Breast Cancer Clinical Trials Research Articles

Abstract PO2-10-06: The Rising Burden of Contraception Requirements in Breast Cancer Clinical Trials: Time for Change?

Abstract Background: Breast cancer clinical trials often involve therapies with potentially deleterious effects on the fetus and the baby in the event of pregnancy or breastfeeding. Consequently, eligibility criteria include contraceptive requirements for both the patient and their partner. Patient feedback on the burden of requirements in clinical trials prompted an evaluation of changes in contraceptive requirements in breast cancer clinical trials over the past two decades. Methods: Breast cancer ClinicalTrials.gov trials protocols over three periods of enrollment were reviewed: 01/01/2001 - 01/01/2002, 01/01/2011 - 01/01/2012, and 01/01/2021 - 01/01/2022. Inclusion criteria: 1. Interventional studies including (neo)adjuvant or palliative systemic therapy, 2. Premenopausal female patients. Data, including the required number, types, and duration of contraceptive strategies, treatment regimen, and study design, were collated. A descriptive analysis by time period was performed. Results: 305 studies were included from the three periods: 63 (2001), 127 (2011), and 115 (2021). Of these, contraception requirements were specified in ClinicalTrial.gov protocol information in 4, 61, and 71 CT for 2001, 2011, and 2021, respectively, limiting our analyses in the two later periods. Complete data is available in Table 1. Conclusions: Our data demonstrates a time trend towards more stringent contraception requirements in breast cancer clinical trials inclusion criteria. The impact of contraception burden on enrollment, patient compliance, and investigator insight warrants further assessment. Citation Format: Camila Chiodi, Munzir Hamid, Catherine Weadick, Maeve Hennessy, Ana Martin-Quesada, Louise Kenny, Matteo Lambertini, Ines Vaz Luis, Seamus O'Reilly. The Rising Burden of Contraception Requirements in Breast Cancer Clinical Trials: Time for Change? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-10-06.

Abstract PO3-10-10: Are we adequately integrating patient reported outcomes in breast cancer clinical trials?

Abstract Background: Integrating patient reported outcomes (PROs) in cancer care enhances clinical outcomes and creates a paradigm shift in providing patient-centered care. Several studies performed in the past 15 years have demonstrated that systematic monitoring of patients using PROs through surveys improve patient-clinician communication, clinician awareness of symptoms, symptom management, patient satisfaction, quality of life, and overall survival. There has been uncertainty over the type of PRO system to implement in cancer care, how to evaluate PRO in clinical trials, and how to compare this to the clinician common terminology criteria for adverse events (CTCAE). The PRO concept was first introduced in 1975 with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) survey. In May 2018, the National Cancer Institute established the PRO-CTCAE to be utilized for cancer patients to report and grade their treatment related adverse events, like that of clinician reported CTCAE. The goal of our study was to evaluate frequency of PRO incorporation in phase III breast cancer clinical trials. Methods: New England Journal of Medicine, Journal of Clinical Oncology, and Lancet were systematically searched to identify phase III breast cancer clinical trials published between January 2018 and June 2023. A total of 113 phase III studies were identified, 87 of which had reported protocols. Studies that did not demonstrate protocols on these search engines were not included in the review. Of these 87 clinical trials, 36 studies documented evaluation of PRO. These studies were segregated by year of publication. For each year, the number of total phase III breast cancer clinical trials that were published were compared to those that were published and evaluated PRO. A percentage was generated and allowed for a longitudinal trend to be analyzed over a 5-year period to assess if there was improved frequency of PRO integration into breast cancer clinical trials. Summary statistics were calculated using SAS 9.4. Results: 36 of 113 trials demonstrated PRO use and 26 utilized EORTC-QoL, 1 used PRO-CTCAE, and 9 used another measure of PRO assessment within their study protocol (such as FACT-B and PHQ-9. Additionally, in 2018, 33% of published breast cancer studies included PRO data. Since then, there have been fluctuations in breast cancer studies collecting PRO; 2019: 33%, 2020: 47%, 2021: 43%, 2022: 73%, and since the start of 2023: 9%. Conclusions: Our data suggests a trend towards improvement in frequency of PRO data collection in breast cancer clinical trials over the past 5 years, exemplified by the marked increase in 2022. There remains a need to incorporate PROs in clinical trials and routine care to improve patient experience and provide patient-centered care. Citation Format: Yadav Rina, Zhengyan Huang, Jessica Moss, Garima Gupta. Are we adequately integrating patient reported outcomes in breast cancer clinical trials? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-10-10.

Abstract PO5-10-06: A Pilot Study for Clinical Research Nurse Navigation at an Urban NCI-Designated Comprehensive Cancer Center

Abstract Background: Breast cancer is now the leading cause of cancer death for non-Hispanic Black women in Georgia with non-Hispanic Black women 40% more likely to die of breast cancer compared to White women. Inadequate representation of patients in clinical trials may contribute to health care inequity, though prior work has also shown disparate outcomes on similar clinical trials at Emory, suggesting differences in tumor biology may also be contributing to the disparity. Improving diversity in trial participation is imperative to better understand these differences, particularly with newer molecularly targeted therapies. We aimed to utilize Clinical Trials Nurse Navigation to increase clinical trial enrollment at an urban NCI-designated comprehensive care center in Atlanta, Georgia. Methods: A prospective pilot study was conducted investigating the role of a Clinical Research Nurse as a dedicated Clinical Trials Nurse Navigator to identify, pre-screen, and refer potential patients to both breast and next generation sequencing (NGS)-driven basket clinical trials at the Winship Cancer Institute at Emory University. The role also included centralizing all molecular data from patients with stage IV breast cancer into a database as a tool to refer patients to NGS-driven clinical trials. This role expands upon the Institute’s current research nursing scope to better meet the needs of our diverse patient population. Our catchment area is 35% non-Hispanic Black or African American. The nurse prescreened patients with stage IV breast cancer from breast oncology clinic templates and the breast NGS database to match them with clinical trials, with a particular emphasis on patients with stage IV triple negative breast cancer. The study began in January 2022 and is currently ongoing. Results: Since study initiation in January 2022, there has been a 27% increase in breast cancer clinical trial enrollment over a 12-month period. Over the last 6 months from January 2023, this has increased even further with 57 patients enrolled onto breast cancer clinical trials compared to a total enrollment of 70 patients onto breast cancer clinical trials in 2022 (Table 1). Of these patients, 11% enrolled in NGS-driven clinical trials in 2022 to present compared to 0% in 2021. Twenty-two (31.4%) non-Hispanic Black women enrolled onto breast cancer clinical trials in 2022 with another 21 (36.8%) non-Hispanic Black women enrolled thus far in 2023 (Table 1). Conclusion: Disparities in clinical trial enrollment may contribute to racial inequities in breast cancer outcomes. Implementation of clinical research nurse navigation has successfully improved clinical trial enrollment and diversity in clinical trial enrollment at our urban cancer center. Through increasing clinical trial prescreening, centralizing an NGS database, and dedicated nurse support to allow patients to navigate onto clinical trials, we achieved a 21% improvement in clinical trial enrollment from 2021 to 2022 and are on track to increase enrollment by 200% by the end of 2023. Clinical trials nurse navigators serve as an essential link between clinical trial patients and their providers, and should strongly be considered a key component of all clinical trials programs. Table 1 Breast Working Group Patient Enrollment by Race and Ethnicity, 2019-2023 Citation Format: Lizzie Huckaby, Maisey Ratcliffe, Madison Canning, Demetria Smith-Graziani, Kevin Kalinsky, Manali Bhave. A Pilot Study for Clinical Research Nurse Navigation at an Urban NCI-Designated Comprehensive Cancer Center [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-10-06.

Abstract PO1-10-12: Advancing Gender Equity: A Closer Look at Women's Representation in Leading Breast Cancer Clinical Trials

Abstract Introduction: Clinical trials serve as pivotal sources for evidence-based medicine, wielding substantial influence within the medical and scientific community. In recent years, heightened attention has been directed towards encouraging greater female involvement and advancing their representation across various domains of the medical field. Female oncologists tend to focus more over breast cancer as a subspeciality and focused practice. Consequently, this observational study seeks to assess the present status of gender equity in leading breast cancer clinical trials, with the aim of identifying potential concerns and mitigating future risks of bias. By delving into this analysis, we can shed light on the current landscape and pave the way for improved inclusivity and fairness in breast cancer research. Methodology: To examine the portrayal of female principal investigators (PIs) in breast cancer clinical trials over the past two decades, we conducted a thorough search of breast cancer clinical trials listed on ClinicalTrials.gov. Furthermore, we employed https://gender-api.com to assess the gender of each PI and calculate the experience in the medical field of the PI by subtracting the PI graduation year from the year of conducting the clinical trial. In addition, we gathered pertinent details concerning the PIs and the clinical trials, and subsequently subjected the data to univariate analyses to detect any noteworthy distinctions between male and female PIs. Results: Over the span of the past twenty years, a total of 9,145 cancer clinical trials were conducted, with 1,127 (12.32%) focusing specifically on breast cancer. Through our rigorous efforts, we managed to gather comprehensive information about the principal investigators (PIs) in 788 (69.92%) of these clinical trials. Notably, we discovered that 419 (53.17%) of these trials were led by female investigators. Upon scrutinizing the characteristics of the PIs, we observed several significant distinctions between male and female PIs. Female PIs exhibited a lower median age (57.0 vs. 60.0) and possessed less medical experience (17 vs. 22 years) compared to their male counterparts (P< 0.001). Furthermore, we found a substantial divergence in the funding sources for the clinical trials between the genders. Female-led trials received a lower percentage of industrial funding (13.1% vs. 24.2% for males, P< 0.001) but showcased a significantly higher percentage of university funding (38.7% vs. 28.0% for males, P< 0.001). Most of the clinical trials led by female PIs were categorized as phase 2 trials (82.8% vs. 66.8% for males) and were conducted in single centers (61.2% vs. 52.6% for males), demonstrating a noteworthy statistical difference (P< 0.001) in both cases. However, no statistically significant disparities were found between male and female PIs in terms of termination rates, publication rates, or the type of intervention utilized in the clinical trials. Furthermore, the ratio of females PI wasn’t different throughout the time as the liner regression model estimated effect was -0.009 with P= 0.065. Conclusions: The study shows the great effort done by female researchers, even though they have lower age, experience, and support from the industrial companies and lower opportunity to have bigger multicenter clinical trials, they still manage to have equivalent rate of termination and publication of the clinical trials showing their capability to lead clinical trials and the need to be supported to maintain the gender equity in leading the breast cancer clinical trials. However, female involvement in other cancer sites might be different and needs to be looked at. Citation Format: Abdulrahman Alhajahjeh, Ghayda’ Bader, Basil Abdin, Taima’ Bader, Saji Aweidah, Layla El-Amayreh, Hikmat Abdel-Razeq. Advancing Gender Equity: A Closer Look at Women's Representation in Leading Breast Cancer Clinical Trials [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-10-12.

Abstract PO3-09-07: When We Tri(al): Reaching, Motivating, & Effectively Engaging Black Women In Breast Cancer Clinical Trial Research

Abstract According to the American Cancer Society, Black women in the United States are 41% more likely to die from breast cancer than non-Hispanic white women. A systematic review of participation in clinical trials found that Black patients comprised less than 4% of all patients enrolled in clinical trials for emerging immune-based cancer treatments. The physiology of Black women has not been a significant consideration in clinical trial research. Clinical trial education, recruiting, and participation are not commensurate with the burden of disease. TOUCH, The Black Breast Cancer Alliance (TOUCHBBCA) launched the When We Tri(al) Movement (WWT) in January 2022 with robust multi-media support and nationwide community event activations to educate and empower Black women with culturally-agile messaging from the trusted voices of Black Breast Cancer survivor/thrivers. WWT provides an innovative and engaging learning platform that clearly depicts how clinical trials work, explains standard of care, dispels historical myths, establishes trust, and empowers self-advocacy. To date, whenwetrial.org has garnered over 108,000 visits and sent nearly 11,000 Black women to clinical trial portals. One-third of unique website visitors have gone into clinical trial search portals. Over a sixteen day period in late June and early July of 2023, TOUCHBBCA conducted research among Black women who joined the When We Tri(al) movement using a pre-experimental, retrospective pre-then-post test (RPTP) survey design to assess growth in knowledge and behavior change among Black women exposed to the Movement. This survey received 113 respondents who self-identified as Black and assigned female at birth. Following exposure to WWT, 34.5% of respondents reported an increase in their understanding of how breast cancer clinical trials work, 31.9% reported an increase in their understanding of standard of care in breast cancer clinical trials, and 40.7% reported an increased understanding of why clinical trials are important for Black women. 32.7% of survey respondents were more likely to consider participating in a clinical trial after interacting with the WWT movement. After interacting with the movement, 31% of respondents took active steps to participate in a clinical trial—specified as searching for clinical trials in a portal, asking about clinical trial options, talking to a doctor about clinical trials, etc. Another 17.7% of respondents reported supporting a loved one in taking steps to participate in a clinical trial only after interacting with WWT. The majority of respondents reported first hearing about WWT through social media (59.2%), followed by “Other” (the majority of write-in responses named Google or a friend) (19.5%). Respondents reported that the most convincing WWT messages were delivered via social media (26.6%) and in-person conversations (20.4%). Not only is When We Tri(al) educating and equipping Black women with critical clinical trial knowledge, but the movement is driving significant behavior change by Black women around clinical trial participation. Citation Format: Ricki Fairley, Emily Powers, Hayley Brown. When We Tri(al): Reaching, Motivating, & Effectively Engaging Black Women In Breast Cancer Clinical Trial Research [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-07.

Abstract PO5-17-04: Tolerability of pertuzumab in older adults with HER2 positive breast cancer: A single institution experience

Abstract Background: Tumor HER2 over-expression occurs in 10 to 15% of older adults with breast cancer (BC). Combination HER2-directed therapy (pertuzumab and trastuzumab) with chemotherapy (CT) is the standard treatment for early and advanced HER2-positive bc. However, a study of more than 1,300 Medicare beneficiaries showed that about half of patients (pts) aged 65 or older with stage I to III HER2 positive bc did not receive trastuzumab-based therapy. This is likely due to concern for tolerability as older women remain underrepresented in clinical trials of breast cancer making it difficult to extrapolate tolerability of these agents in these patients. In the Neosphere and TRYPHAENA studies, the mean age of pts were 49.8 and 50.6 years, respectively. We examined the real-world tolerability of pertuzumab in combination with trastuzumab and systemic ct in women over the age of 65 with HER2 positive bc. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts over the age of 65 with early or advanced HER2 positive bc treated at The Ohio State University Comprehensive Cancer center from January 1, 2015 to May,1 2020. Descriptive statistics (means, standard deviations, medians and ranges for continuous variables and frequencies and percents for categorical variables) were used to summarize disease and patient characteristics for pts enrolled in this study and treated with pertuzumab. The total number of planned and completed cycles of treatment as well as the number of treatment delays and dose reductions were also summarized using frequencies and percentages. The same descriptive statistics were used to summarize the number of grade II or IV toxicities and pathologic complete response (pCR) in the neoadjuvant setting. Results: A total of 71 pts met inclusion criteria. Mean age was 76 years (SD 4.1). Of these pts, 62 had stage I-III disease and 9 had metastatic disease. Additionally, 68% (48/71) had estrogen positive (ER) disease whereas 32% (23/71) had ER negative disease. Neoadjuvant systemic therapy was provided to 81% (50/62) of non-metastatic pts and 19% (12/62) received adjuvant therapy. The median number of completed neoadjuvant cycles (ct plus trastuzumab and pertuzumab) was 5.4 (SD 1.5). Among those who received pertuzumab with systemic ct in the neoadjuvant setting, 46% (23/50) of pts achieved a pCR (56% for ER negative disease and 41% for ER positive disease) The median number of completed adjuvant cycles (ct plus trastuzumab and pertuzumab) was 4.9 (SD 2.0). Pts with stage I to III disease completed a mean of 8.6 (SD 5.0) targeted therapy cycles (pertuzumab/trastuzumab). Pts with metastatic disease had a median of 5.7 (SD 1.0) cycles of ct plus trastuzumab and pertuzumab and received a mean of 34.4 (SD 36.0) cycles of maintenance pertuzumab. Treatment delay by 7 or more days occurred in 11% (8/71) of pts whereas 25% (18/71) of pts discontinued pertuzumab early. Pertuzumab termination occurred due to toxicity in 44% (8/18), metastasis in 11% (2/18), and other causes in 44% (8/18) of cases. For toxicities, 2% (1/51) of patients reported grade 3 pain, 25% (2/8) reported grade 3 fatigue, and 12% reported grade 4 diarrhea (1/8) (Table 1). Conclusions: Our study showed that pertuzumab was well tolerated in older pts with bc in the real-world setting. However, 25 % of pts still discontinued pertuzumab early which illustrates the importance of identifying pts who are at higher risk for toxicities prior to starting treatment. Table 1 Reported adverse events in patients age 65 and older receiving pertuzumab Citation Format: Nicole Williams, Austin Warmbier, Dureti Doto, Marilly Palettas, Julie Stephens, Dionisia Quiroga, Kai Johnson, Ashley Pariser, Mathew Cherian, Sagar Sardesai, Daniel Stover, Margaret Gatti-Mays, Robert Wesolowski, Bhuvana Ramaswamy. Tolerability of pertuzumab in older adults with HER2 positive breast cancer: A single institution experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-17-04.

Abstract PO1-10-11: Illuminating Breast Cancer Clinical Trials: Unpublication Rates, Causes , and Recommendations

Abstract Introduction: Breast cancer stands as the most prevalent cancer among women worldwide. Recent years have witnessed remarkable improvements in patient’s outcome, primarily attributed to advancements in management strategies. However, the introduction of novel management approaches necessitates rigorous evaluation through clinical trials, ensuring both their safety and effectiveness. Conducting these trials entails significant financial investments and time commitments, making them susceptible to termination for various reasons. This study aims to investigate the factors that contribute to an increased likelihood of breast cancer clinical trial termination. Methodology: A thorough and extensive exploration of ClinicalTrials.gov was undertaken in order to discover completed clinical trials focused on treating breast cancer from 2000 to 2020. By employing the distinctive National Clinical Trial number (NCT) identifier, trial's status; whether completed or terminated, was determined. Subsequently, a meticulous evaluation was carried out on these trials to ascertain the factors that contributed to their termination. In order to unveil the noteworthy factors linked to publication, a comprehensive analysis encompassing both univariate and multivariate approaches was conducted. Results: During the specified period, a noteworthy number of oncology clinical trials, totaling 9,145, were conducted. Among them, 12.3% (n=1,127) were focused on breast cancer. These breast cancer trials managed to recruit an impressive 2,669,749 patients. However, it is concerning to note that a significant portion, 38.1% (n=429), of the breast cancer trials did not result in published findings, despite enrolling a considerable number of patients (n= 2,397,179). Our comprehensive univariate analysis revealed several significant associations between the characteristics of clinical trials and their likelihood of going unpublished (P< 0.001). Factors such as funding, phase, masking, center type (single vs multi), and country of conduct were all found to have a statistically significant impact on the publication status. Furthermore, our meticulous multivariate analysis demonstrated that certain criteria were associated with higher odds of publication. These included trials that recruited >50 patients, multicenter trials, studies implemented masking, phase-3 trials and those that included low- and middle-income countries (LMIC), Table. Conclusion: Our findings indicate that the unpublication rate of clinical trials was alarmingly high. We identified that the sample size, masking, multicenter involvement and phase of the trial impact significantly on publication rate . This knowledge can be valuable for researchers, funding agencies, and other stakeholders who can prioritize resource allocations and improve patients care. Table: Multivariate analysis, factors that impact publication rate Citation Format: Abdulrahman Alhajahjeh, Ghayda’ Bader, Saji Aweidah, Taima’ Bader, Basil Abdin, Layla El-Amayreh, Hikmat Abdel-Razeq. Illuminating Breast Cancer Clinical Trials: Unpublication Rates, Causes , and Recommendations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-10-11.

Abstract PO3-13-05: PD-L1 and PD-L2 Protein Expression is Frequently Discordant in Breast Cancer

Abstract Background: In neoadjuvant setting, PD-1 inhibitors have shown significantly higher pathological responses in patients (pts) with early-stage triple-negative breast cancer (TNBC) irrespective of PD-L1 status. However, durable responses are less common in estrogen receptor-positive (ER+) pts. Most breast cancer (BC) clinical trials of PD-1 inhibitors have thus far focused on PD-L1 expression for patient eligibility. The alternative PD-1 ligand, PD-L2, with reported ~4-fold greater affinity for PD-1, has been largely understudied. We recently reported that high cancer cell protein levels of PD-L2 in pts with treatment-naïve ER+ BC was an independent predictor of shorter progression-free survival. PD-L2 expression was significantly high in ER- group as well, however, given the low numbers of ER- pts, the study was not powered enough to determine the correlation of PD-L2 with PFS in the ER- subgroup. These findings suggest that PD-L2 has an important role in BC and combined PD-L1/PD-L2 status may help improve BC pt selection for PD-1 inhibitors. We therefore initiated efforts to determine baseline expression patterns of PD-L1 and PD-L2 in BC. Methods: PD-L1 and PD-L2 protein levels in cancer cells and tumor-infiltrating immune cells were prospectively analyzed by immunohistochemistry (IHC) using validated antibodies in diagnostic core biopsies of 31 consecutive pts diagnosed with localized or locoregional ER+/HER2- BC or TNBC. Percent positivity of PD-L1 and PD-L2 in cancer cells and immune cells was determined by our breast pathologist. Detectable PD-L1 or PD-L2 expression in ≥1% of cancer cells or stromal immune cells was considered positive. Spearman correlation and Wilcoxon paired analyses were used to measure and correlate PD-L1 and PD-L2 protein expression in cancer and immune cells. Results: There was no significant correlation between PD-L1 and PD-L2 expression, neither across all cases (N=31), nor within ER+ (N=22) or TNBC (N=9) cases. However, PD-L1 and PD-L2 expression patterns in BC differed in several ways. PD-L1-positivity in immune cells was higher than in cancer cells (median=5.0% vs. 0.0%; p=0.001), whereas PD-L2-positivity was higher in cancer cells than in immune cells (median=30% vs. 5.0%; p< 0.001). PD-L1 positivity in cancer cells and immune cells were positively correlated in TNBC (rho=0.69, p=0.04) but not in ER+ BC. Conversely, PD-L2 positivity in cancer cells and immune cells were positively correlated in ER+ BC (rho=0.68, p=0.001) but not in TNBC. TNBC diverged from ER+ BC by displaying higher PD-L1 positivity in immune cells (median=20.0% vs. 1.0%; p=0.004). By the conventional cut point for positivity of ≥1% for PD-L1 and PD-L2 in cancer cells or immune cells, all TNBC tumors were PD-L1-positive (9/9), with 8 also being PD-L2-positive. Of the 22 ER+ cases, 16 were PD-L2-positive, of which only 9 were also PD-L1-positive. Table 1. shows cross tabulation data for PD-L1 and PD-L2 status by BC subtype. Conclusions: PD-L1 and PD-L2 proteins show divergent expression and are not correlated in BC. Discordant PD-L2 and PD-L1 expression may be more common in ER+ BC than in TNBC. This finding justifies efforts to explore PD-L2 as a complementary marker to PD-L1 for improved prediction of response to PD-1 inhibitors, which may benefit patients with aggressive ER+ BC that are eligible for chemotherapy. Table 1. PD-L1 vs. PD-L2 Status by Breast Cancer Subtype Citation Format: Lubna Chaudhary, Julie Jorns, Yunguang Sun, Sailaja Kamaraju, Yee Chung Cheng, Amanda Kong, Tina Yen, Caitlin Patten, Chandler Cortina, Inna Chervoneva, Christopher Chitambar, Hallgeir Rui. PD-L1 and PD-L2 Protein Expression is Frequently Discordant in Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-13-05.

Abstract PO2-11-03: A long-term follow-up of patients who interrupted endocrine therapy to become pregnant following breast cancer surgery

Abstract Introduction: Regarding discontinue adjuvant endocrine therapy to attempt pregnancy, Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer (POSITIVE) clinical trials have revealed temporary interruption of endocrine therapy to attempt pregnancy did not confer short-term risk of breast cancer events. However, that report involved a short observation period, longer-term follow-up is required. This study was aimed to evaluate the safety of endocrine therapy interruption with long-term followed-up data base. Methods: This was a retrospective study using surveying of medical chart data between June 2007 and November 2015 at St. Luke’s International Hospital. The subjects were 65 patients with estrogen-receptor positive primary breast cancer (clinical stage I-III) who had been performed fertility preservation prior to starting breast cancer treatment. Adjuvant endocrine therapy completion was defined as 120 months (10 years) and discontinuation was defined as < 120 months. Using the definition, we classified the patients into an endocrine therapy interruption-group and a continuation-group. The primary outcome was the breast cancer free interval (BCFI). We defined breast cancer events as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer during follow-up. Results: Median follow-up period was 110 (range, 36–181) months. The number of adjuvant endocrine therapy interruption-group was 30 and continuation-group was 35. Among 65 patient, the mean patient age in the interruption vs. continuation groups were as follows: 38(range, 26-48) years vs. 36.5 (range, 26–45) years at breast cancer diagnosis and HER2 positive breast cancer was identified in 4 (11.4%) vs 4 (13.3%) patients. Clinical stages were Stage I, 9 (30%) vs. 11 (31.4%) patients; Stage II, 18 (60%) vs. 18 (51.4%) patients; and Stage III, 3 (10%) vs. 6 (17.1%) patients. Chemotherapy was administered in 17 (56.7%) and 23 (65.7%) patients, respectively. The median duration of endocrine therapy before interruption was 25.5 months: 3 (10%) patients received endocrine therapy for 0–18 months, 16 (53.3%) for 18–30 months, and 11 (36.7%) for >30 months. The BCFI was 124 and 119 months in the interruption and continuation groups, respectively (p = 0.16). There were 6 (20%) and 9 (25.7%) breast cancer events in the interruption-group and continuation-group, respectively (p = 0.4). All the pregnancies were in the endocrine therapy interruption group (17 pregnancies, 16 deliveries), with one pregnancy involving the delivery of twins. Three pregnancies were spontaneous. Endocrine therapy was resumed in 16 (59.3%) patients in the interruption-group (median time to resumption, 20.5 months). One patient developed distant metastasis during endocrine therapy interruption period. Conclusion: Among patients who performed fertility preservation prior to starting breast cancer treatment, our long-term follow-up data, almost 9 years, suggested that the BCFI was not statistically different between endocrine therapy interruption-group and continuation-group. A limitation of this study is that only three cases of Stage III breast cancer were included in the interruption group. Therefore, we consider that careful decisions should be made regarding interruption of endocrine therapy. Citation Format: Risa Kasahara, Atsuko Kitano, Fumi Akitani, Kyoko Shiota, Kumiko Kida, Junko Takei, Atsushi Yoshida. A long-term follow-up of patients who interrupted endocrine therapy to become pregnant following breast cancer surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-03.

Abstract PO3-27-08: Geographic Distribution and Accessibility of Clinical Trials for Advanced-Stage Breast Cancer in the United States: A Focus on Rural and Minority Health Disparities

Abstract Background: Our research examines the geographical distribution and accessibility of clinical trials for metastatic breast cancer patients in the U.S., spotlighting the challenges faced by rural communities and minority groups. Prior research indicated nearly half of these patients would have to commute over an hour to reach a trial site. [1] Our study provides a refreshed perspective on this issue, offering a more comprehensive analysis. Methods: Utilizing the ClinicalTrials.gov portal, we identified active interventional clinical trials for metastatic breast cancer patients as of November 25, 2022. We obtained distinct zip codes linked to these trials and, using 2020 census data, estimated the proportion of the U.S. populace residing within specific distances from these sites. Our analysis encompassed ethnicity, and other socio-economic parameters. Using GIS software, we also developed illustrative maps to visually represent the U.S. clinical trial accessibility landscape. Results: The majority of Americans diagnosed with metastatic breast cancer have clinical trials within their reach. A significant 81.8% of the U.S. populace resides within a 30-mile radius of a relevant clinical trial site. However, there is significant variation among ethnic groups, especially among American Indians, where 56.5% live within 30 miles of a clinical trial site. Conclusions: While a commendable 81.8% of the U.S. population resides within 30 miles of a metastatic breast cancer clinical trial site, our data underscores the uneven geographical spread of these trials. Our findings underscore the need for strategic initiatives to ensure clinical trials are within reach for every individual, irrespective of their location or background. Reference: 1. Galsky MD, Stensland KD, McBride RB, Latif A, Moshier E, Oh WK, Wisnivesky J. Geographic accessibility to clinical trials for advanced cancer in the United States. JAMA Intern Med. 2015 Feb;175(2):293-5. PMID: 25437434. Map of 30-, 60-, and 120-mile buffers from clinical trial sites open to patients with metastatic breast cancer. The U.S. Population living withing 30-, 60-, and 120-miles of an open clinical trial site for patients with metastatic breast cancer. Citation Format: Emily Westergard, Abigail Swenson, Zachary Schroeder, Wade Swenson. Geographic Distribution and Accessibility of Clinical Trials for Advanced-Stage Breast Cancer in the United States: A Focus on Rural and Minority Health Disparities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-08.

The role of artificial intelligence in optimising patient recruitment for breast cancer clinical trials

The role of artificial intelligence in optimising patient recruitment for breast cancer clinical trials

Racial and Ethnic Disparities in European Breast Cancer Clinical Trials

Breast cancer is the most prevalent female cancer worldwide with known correlations between the race and tumor characteristics of the patients and prognosis. International and US-based studies, however, have reported a disproportionate representation of Black and Hispanic patients in clinical trials. This is the first study assessing race and ethnicity reporting trends and inclusion in European breast cancer trials. The PubMed and ClinicalTrials.gov databases were systematically searched for trials on breast cancer treatment conducted exclusively in Europe between 2010 and 2022. Of the 97 identified trials, race was reported in 10.31%. Multinational participation, but not the study size or trial phase, was significantly associated with higher race reporting trends. These 10 trials featured a White-predominant population, with 1.08% Asian and 0.88% Black patients included. The acquisition of the race and ethnicity data of patients in European trials is lower compared to the U.S. or worldwide studies and does not permit extensive analysis of minority participation. In a limited analysis, the low rates of minority participation are concerning, based on population-based data on minorities in select European countries. These observations should encourage race reporting practices in European breast cancer trials and adequate minority participation to support the generalizability of the results of the studies and promote healthcare equity.

A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response.

We present an integrated single-cell RNA sequencing atlas of the primary breast tumor microenvironment (TME) containing 236,363 cells from 119 biopsy samples across eight datasets. In this study, we leverage this resource for multiple analyses of immune and cancer epithelial cell heterogeneity. We define natural killer (NK) cell heterogeneity through six subsets in the breast TME. Because NK cell heterogeneity correlates with epithelial cell heterogeneity, we characterize epithelial cells at the level of single-gene expression, molecular subtype, and 10 categories reflecting intratumoral transcriptional heterogeneity. We develop InteractPrint, which considers how cancer epithelial cell heterogeneity influences cancer-immune interactions. We use Tcell InteractPrint to predict response to immune checkpoint inhibition (ICI) in two breast cancer clinical trials testing neoadjuvant anti-PD-1 therapy. Tcell InteractPrint was predictive of response in both trials versus PD-L1 (AUC= 0.82, 0.83 vs. 0.50, 0.72). This resource enables additional high-resolution investigations of the breast TME.

Abstract 2569: VEGFA gene expression is associated with cell proliferation, less immune cell infiltration, and worse survival, but better response to chemotherapy and immunotherapy

Abstract Introduction: Vascular endothelial growth factor-A (VEGFA) is a well-known factor that induces angiogenesis, one of the hallmarks of cancer, which generates new blood vessels in the tumor microenvironment (TME) and provides conduit for cancer to metastasize. Interestingly, an anti-VEGFA drug (Avastin) failed to show benefit in clinical trials for breast cancer (BC). In this study we investigated the clinical relevance of VEGFA gene expression in BC. Methods: A total of 7336 BC patients from eight independent cohorts, TCGA (n= 1073), METABRIC (n= 1903), SCAN-B (GSE96058, n= 3069), GSE20194 (n=278), GSE34138 (n=178), GSE163882 (n=222), GSE25066 (n=508), and ISPY2 (GSE173839, n= 105) were analyzed. These cohorts were divided into high and low VEGFA gene expression groups using the median. Results: High VEGFA expression in BC was associated with worse overall survival in SCAN-B cohort which was validated in METABRIC cohort with overall, disease-specific, and disease-free survival (all p<0.02). VEGFA expression was higher in Triple Negative BC (TNBC) but was lower in BC with lymph node metastasis. High VEGFA BC was associated with significantly high intratumoral heterogeneity, homologous recombination defect, silent and non-silent mutations, and SNV neoantigens in TCGA, and was also associated with higher cell proliferation, evidenced by higher Nottingham histological grade, higher Ki67 gene expression, and enrichment of all the Hallmark cell proliferation-related gene sets: Mitotic spindle, G2M Checkpoint, E2F Targets, MYC Targets v1 and v2, and mTorC1 signaling, consistently, in SCAN-B, METABRIC, and TCGA cohorts. Reflecting its enhanced growth, high VEGFA expression was associated with less infiltration of fibroblasts and adipocytes (all p<0.05). Surprisingly, VEGFA expression did not enrich angiogenesis gene set in any of the cohorts, nor was related with infiltrations of blood or lymphatic vascular endothelial cells, besides pericytes. But high VEGFA BC was associated with significantly less infiltrations of anti-cancer immune cells; CD8, CD4, and dendritic cells were all significantly less, and T helper type 1 cells and regulatory T cells were significantly higher consistently in SCAN-B, METABRIC, and TCGA cohorts. VEGFA expression was significantly higher in BC that achieved pathological complete response after Anthracycline and Taxane based neoadjuvant therapy in both ER+/HER2- and TNBC subtypes in the GSE25066 cohort, and after immunotherapy in ER+/HER2- subtype, but not TNBC, in the ISPY2 clinical trial cohort. This was not validated in GSE20194, GSE34138, GSE163882 cohorts. Conclusion: Our research indicates that high VEGFA BC is associated with high cell proliferation, less immune cell infiltration, and worse survival, but better response to Anthracycline and Taxane based chemotherapy, and immunotherapy. Citation Format: Pia Sharma, Kohei Chida, Kenichi Hakamada, Kazuaki Takabe. VEGFA gene expression is associated with cell proliferation, less immune cell infiltration, and worse survival, but better response to chemotherapy and immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2569.

Abstract 2998: Regulation of epidermal growth factor receptor signaling by BRCA1-microRNA 146a network

Abstract Inherited defects in the breast cancer susceptibility gene, BRCA1 are associated with an increased risk for hereditary breast, ovarian, and other cancers. BRCA1-associated basal like breast cancers (BLBCs) are high-grade ductal carcinomas that do not express ER, PR or HER2, but frequently overexpress epidermal growth factor receptor (EGFR/ErbB1/HER1). The EGFR-driven signaling network plays a pivotal role in BLBC pathogenesis. EGFR overexpression is associated with tumor progression and metastasis, resistance to radiation and chemotherapy, and poor prognosis. Growth factor receptors are regulated by multiple miRNAs, each having many targets, coordinately controlling the complex pathways of downstream signaling. We have previously reported a post-transcriptional mechanism by which BRCA1 regulates EGFR expression through the induction of miR-146a and provided a rationale for the development of miR-146a based therapeutic strategies. In addition, we have shown that BRCA1 also exerts regulatory control over dozens of important miRNAs that appear to play a critical role in breast neoplasia. From TCGA analysis, we show that low expression of these miRNAs is associated with distinctively poor overall survival of TNBC patients. Using miR-146a loss or gain of function experiments in vitro, we show that BRCA1 and miR-146a regulate EGFR signaling, stemness, epithelial-to-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling and chemoresistance. Using in vivo mouse models, we demonstrate that miR-146a overexpression delays tumor formation leading to better overall survival. BLBC unlike the other subtypes, lacks targeted therapy approaches making cytotoxic chemotherapy essentially the only option for treatment. Though EGFR inhibitors have been used to treat other cancers, clinical trials for breast cancer have so far been unsuccessful due to poor response rates. Since one miRNA can target multiple genes and regulate multiple signaling pathways, our study provides evidence to suggest that restoring miR-146a could suppress EGFR-RAS-MEK signaling and the other compensatory pathways, providing a targeted therapeutic option for BRCA1 associated BLBC. Citation Format: Easwari Kumaraswamy, Raeann M. Koren Shimak, Sumedha Gunewardena, Karen L. Wendt, Dani Alexander, Stacey L. Hembruff, Roy A. Jensen. Regulation of epidermal growth factor receptor signaling by BRCA1-microRNA 146a network [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2998.

Abstract 1000: Clinician and clinical trial staff perspectives on factors that impact enrollment of Black women in breast cancer trials

Abstract Background: Black women (BW) are more likely to present with advanced-stage disease and to die following a breast cancer (BC) diagnosis compared with women from other racial and ethnic groups, yet BW are underrepresented in BC clinical trials (CT). Clinicians and CT staff play a key role in patient participation in CT, however, there is limited data on their perspectives on facilitators and barriers for BW in BC trials. Objective: The goal of the FOR ME (Fostering Opportunities in Research through Messaging and Education) study is to develop, optimize, and test a decision-aid intervention (web-based video) for clinical care teams to use with BW who have been recently diagnosed with BC to promote shared decision-making and CT participation. We provide insight into the facilitators and barriers from clinicians and CT staff to effectively discuss and enroll BW in BC trials. The identified themes will be used to inform video content and dissemination strategies. Methods: Key informant interviews (KIIs) (n=20) were conducted by phone and video conferencing. Each KII was recorded and professionally transcribed. Thematic analysis and inductive coding approaches were used to analyze the data. First, a subset of transcripts was annotated, and then annotations were compiled into a preliminary codebook. Inter-coder reliability was established to improve quality and to establish the final codebook. Dedoose was used to analyze quotations and code co-occurrences, application frequencies, and relationships. Results: In total, 16 clinicians and 4 clinical trial staff across academic and community practices were interviewed. Participants expressed multiple opportunities and barriers to CT participation. Facilitators included formal training on communication around clinical trials among clinical trial staff, previous exposure to discussing and enrolling patients in CT during fellowships and other training, institutional support for CT databases, reviewing CTs during tumor boards, and the presence of dedicated research support staff. Barriers included a lack of formal training in communicating CT to patients among clinicians, lack of institutional investment in CT infrastructure, time constraints of clinical visits, and the clinician’s perception of the patient's willingness and ability to complete a CT. Conclusions: Clinicians and clinical trial staff have a unique and important role to play in CT participation for BW who have BC, however, there are barriers, including training, time, awareness of available trials, and institutional support. Clinical trial staff report formal training in communicating clinical trial information to patients, while there is a lack of this type of training for clinicians. Future research in the FOR ME study will integrate patient, clinician, care team, and advocate perspectives into a web-based decision aid. Citation Format: Christen Sandoval, Eliza Brumer Cohn, Leslie R. Carnahan, Vida Henderson, Tigist Mersha, Neha Hippalgaonkar, Joe Horowitz, Sarah Khan, Kauthar Salum, Ana Williams, Lolita Coleman, Beluah Brent, Anne Marie Murphy, Paris Thomas, Paramjeet Khosla, Kent Hoskins, Ryan Nguyen. Clinician and clinical trial staff perspectives on factors that impact enrollment of Black women in breast cancer trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1000.

Abstract 6663: Innovative CPMV immunotherapy: A canine model for poor-prognosis breast cancer treatment

Abstract Cowpea Mosaic Virus (CPMV) is a plant comovirus non-infectious to humans or animals. In mice models, intratumor immunotherapy (ITI) with CPMV devoid of nucleic acids (empty CPMV, eCPMV) and full CPMV results in a highly potent, systemic, antitumor immune response, with full CPMV being much more effective. Dogs with spontaneous mammary (breast) cancer (MC) serve as a valuable model for studying breast cancer (BC), bridging the gap between studies in rodents and human clinical trials. Canine MC develops in the presence of an intact immune system and has a unique advantage of shorter endpoint periods compared to women BC clinical trials. New immunotherapeutic approaches are necessary for poor-prognosis BC, such as triple-negative BC, metastatic BC, and the very aggressive and lethal inflammatory BC (IBC). Previous studies by our group using eCPMV ITI in dogs with MC revealed a substantial reduction in tumor size in both injected and non-injected tumors (abscopal effect), extended survival, and improved quality of life without any adverse effects or toxicity. In this clinical trial, we employed full CPMV nanoparticles ITI in dogs with poor-prognosis (inoperable) MC, comparing them with untreated controls. Regular tumor volume assessments and clinical evaluations have been conducted. Histopathology and immunohistochemistry of immune cell populations were performed to study tumor microenvironment (TME) modifications. Thus far, 5 dogs have been treated: four cases of inflammatory mammary cancer (IMC) and one case of metastatic MC. After at least two weekly CPMV ITI sessions, a significant reduction in tumor volumes was observed. In IMC cases, marked clinical improvement of typical signs (warmth, edema, erythema, and cutaneous pain) was observed in 3 out of 4 cases, and tumor reduction was so remarkable in one dog that surgery was recommended and successfully carried out. In IMC CPMV ITI cases, the survival of 2 dogs exceeded historical IMC records; the dog with metastatic MC maintains stable disease after one year, which is also superior to controls. TME studies showed that eCPMV immunotherapy significantly increased intratumor inflammatory infiltrates, neutrophils, T lymphocytes, and macrophages. Additionally, Treg cells (FOXP3+)/T lymphocytes (CD3+) ratio was significantly reduced. Our results demonstrate that immunotherapy with eCPMV induces a potent immunostimulatory effect on dogs with poor-prognosis MC by recruiting and activating neutrophils as the main drivers of the inflammatory response. This process reduces the immunosuppressive action of regulatory T lymphocytes and produces a breakdown of tumor immune suppression. These findings underscore the therapeutic potential of CPMV nanoparticles ITI in the management of canine IMC and metastatic MC. From a translational point of view, this study lays the groundwork for advancing the treatment of human breast cancer. Citation Format: Guillermo Valdivia, Dolores Pérez-Alenza, Lucía Barreno, Ángela Alonso-Diez, Jessica Fernanda Affonso de Oliveira, María Suárez-Redondo, Steven F. Fiering, Nicole F. Steinmetz, Laura Peña. Innovative CPMV immunotherapy: A canine model for poor-prognosis breast cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6663.

CDK4/6i-treated HR+/HER2- breast cancer tumors show higher ESR1 mutation prevalence and more altered genomic landscape

As CDK4/6 inhibitor (CDK4/6i) approval changed treatment strategies for patients with hormone receptor-positive HER2-negative (HR+/HER2-) breast cancer (BC), understanding how exposure to CDK4/6i affects the tumor genomic landscape is critical for precision oncology. Using real-world data (RWD) with tumor genomic profiling from 5910 patients with metastatic HR+/HER2- BC, we investigated the evolution of alteration prevalence in commonly mutated genes across patient journeys. We found that ESR1 is more often altered in tumors exposed to at least 1 year of adjuvant endocrine therapy, contrasting with TP53 alterations. We observed a similar trend after first-line treatments in the advanced setting, but strikingly exposure to aromatase inhibitors (AI) combined with CDK4/6i led to significantly higher ESR1 alteration prevalence compared to AI alone, independent of treatment duration. Further, CDK4/6i exposure was associated with higher occurrence of concomitant alterations in multiple oncogenic pathways. Differences based on CDK4/6i exposure were confirmed in samples collected after 2L and validated in samples from the acelERA BC clinical trial. In conclusion, our work uncovers opportunities for further treatment personalization and stresses the need for effective combination treatments to address the altered tumor genomic landscape following AI+CDK4/6i exposure. Further, we demonstrated the potential of RWD for refining patient treatment strategy and guiding clinical trial design.

Current status of optoacoustic breast imaging and future trends in clinical application: is it ready for prime time?

Optoacoustic imaging (OAI) is an emerging field with increasing applications in patients and exploratory clinical trials for breast cancer. Optoacoustic imaging (or photoacoustic imaging) employs non-ionizing, laser light to create thermoelastic expansion in tissues and detect the resulting ultrasonic emission. By combining high optical contrast capabilities with the high spatial resolution and anatomic detail of grayscale ultrasound, OAI offers unique opportunities for visualizing biological function of tissues in vivo. Over the past decade, human breast applications of OAI, including benign/malignant mass differentiation, distinguishing cancer molecular subtype, and predicting metastatic potential, have significantly increased. We discuss the current state of optoacoustic breast imaging, as well as future opportunities and clinical application trends. CLINICAL RELEVANCE STATEMENT: Optoacoustic imaging is a novel breast imaging technique that enables the assessment of breast cancer lesions and tumor biology without the risk of ionizing radiation exposure, intravenous contrast, or radionuclide injection. KEY POINTS: • Optoacoustic imaging (OAI) is a safe, non-invasive imaging technique with thriving research and high potential clinical impact. • OAI has been considered a complementary tool to current standard breast imaging techniques. • OAI combines parametric maps of molecules that absorb light and scatter acoustic waves (like hemoglobin, melanin, lipids, and water) with anatomical images, facilitating scalable and real-time molecular evaluation of tissues.

Psychosocial Factors That Influence a Woman's Decision to Enroll in a Clinical Trial: Implications on How to Improve Clinical Trial Enrollment Among Black Women

Black women with breast cancer often present with more aggressive disease compared with other races, contributing to an increased risk of cancer mortality. Despite this inequity, Black women remain severely underrepresented in breast cancer clinical trials. We aim to characterize factors that influence a woman's decision to enroll in a clinical trial, with the goal of identifying clinical interventions to aid in the recruitment of vulnerable groups. A cross-sectional, descriptive study was conducted using a questionnaire adapted from 2 prevalidated surveys investigating factors influencing clinical trial enrollment. The survey was administered to women with curable breast cancer during a single follow-up visit at 4 different sites within a university medical system where all patients are screened for clinical trial eligibility. Chi-square tests and Mann-Whitney U tests were used to assess associations or differences between the populations. One hundred ninety-four out of 209 women completed the survey, giving a compliance rate of 93%. Twenty-six percent of women self-identified as Black, most women were located at community sites (67.1%), most women had diagnoses of early-stage disease (I: 57.7%, II: 29.4%), and 81% of women had some collegiate-level education. Black women were younger at diagnosis (P = .005) and less likely to be married (P = .012) but more often lived with family members (P = .003) and had a lower median income (P < .001). According to the survey, Black women were less likely to trust their care team (P = .032), more likely to believe that research ultimately harms minorities (P < .001), and had a stronger belief in God's will determining illness and wellness (P < .001). Recurring themes of trust in the health care team, patient education, and advancement of cancer treatments were discussed in the focus groups. Failure to offer clinical trials and mistrust in research institutions may pose the greatest hindrances to the enrollment of Black women in clinical trials. Empowering women through education and fostering trustworthy relationships can encourage greater clinical trial participation.