Abstract SY45-01: Exploring the TNBC landscape to reduce racial disparities: Actionable insights from AR
Authors: Aneja Ritu 
Published: August 2018

Triple-negative breast cancer (TNBC) is an aggressive breast cancer (BC) subtype for which no targeted therapies have been approved yet. African-American (AA) BC patients are 2-3X more likely to have TNBC than their European-American (EA) counterparts. TNBC can be subdivided into androgen receptor-positive (AR+) and androgen receptor-negative (AR- or quadruple-negative) subtypes. Recently, AR has emerged as a potential new drug target for TNBC. While AR+ TNBC responds to AR antagonists currently in development, unfortunately, no targeted drugs are available or under development for the AR- TNBC (QNBC) subgroup. The prognostic value of AR in TNBC is highly controversial owing to conflicting results from studies that often do not take into consideration patients' biogeographic ancestry and use different antibodies or cut-points for analyses. To reconcile conflicting reports about the impact of AR status on long-term prognosis of TNBC after adjuvant chemotherapy, we determined the prognostic value of AR in diverse TNBC cohorts from different countries. We evaluated AR expression in well-annotated formalin-fixed, paraffin-embedded TNBC resection samples (n=1251) from multiple institutions (six hospitals in the US [n=424], Olabisi Onabanjo University, Nigeria [n=79], Stavanger University Hospital, Norway [n=104], NUI Galway, Ireland [n=244], Nottingham University Hospital, UK [n=164], and two hospitals in India [n=242]). All samples were stained with the same antibody and centrally reviewed. Samples with &lt;1% nuclei staining positive for AR were deemed to be QNBC. Associations between TNBC/QNBC status, clinicopathologic variables, and overall survival were sought. Our multi-institutional study uncovered that women with African ancestry, including AAs, are predisposed to developing QNBC. Among patients who received adjuvant chemotherapy in the US, QNBCs had poorer long-term outcomes than TNBCs. By contrast, adjuvant chemotherapy-treated QNBCs had better long-term outcomes than AR-positive TNBCs in the Norwegian, Irish, and Indian cohorts. In both these opposing situations, AR status retained its statistically significant prognostic value after adjustment for potentially confounding variables. Our results suggest that population-specific factors beyond the expression status of full-length AR impact patient prognosis in TNBC. Our study thus suggests that oncogenic Wnt/β-catenin signaling may link AR loss to more aggressive disease course especially among AA patients, and may represent actionable biology in AA QNBCs. Studies examining factors that determine the prognostic impact of AR status in racially distinct TNBCs/QNBCs and to identify actionable targets in QNBC are currently under way in our laboratory.

Citation Format: Ritu Aneja. Exploring the TNBC landscape to reduce racial disparities: Actionable insights from AR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr SY45-01.