Abstract B107: Race-specific gene expression patterns in triple-negative breast cancer (TNBC) cases

Abstract

Abstract Historically, incidence rates of breast cancer (BC) have been higher among Caucasian (CA) women compared to African-American (AA) women, until convergence of these rates in the mid 2000s. Conversely, when accessing mortality rates among these women, AA women have reported higher rates of mortality from BC since the mid 1980s. Despite a decline in BC mortality over the past 30 years, the mortality rate of disease among AA women remains to be significantly higher than that of their CA counterparts. When molecular subtypes of BC are considered, prevalence of Triple-Negative BC (TNBC), the most aggressive subtype of BC, is found to be higher among AA women. TNBC prevalence on the global scale shows highest levels of TNBC across Africa, and higher rates can also be observed across the African diaspora. To address this, we sought out to identify race-specific differences among TNBC cases. We completed RNA sequencing on a cohort of 75 cases, where 42 of the cases were AA, and 33 were CA. The dataset was dichotomized by if the individuals had received neoadjuvant chemotherapy prior to surgery and specimen collection, where we had 60 treatment naïve cases (31 AAs and 29 CAs) and the remaining 15 had received neoadjuvant chemotherapy (residual tumors; 11 AAs and 4 CAs). We assessed self-reported race, ancestry estimation from matched DNA samples into and TNBC molecular subtyping from matched DNA samples into our DE gene expression analyses. Among treatment naïve tumors, we identified over 1000 genes that were significantly differentially expressed (DE) between race groups (p < 0.05). To further analyze our race-specific gene set, we used Ingenuity Pathway Analysis (IPA) to investigate relevant pathways and regulators specific to our gene set. Using the causal network analysis, we see that biological functions such as cellular organization and assembly show significant enrichment in our gene set, and that the NFkB complex is a top regulator predicted to be activated in our AA treatment naïve cases compared to CAs. For those individuals who had received neoadjuvant chemotherapy, we identified 13 genes that are significantly different between race groups, and these DE genes are distinct from those identified in our treatment naïve analyses. Citation Format: Rachel Martini, Jason White, Akanksha Verma, Olivier Elemento, Lisa Newman, Manne Upender, Clayton Yates, Melissa Davis. Race-specific gene expression patterns in triple-negative breast cancer (TNBC) cases [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B107.