Unraveling the biology of TNBC in African American women through the WHITNEY study.

Abstract Cancer disparities arise from structural racism in the United States, which affects overall standard of living due to unequal access to crucial resources. Barriers in access to clinical care among under-served populations in combination with a vast underrepresentation at a scientific research level further perpetuate inequalities in cancer treatment. Specifically, Black women in the US are approximately twice as likely as Caucasian women to die of Triple-Negative Breast Cancer (TNBC), a particularly aggressive breast cancer subset, lacking expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor-2. Our previous work and that of others has shown racial differences in TNBC tumor biology, with preference of basal-like subtypes in African American (AA) women. Herein, we present the Women’s Health Initiative for Triple-Negative Breast Cancer Equity (WHITNEY) study, a first of its kind, coordinated effort between Massachusetts General Hospital, and Boston Medical Center, the largest safety-net hospital in New England. The WHITNEY study seeks to understand factors contributing to biological differences and outcome of TNBC diagnoses in AA women. Response to neoadjuvant chemotherapy (NACT) response is a strong predictor of TNBC outcomes and failure to achieve a pathological complete response (pCR) in the breast following NACT is associated with a high probability of metastatic relapse. As Black women with TNBC have lower pCR rates, WHITNEY has collected pre-treatment biopsies from AA and other TNBC patients undergoing NACT to understand actionable insights into the biological differences in TNBC. Our prior published work has suggested that intratumoral heterogeneity is greater in TNBCs among AA patients than others, and that epigenetic silencing of key tumor suppressors is selectively increased in these TNBCs. Core needle baseline biopsies were obtained from consented patients diagnosed with TNBC at either MGH or BMC. We utilized single-cell RNA sequencing, spatial transcriptomics, genomic and epigenetic profiling to characterize minor cell subpopulations that drive poor outcomes among African American TNBC patients. Here, we outline our preliminary tissue collection, processing and analysis methods used in the WHITNEY study to better understand the biology of TNBC in African American women. Citation Format: Malalage N. Peiris, Emma Kelly, Christina Ennis, Kiana Mahdaviani, Aylin Dedeoglu, Adrian Ilinski, Esther Rheinbay, Ruben Dries, Naomi Ko, Leif Ellisen. Unraveling the biology of TNBC in African American women through the WHITNEY study [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C051.