT)-attached magnetic beads. The synthesized and purified double-stranded cDNA was subjected to end repair and 3'-adenylation. Sequencing adapters were connected to the ends of these 3′ adenylated cDNA fragments, and the selected fragments were amplified by PCR and qualified using an Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA, USA). Libraries were constructed using the VAHTS Universal V6 RNA-seq Library Prep Kit according to the manufacturer’s instructions after the quality inspection was completed. Sequencing was performed using Illumina HiSeqTM 2500. Differential expression analysis was performed using the DESeq2. A Q value < 0.05 and foldchange > 2 or foldchange < 0.5 was set as the threshold for significantly differentially expressed genes (DEGs). Transcriptome sequencing and analysis were performed by OE Biotech Co. Ltd. (Shanghai, China) using standard procedures.

Molecular docking

Molecular docking was performed using Schrödinger Suite Release 2018-1 [ 23 , 24 ]. PI3Kγ, AKT1, and NF-κB p65 proteins were used as receptors, and PA3264 was used as a ligand. Three-dimensional crystal structures of PI3Kγ (PDB ID: 4HVB), AKT1 (PDB ID: 4EKL), and NF-κB p65 (PDB ID: 1NFI) were retrieved from the RCBS PDB database. This structure was optimized before docking using Protein Preparation Wizard in Maestro 11.5. The docking of the receptor (target) preparation involves the deletion of water molecules from target proteins, removal of protein polymorphisms, complementation of non-complete amino acid residues, and hydrogenation of proteins, followed by lattice-box construction of each target protein. LigPrep was used to convert structures from 2-dimensional to 3-dimensional, correction improper bond distances and bond orders, generating ionization states, and minimizing energy. The processed protein and ligand structures were subjected to docking analysis. Finally, docking scores were calculated to evaluate the binding activity between the ligand and three targets. The display diagram of the molecular docking results was modified using PyMOL.

Cell viability assay

To assess the effects of PA3264 on cell viability, 1.5 × 10 5 MDA-MB-231 and 9.0 × 10 4 4T1 cells per well in 96 well plates were incubated for 12 h. The medium was then replaced with different PA3264 concentrations (0, 0.078, 0.156, 0.313, 0.625, 1.25, 2.5, 5, 10, and 20 mg/mL) for the indicated times. Cell viability was measured using the CCK-8 assay kit (G4103-5ML, Servicebio, Wuhan, China) according to the manufacturer’s instructions. The optical density (OD) values used as the index of cell viability were measured at 450 nm using a microplate reader, and the IC 50 values were calculated as described previously [ 21 ]. Lactate dehydrogenase (LDH) is a stable cytoplasmic enzyme in all cells. LDH is rapidly released into the cell culture supernatant when the plasma membrane is damaged, a key feature of cells undergoing apoptosis, necrosis, and other forms of cellular damage [ 25 ]. The LDH release assay was performed using the LDH Cytotoxicity Assay kit (G1610-100 T, Servicebio, Wuhan, China), according to the manufacturer's protocols.

Colony formation assay

To assess clonogenic ability, single cell suspensions containing 2 × 10 3 MDA-MB-231 and 4T1 cells were seeded in 12-well plates and allowed to adhere for 24 h, and treated with PA3264 for 5 days. The cells were fixed in 4% paraformaldehyde and stained with crystal violet. Finally, the colonies were quantified using the ImageJ software.

Wound healing assay

A total of 2 × 10 5 cells were seeded in the wells of a 12-well plate for 24 h. The cell layer was scratched using a sterile pipette tip (200 µL). Subsequently, cells were cultured with the indicated concentrations of PA3264. Representative images of the wounds were taken at 0 and 24 h using an Eclipse microscope (Nikon Corporation, Tokyo, Japan). Each experiment was conducted in triplicate.

Quantitative real-time PCR (qRT-PCR)

Total RNA was extracted using TRIzol reagent (Alcatel, Beijing, China), and the isolated RNA was reverse-transcribed into cDNA using StarScript III All-in-one RT Mix with gDNA Remover (GenStar, Beijing, China). Primer sequences used are listed in Table  1 . Quantitative real-time PCR was performed on a QuantStudio 6 (96-well format, Thermo Fisher, USA) using SYBR Green qPCR Master Mix (Low ROX) (GenStar, Beijing, China). The PCR conditions were as follows: 95 °C for 5 min, followed by 40 cycles of 95 °C for 10 s, and 60 °C for 60 s. The expression levels of these genes were normalized to that of β-actin. The data were analyzed and displayed using the ΔΔCt or 2 −ΔΔCt method.

Western blotting

Cell lysates were collected using RIPA buffer [50 mM Tris–HCl, 150 mM NaCl, 1% sodium deoxycholate, and 1% Triton-100, pH 7.45]. Protein denaturation was performed before loading at 100 °C for 15 min. Proteins were separated using 10% SDS-PAGE and transferred to PVDF membranes (Millipore Corp., Bedford, MA, USA). Membranes were then blocked with 5% skim milk for 1 h and exposed to the primary antibodies with an appropriate dilution at 4 °C overnight: p-PI3K (Abcam, ab278545,1: 1500), PI3K (ZENBIO, R22768, 1: 2000), p-AKT (Cell Signaling Technology, 4060 T, 1: 2000), AKT1 (HUABIO, ET1609-47, 1: 1500), p-p65 (Abcam, ab76302, 1: 1500), p65 (Cell Signaling Technology, 8242S, 1: 1000), Cyclin D1 (Abcam, ab134175, 1: 5000). HSP90 (ZENBIO, 251211, 1:2000) was used as the internal control. Membranes were subsequently probed with anti-mouse or anti-rabbit IgG antibodies conjugated to horseradish peroxidase (Transduction Laboratories, Lexington, KY, USA) and visualized using enhanced chemiluminescence (ECL, E422-02, Vazyme, Nanjing, China).

Quantification and statistical analysis

Two-tailed unpaired Student’s t-test was used to compare two groups. Multiple groups were tested using a one-way analysis of variance (ANOVA). Two-factor ANOVA was used for tumor growth analysis. All data are presented as mean ± SEM. Data were processed using GraphPad Prism version 9 (GraphPad Software). In all cases, p values of 0.05 and below were considered to be statistically significant: p  < 0.05 (*), p  < 0.01 (**), and p  < 0.001 (***) were considered statistically significant. Detailed information regarding the number of replicates can be found in the figure legend.

The extracted ion chromatogram of PA3264 from Squama Manis showed that its molecular formula of PA3264 was C12H16N2O5, with a theoretically calculated [M + H] + mass charge ratio (m/z) of 269.1132. The lower image characterized the possible structures of the two fragment ions in the mass chromatogram of PA3264 (Fig.  1 A). The mass spectral verification of the synthetic dipeptide PA3264 was shown in Fig.  1 B. The theoretically calculated [M + H] + mass-to-charge ratio (m/z) was 269.11289. One of the fragment ions matched the one shown in Fig.  1 A. The structure of PA3264 was roughly deduced from the molecular ion peaks and fragment ion results of PA3264 in Squama Manis and synthetic peptide samples. Next, we investigated the pharmacological activity and mechanism of action of PA3264 in breast-related diseases represented by triple-negative breast cancer.

UPLC-MS/MS analysis of PA3264 from Squama Manis. A The upper panel shows the extracted ion chromatogram of PA3264. The mass spectra of PA3264 are shown in the lower panel. B MS and MS/MS spectra of synthetic dipeptide PA3264

PA3264 restrained the viability and clonogenicity in murine and human-derived breast cancer cells

To explore the effect of PA3264 on the proliferation of murine and human breast cancer cells, CCK-8 and LDH release assays were used to determine the viability of 4T1 and MDA-MB-231 cells after treatment with various concentrations of PA3264 for 24 h. The results showed that the proliferation of 4T1 and MDA-MB-231 cells treated with PA3264 was significantly lower than that of the control group, in a dose-dependent manner (Figs.  2 A and 3 A). The LDH release assay showed that PA3264 treatment accelerated plasma membrane damage in breast cancer cells in a dose-dependent manner (Figs.  2 B and 3 B). In addition, colony formation assays showed a decrease in the number of colonies formed as the intervention concentration of PA3264 increased (Figs. 2 C, D and 3 C, D). These results indicated that PA3264 curbed the cell viability and colony formation of murine and human-derived breast cancer cells in a dose-dependent manner.

PA3264 inhibited the proliferation and migration of 4T1 cells. A Inhibition of 4T1 cell proliferation was assessed by the CCK-8 assay after 24 h of treatment with different concentrations of PA3264. B LDH was released from 4T1 cells after 24 h of treatment with different concentrations of PA3264. C Colony formation after treated with PA3264 at different concentrations (0, 1.25, 5, and 20 mM) using a plate cloning assay. D Quantitative histogram of the clone formation. E – F Representative images and results of wound healing assays with 4T1 cells treated with PA3264 (0, 20 mM) for 24 h. The figure shows the mean ± SEM of the experimental data for each group. * p  < 0.05, ** p  < 0.01, *** p  < 0.001 (versus the control group), n = 3

PA3264 significantly suppressed the viability of MDA-MB-231 cells. A MDA-MB-231 cells were treated with serial concentrations of PA3264, and the effects of PA3264 on cell proliferation were measured using the Cell Counting Kit-8 examinations at 24 h. B LDH was released from MDA-MB-231 cells after 24 h of treatment with different concentrations of PA3264. C – D Images and results of colony formation assay with MDA-MB-231 cells treated with PA3264. Data were presented as mean ± SEM, n = 3, * p  < 0.05, ** p  < 0.01, *** p  < 0.001 vs. the control group

PA3264 constrained the migration of 4T1 cells

To evaluate the effect of PA3264 on 4T1 cell migration, wound healing assays were performed. After 4T1 cells were incubated with 20 mM PA3264 for 24 h, the migration distance was significantly reduced by 39% compared with the control group (Fig.  2 E, F, p  < 0.05). The data demonstrated that PA3264 had a remarkable prevention on wound healing as an inhibitor of 4T1 cell migration.

PA3264 inhibited tumor growth in vivo

To examine the antitumor effects of PA3264 in vivo, 4T1 orthotopic tumors were constructed and treated. As shown in Fig.  4 A, B, tumor volume and weight in the model group increased more dramatically. At the same time, cisplatin and PA3264 treatments significantly inhibited the increase in tumor volume and weight as early as 4 weeks after injection. At the end of this period, the tumor volume and weight in PA3264-treated mice were reduced by 41% and 32%, respectively, compared to those in control mice ( p  < 0.01). Cisplatin used as a positive control had a significant depression effect on tumor size and weight. Strikingly, the treated groups had a smaller burden than the control group (Fig.  4 E). In addition, a humanized PBMC-CDX mouse model was used to validate the antitumor activity of the PA3264. Tumor volume was also reduced in mice treated with PA3264 for 24 consecutive days compared with the control group (Fig.  4 D, p < 0.01).

PA3264 inhibited tumor growth in vivo by inhibiting proliferation and inducing apoptosis. A PA3264 suppressed tumor growth in mice bearing 4T1 orthotopic tumors. B PA3264 decreased the tumor weight in mice bearing 4T1 orthotopic tumors. C The body weights of mice were checked every three days. Data were presented as the mean ± SEM (n = 7–9). D Growth curve of tumor volumes in humanized PBMC-CDX mouse model. Data were presented as mean ± SEM, n = 6. E Tumors of 4T1 cells treated with PA3264 or saline for 21 days were photographed. F Representative H&E-stained histological images of tumor sections. Scale bar: 10 nm, n = 5. G Representative histological images of tumor sections stained with Ki67 and Caspase 3 and quantitative analysis of their expression. Scale bar: 20 μm, n = 5. H Bax and Bcl-2 mRNA expression in tumor tissues was analyzed using quantitative real-time PCR. The ratio of Bax/Bcl-2 expression was also shown. Data were presented as mean ± SEM, n = 9. * p  < 0.05, ** p  < 0.01, *** p  < 0.001 vs. the control group

Body weight is one of the most important indicators for evaluating the safety of anticancer drugs. Throughout the experimental period, the body weight of mice treated with PA3264 did not change significantly compared with that of the control group (Fig.  4 C). However, the body weights of cisplatin-treated mice decreased significantly 3 weeks after injection compared with the control group (Fig.  4 C). Additionally, the effect of PA3264 on liver and renal function indicators in 4T1 tumor-bearing mice was investigated by measuring serum related biochemical parameters (ALT, AST, BUN, and CRE). Compared with the normal group, the serum BUN levels in the model group were significantly elevated ( p  < 0.01), indicating that the renal function of the tumor-bearing mice was damaged to a certain extent (Suppl. Figure 1C). After cisplatin treatment in the tumor-bearing mice, the levels of serum ALT, BUN, and CRE in the cisplatin group were significantly higher than those in the control group ( p  < 0.05, Suppl. Figure 1A, 1C, and 1D), while the levels of AST were also increased ( p  > 0.05, Suppl. Figure 1B), indicating that the liver and renal function of the tumor-bearing mice were damaged to a certain extent by cisplatin administration. After treatment with PA3264 in the tumor-loaded mice, the levels of ALT, AST, BUN, and CRE were lower than those in the model group, but the difference was not statistically significant ( p  > 0.05, Suppl. Figure 1A–D). Compared with the cisplatin group, the levels of ALT, BUN, and CRE in the PA3264-treated group were significantly decreased ( p  < 0.01, Suppl. Figure 1A, 1C, and 1D), while the levels of AST were also reduced. Still, the difference was not statistically significant ( p  > 0.05, Suppl. Figure 1B). This suggested that PA3264 did not significantly damage the liver and kidney function of the tumor-loaded mice. In summary, treatment with PA3264 and cisplatin was largely effective in regressing tumors and PA3264 was safer to administer in vivo than cisplatin.

The histology of tumor sections showed that tumor cells, which had apparent nucleoli and large nuclei, were arranged tightly in the control group. In contrast, there was a loose arrangement in the PA3264 treated group (Fig.  4 F). In addition, immunohistochemical staining of tumor tissues with Ki67 and Caspase 3 was performed. PA3264 administration decreased the expression of Ki67 and increased the expression of Caspase 3 in the tissues compared with the control group (Fig.  4 G). Quantitative real-time PCR analysis of tumor tissues showed that the expression of Bax and the Bax / Bcl-2 ratio was upregulated after PA3264 treatment (Fig.  4 H). Taken together, these in vivo data suggest that PA3264 inhibited the proliferation and promoted the apoptosis of triple-negative breast cancer.

Identification of DEGs and their pathways in PA3264-mediated tumor suppression by RNA-seq analysis

To explore the genes and pathways involved in inhibiting 4T1-induced triple-negative breast cancer by PA3264, RNA from the four replicate samples from the control and PA3264-treated groups were sequenced. Cutoff values were set at |log2 fold change (FC)|> 1 and p  < 0.05. A clustering heatmap and volcanic distribution of the DEGs were obtained. A total of 226 differential expression genes (DEGs) were identified. Overall, 90 upregulated and 136 downregulated DEGs were identified in the control and PA3264-treated groups, respectively (Fig.  5 A). Hierarchical clustering analysis of the DEGs between the control and PA3264-treated groups was presented as a heat map, indicating significant differences in the expression patterns of the DEGs between the two groups (Fig.  5 B). The DEGs were subjected to GO enrichment analysis to characterize their functions. Results showed that these DEGs were significantly enriched in GO functions associated with extracellular regions, extracellular space, neutrophil chemotaxis, and cysteine-type endopeptidase inhibitor activity (Fig.  5 C). Moreover, KEGG pathway analysis showed that the DEGs were mainly associated with cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, ECM-receptor interaction, PI3K-AKT signaling pathway, IL-17 signaling pathway, and chemokine signaling pathway in control vs. PA3264-treated groups (Fig.  5 D). Furthermore, some DEGs related to the PI3K/AKT signaling pathway with significant fold differences in expression were verified by qRT-PCR. The results were consistent with the RNA-seq results (Fig.  5 E).

RNA-seq analysis of PA3264 in 4T1 orthotopic tumors. A The bar chart showed the number of upgraded or downgraded DEGs in tumors between the control and PA3264-treated groups. B Clustering heatmap analysis of DEGs in different groups using RNA-seq analysis. C GO enrichment analysis of the candidate targets of PA3264 in the treatment. The top 10 GO functional categories were selected. D KEGG pathway enrichment of the candidate targets of PA3264 in treating TNBC. The size of the circles represents the number of genes, and the color represents the p-value . E qRT-PCR verification of DEGs related to the PI3K/AKT signaling pathway. Data were presented as mean ± SEM, n = 9, * p  < 0.05, ** p  < 0.01, *** p  < 0.001 vs. the control group

Aberrant activation of the PI3K/AKT/NF-κB pathway is commonly observed in breast cancer, resulting in the increased proliferation and invasive potential of cancer cells. To predict the binding affinity of PA3264 for related proteins in the PI3K/AKT/NF-κB pathway, molecular docking studies were performed. PA3264 and the surrounding amino acid residues of macromolecular targets helped stabilize the complex structure, thus enhancing binding affinity. Figure  6 A, B depict the interaction of PA3264 with the binding site residues of PI3Kγ. The phenyl ring of Tyr867 interacted with PA3264 via face-to-face pi-pi stacking interaction with the phenyl ring of PA3264. Additionally, the hydroxy group of PA3264 formed 3H-bonds with residues Asp967, Lys833, and Val882. Next, the molecular docking of PA3264 with AKT1 (Fig.  6 C, D) and NF-κB p65 (Fig.  6 E, F) was carried out. Furthermore, the molecular docking results revealed that PA3264 had the highest binding affinity with the inhibitory targets of PI3K, with a docking score of −6.987, as shown in Table  2 .

PA3264 docked in the binding sites of macromolecular targets. i) PA3264 docked to the binding site of PI3K (PDB ID: 4HVB). A 3D picture depicting the binding mode. B 2D interaction diagram showing ligand-receptor interactions; ii) PA3264 docked at the binding site of AKT (PDB ID: 4EKL) C 3D binding pose, D 2D interaction diagram; iii) PA3264 docked at the binding site of NF-κB p65 (PDB ID: 1NFI) E 3D binding pose, F 2D interaction diagram

PA3264 caused cell cycle arrest and promoted apoptosis by regulating the PI3K/AKT/NF-κB signaling axis

To investigate the anticancer effects of PA3264 and verify the PI3K/AKT/NF-κB pathway-dependent mechanism, we measured the expression levels of related proteins using western blotting. As shown in Fig.  7 A–F, following intervention with different concentrations of PA3264 for 24 h on the 4T1 cells, the protein expression of p-PI3K, p-AKT, p-p65, and Cyclin D1 was reduced in a dose-dependent manner. And the expression levels of p-PI3K, p-AKT, p-p65, and Cyclin D1 proteins were significantly lower in the 20 mM and 40 mM groups than in the control group ( p  < 0.01 or 0.05). Consistent with the WB analysis, the mRNA expression levels of Bcl-2 and Cyclin D1 also gradually declined in PA3264-treated 4T1 cells compared to those in the control group ( p  < 0.01 or 0.05, Fig.  7 G, H), as expected. To further validate these results, we performed the same experiments using MDA-MB-231 cells. The expression levels of p-PI3K, p-AKT, p-p65, and Cyclin D1 proteins were significantly lower in the 10 mM and 20 mM groups than in the control group ( p  < 0.01 or 0.05, Suppl. Figure 2A-F). Moreover, PA3264 treatment significantly downregulated Bcl-2 and Cyclin D1 expression in the 10 mM and 20 mM groups compared to that in the control group ( p  < 0.01 or 0.05), as evidenced by the mRNA expression level (Suppl. Figure 2G-H). Overall, these results indicated that PA3264 suppressed the PI3K/AKT/NF-κB signaling pathway to regulate the cell cycle and apoptosis in breast cancer cells, further validating the accuracy of RNA-seq analysis and molecular docking results.

PA3264 caused cell cycle arrest and induced apoptosis in 4T1 cells via the PI3K/AKT/NF-κB signaling pathway. A – B Dose–response effects of PA3264 on signaling pathways in 4T1 cells treated with the indicated concentrations for 24 h. The levels of p-PI3K, PI3K, p-AKT, AKT, p65, p-p65, and Cyclin D1 in PA3264-treated 4T1 cells were examined using western blotting. C – E The relative intensities of all phosphorylated proteins were calculated after normalization to the total proteins. F Relative intensities of Cyclin D1 were calculated after normalization to HSP90 expression. G – H The expression of Cyclin D1 and Bcl-2 mRNA in 4T1 cells was verified by qRT-PCR. I – J 4T1 cells were treated with 20 mM PA3264, 0.1 μM LY294002, and 10 μM JSH-23 for 24 h. The expression levels of PI3K, AKT1, p65, their phosphorylated forms, and Cyclin D1 were assessed in cell lysates by western blotting analysis. K – M Relative intensities of all phosphorylated proteins were calculated after normalization to total protein. N The relative intensity of Cyclin D1 was calculated after normalization with HSP90 expression. Data were presented as the mean ± SEM (n = 3). * p  < 0.05, ** p  < 0.01, and *** p  < 0.001, compared with levels in the untreated group or the group administered alone

To further validate the mechanism of PA3264 in the treatment of TNBC, PI3K and NF-κB pathway inhibitors were used in western blotting experiments. LY294002 and JSH-23 have been reported to be PI3K and NF-κB pathway inhibitors, respectively [ 26 , 27 , 28 , 29 ]. We investigated the inhibitory effects of PA3264 in combination with LY294002 on PI3K/AKT signaling and JSH-23 on NF-κB signaling in breast cancer cells (MDA-MB-231 and 4T1). LY294002 and PA3264 reduced p-PI3K, p-AKT, and p-p65 protein expression in comparison with the control group (Fig.  7 I–M and Suppl. Figure 2I-M). Compared with the LY294002 group, the expression of p-PI3K, p-AKT and p-p65 proteins decreased with no significant difference, when PA3264 was co-administered with LY294002. Still, Cyclin D1 protein expression had a significant decreasing trend ( p  < 0.01, Fig.  7 N and Suppl. Figure 2N), which indicated that PA3264 exerted a part of its anti-TNBC effect by inhibiting the PI3K/AKT signaling pathway. In addition, JSH-23 and PA3264 inhibited the expression of p-p65 and Cyclin D1 proteins in comparison with the control group. The combination of PA3264 and JSH-23 reduced the expression of p-p65 and Cyclin D1 proteins without significant difference compared with the JSH-23 group, suggesting that PA3264 played a part of its anti-TNBC effect by suppressing the NF-κB signaling pathway. Therefore, in this study, we found that PA3264 exerted a certain anti-TNBC effect by inhibiting the PI3K/AKT/NF-κB signaling pathway.

Squama Manis has a long history of medicinal application in China to invigorate blood circulation and remove blood stasis. Clinically, Squama Manis is used to treat a wide range of diseases with significant results, not only for breast-related diseases but also for other gynecological disorders, including fibroids [ 31 ] and infertility [ 32 ]. Although the effect of Squama Manis has been demonstrated through the accumulation of real-life experiences, the role of individual biochemically active ingredients has not been extensively investigated. Further research should be conducted to develop active compounds as alternatives to Squama Manis to protect this endangered species.

Breast cancer is one of the most common breast-related diseases with a high incidence and mortality rate. TNBC, the most aggressive subtype, quickly metastasizes, and exhibits strong drug resistance. Chemotherapeutic agents are widely used to treat patients with advanced BC. However, approximately 50% of the patients rapidly develop acquired resistance [ 30 ]. Therefore, it is still important to discover new TNBC treatments, and providing more effective treatments with fewer side effects is the primary and challenging research direction. Traditional Chinese medicine (TCM) plays an anticancer role by regulating the immune system, anti-tumor angiogenesis, tumor cell apoptosis, autophagy dysfunction, and other mechanisms. An increasing body of literature reports traditional Chinese medicine and its active constituents possess significant anticancer activity, such as Icariside II [ 31 ] and curcumin [ 32 , 33 ]. Therefore, exploring new anticancer agents from TCM and their mechanisms in treating TNBC has become a research hotspot in recent years.

It is widely believed that restraining the PI3K/AKT/NF-κB pathway is a crucial target for treatment. The omnipresent PI3K/AKT pathway is involved in apoptosis, proliferation, and differentiation by regulating a wide range of target proteins, including NF-κB [ 34 ]. The phosphorylation of p65 leads to NF-κB translocation into the nucleus and binding to specific sequences in the promoter regions of target genes encoding mediators such as Cyclin D1, Bcl-2 [ 35 , 36 ]. By promoting Cyclin D1 and Bcl-2 expression, the NF-κB pathway drives cell cycle progression and promotes the proliferation of cancer cells.

Previous studies have found a peptide, PA3264, derived from Squama Manis, but its pharmacological activity in breast diseases is unknown. In this study, we found that PA3264 significantly inhibited the viability of BC cells (MDA-MB-231 and 4T1) in a dose-dependent manner. In addition, mechanistic studies have suggested that PA3264 downregulated the phosphorylation of PI3K, AKT and p65, and decreased the expression of Cyclin D1 and Bcl-2, thereby inhibiting cell proliferation and inducing apoptosis. Consistent with the results of the in vitro experiment, PA3264 significantly inhibited tumor development and induced apoptosis in vivo. Treatment with PA3264 did not substantially affect the average body weight, the liver and kidney function of mice. Taken together, these results suggest that PA3264 is a potentially safe and effective anticancer treatment for TNBC.

There are two main limitations with regard to this research. The present study yielded that PA3264 inhibited cell migration only at 4T1. However, the in vivo effects need to be further investigated. Transcriptome sequencing results enriched multiple signaling pathways that may inhibit TNBC, but we focused only on the PI3K/AKT and NF-κB pathways. The current results suggest that PA3264 inhibited the activation of the PI3K/AKT/NF-κB pathway by suppressing PI3K phosphorylation. To further support this, PI3K and NF-κB pathway inhibitors were used in western blotting experiments. Therefore, in this study, we found that PA3264 exerted a certain anti-TNBC effect by inhibiting the PI3K/AKT/NF-κB signaling pathway, but other mechanisms of action also exist. More studies are needed to address these limitations in the future to characterize its therapeutic functions and elucidate other molecular mechanisms that exert its biological effects in TNBC.

In this study, we preliminarily clarified the anti-tumorigenic activity and mechanisms of action of PA3264 in TNBC treatment. Our findings suggested that PA3264 inhibited tumor growth by modulating the PI3K/AKT/NF-κB signaling axis, suppressing proliferation and promoting apoptosis. Altogether, this study indicates that PA3264 as a potential leading compound has a therapeutic benefit against TNBC and promises to be a substitute for rare and endangered Squama Manis in the treatment of TNBC.

Availability of data and materials

Data will be made available on request.

Abbreviations

Triple-negative breast cancer

Phosphatidylinositol 3-Kinase

Protein kinase B

Nuclear factor-kappa B

Traditional Chinese medicine

Progesterone

Human epidermal growth factor receptor-2

Lactate dehydrogenase

Differential expression genes

Gene ontology

Kyoto encyclopedia of genes and genomes

Breast cancer

Mammalian target of rapamycin complex 1

Alanine aminotransferase

Aspartate aminotransferase

Blood urea nitrogen

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Acknowledgements

We are grateful to the Fifth Medical Center of the Chinese PLA General Hospital for providing an excellent testing platform.

The work involved in this article was supported by the National Natural Science Foundation of China (No. 81721002, No. 82230118) and the Consulting Project Funds of the Chinese Academy of Engineering (No. 2023-XZ-88).

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School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China

Xiaorong Hou, Yuanyuan Chen, Youping Liu & Xiaohe Xiao

Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China

Xiaorong Hou, Zhaofang Bai, Yuanyuan Chen, Wei Shi, Huijie Yang, Xiaoyan Zhan, Xu Zhao & Xiaohe Xiao

Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China

Research Institute of Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China

Ruisheng Li

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Contributions

Xiaorong Hou performed the main experiments and prepared a draft of the manuscript. Zhaofang Bai designed the research. Yuanyuan Chen, Wei Shi, and Huijie Yang assisted in revising the manuscript. Ruisheng Li assisted in vivo experimentation. Xiaoyan Zhan and Youping Liu assisted in the data preparation and analysis. Xu Zhao and Xiaohe Xiao supervised and edited the manuscript.

Corresponding authors

Correspondence to Xiaoyan Zhan , Youping Liu , Xu Zhao or Xiaohe Xiao .

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All of the experiments were performed under the approved guidelines of the animal ethics committee of the Fifth Medical Centre, Chinese PLA General Hospital (IACUC-2023–0014).

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Supplementary Information

13020_2024_979_moesm1_esm.tiff.

Supplementary material 1: Fig. 1 Effects on liver and renal function indicators in various groups of mice.  A  Alanine aminotransferase (ALT),  B  aspartate aminotransferase (AST),  C  blood urea nitrogen (BUN), and  D  creatinine (CRE) levels in the serum were measured. The figure shows the mean ± SEM of the experimental data for each group. Compared with the normal and control groups, * p < 0.05, ** p < 0.01, *** p < 0.001. Compared with the cisplatin group, # p < 0.05, ## p < 0.01, ### p < 0.001, n = 7-9.

13020_2024_979_MOESM2_ESM.tiff

Supplementary material 2: Fig. 2 Effect of PA3264 with pathway inhibitors on PI3K/AKT/NF-κB signaling in MDA-MB-231 cells.  A-B  MDA-MB-231 cells were treated with the indicated concentrations of PA3264 for 24 h, and the expression levels of PI3K, AKT1, p65, Cyclin D1, and all phosphorylated forms in total cell lysates were evaluated by western blot analysis.  C-E  The relative intensities of all phosphorylated proteins were calculated after normalization to the total proteins.  F  Relative intensities of Cyclin D1 were calculated after normalization to HSP90 expression.  G-H  Analysis of Cyclin D1 and Bcl-2 expression in MDA-MB-231 cells treated with PA3264 at different concentrationsusing qRT-PCR.  I-J  MDA-MB-231 cells were treated with 20 mM PA3264, 0.1 μM LY294002, and 10 μM JSH-23 for 24 h. The expression levels of PI3K, AKT1, p65, their corresponding phosphorylated forms, and Cyclin D1 were assessed in cell lysates using western blotting analysis.  K-M  Relative intensities of all phosphorylated proteins were calculated after normalization to total protein. N The relative intensity of Cyclin D1 was calculated after normalization with HSP90 expression. Data are presented as mean ± SEM from three independent experiments. * p < 0.05, ** p < 0.01, and *** p < 0.001, compared with levels in the untreated group or the group administered alone.

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Hou, X., Bai, Z., Chen, Y. et al. Dipeptide PA3264 derived from rare and endangered Squama Manis is a novel bioactive peptide for the treatment of triple-negative breast cancer. Chin Med 19 , 112 (2024). https://doi.org/10.1186/s13020-024-00979-x

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Received : 27 February 2024

Accepted : 04 August 2024

Published : 21 August 2024

DOI : https://doi.org/10.1186/s13020-024-00979-x

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Manuka honey reduces breast cancer cell growth by 84% in prelim studies

Manuka honey reduced breast cancer cell growth by 84% without harming healthy cells or causing major side effects, according to preliminary studies. The findings open the door to developing a natural, non-toxic supplementary, or potentially stand-alone, anticancer treatment.

Nutraceuticals – a combination of ‘nutrition’ and ‘pharmaceuticals’ that, let’s be honest, smacks of marketing speak – are products that, apart from providing nutritional value, also have health-improving properties. Ginseng, green tea , Echinacea, and omega-3 are common examples. So is Manuka honey, produced from the nectar collected by honey bees when they pollinate the mānuka, a species of tea tree indigenous to New Zealand and southeast Australia.

Manuka honey has been demonstrated to have antibacterial , antioxidant and healing properties that are thought to be due to its specific composition, which differs from other kinds of honey . Now, preliminary studies by researchers at UCLA have found that this nutraceutical might aid in breast cancer prevention and treatment.

“The findings provide hope for [the] development of a natural, less toxic alternative to traditional chemotherapy,” said Dr Diana Márquez-Garbán, associate professor of medicine at the UCLA David Geffen School of Medicine, and the study’s lead author. “Although more research is necessary to fully understand the benefits of natural compounds in cancer therapy, this study establishes a strong foundation for further exploration in this area.”

In those diagnosed with estrogen receptor (ER) positive breast cancer – which is about 60% to 70% of people diagnosed with breast cancer – the cancer cells have receptors that allow them to use the hormone estrogen to grow. While treatment with anti-estrogen, or endocrine, therapy can block tumor growth in most patients, some become resistant to the treatment, often leaving potentially toxic chemotherapy as the only alternative.

The researchers first grew ER-positive and triple-negative breast cancer cells, another of the most common types of breast cancer, in the lab. In the ER-positive cells treated with Manuka honey or dehydrated Manuka honey powder, they observed a significant dose-dependent inhibition of cancer cell proliferation compared to those treated with controls. For the triple-negative cells, the antitumor effect was more modest. When Manuka honey was combined with tamoxifen, a drug widely used as an anti-estrogen therapy, ER-positive cell proliferation was markedly suppressed and significantly less than that of either treatment administered alone.

Examining the cells more closely, the researchers found that the honey caused a reduction in blood estrogen levels and estrogen receptors in the tumors and further disrupted cancer progression by inducing apoptosis, or cell death, in the tumor cells.

They then moved on to testing Manuka honey in animal models. Mice that had been implanted with human ER-positive breast cancer cells and developed a tumor were given Manuka honey orally. The honey-treated mice showed significantly suppressed tumor growth compared to controls. Overall, it inhibited the growth and progression of an established human breast cancer tumor by 84% without affecting healthy cells.

“These findings indicate that natural compounds such as Manuka honey, with significant antitumor activity and selectivity towards hormone receptor-positive breast cancers, may be further developed as a supplement or potential alternative to cytotoxic anticancer drugs that have more non-selective adverse effects,” the researchers concluded.

The study was published in the journal Nutrients .

Source: UCLA Health

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