Abstract C033: Racial differences in the associations between luminal master regulator transcription factor expression and breast cancer survival

Purpose: Women of African ancestry in the United States are more likely to die from breast cancer than their European counterparts. While prior studies suggest differences in the frequency of hormone receptor-negative disease as an underlying cause, recent studies report higher race-based mortality rates in patients with hormone receptor-positive, luminal breast cancer. Here we explore biologic factors that may underly this disparity by comparing racial differences in the level, functional activity, and prognostic significance of 3 master transcriptional regulators of mammary luminal differentiation. Patients and Methods: Medical records and tissues from 555 patients (293 European and 262 African ancestry) diagnosed with Stage 0 to IV breast cancer, from 2001 to 2010 at a major medical center in East North Carolina, were analyzed for the expression of functional biomarkers of luminal differentiation including estrogen receptor (ESR1), and pioneer transcription factors FOXA1 and GATA3. Differential comparison of protein expression was integrated with network-level gene expression analysis (22% of cohort) to define predictive correlations with race and survival. Results: Univariate and multivariate odds ratios combined with area under the curve receiver operator characteristics show significant differences in predictive activity of these functional biomarkers based on race and survival—ESR1 (EA OR= 0.47, p = 5e-04; AA OR= 0.77, p = 0.22), FOXA1 (EA OR= 0.38, p= 1.4e-04; AA OR = 0.53, p = 1.3e-02), and GATA3 (EA OR= 0.36, p= 3.7e-06, AA OR= 0.57, p= 0.51)—and uncover genes in the downstream regulons of these biomarkers that strongly correlate either with genetic ancestry or overall survival. Conclusion: Transcriptional regulatory networks linked to mammary luminal differentiation reveal race-specific differences in master regulatory activity that may underlie tumor characteristics contributing to racial disparities in outcome. These biomarkers and their downstream regulons represent important targets to explore intrinsic mechanisms that drive breast cancer survival disparities. Citation Format: Jung S. Byun, Sandeep K. Singhal, Sam Park, Dae Ik Yi, Tingfen Yan, Ambar Caban, Alana Jones, Partha Mukhopadhyay, Sara Gil Hernandez, Stephen Hewitt, Lisa A. Newman, Melissa Davis, Jorge Sepulveda, Adrianna De Siervi, Anna Napoles, Nasreen Vohra, Kevin Gardner. Racial differences in the associations between luminal master regulator transcription factor expression and breast cancer survival [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C033.