Abstract
Abstract African American (AA) estrogen receptor positive (ER+) breast cancer patients have worse outcomes than Caucasian Americans (CA) being 42 % more likely to die from the disease. However, AAs are severely underrepresented in currently available datasets of patient tumors, which precludes comprehensive approaches to identify race-specific molecular drivers of these poor outcomes. Endocrine therapy (ET) is the first line standard of care for ER+ breast cancer. Nevertheless, 1 in 4 patients develop ET resistance. Specific DNA damage/repair (DDR) defects have been shown to associate with poor outcome in CA patients, and to induce ET resistance. Whether these or other DDR defects contribute to poor outcomes observed in AA patients remains unknown. For the purpose of this investigation, we assessed the DDR dysregulation landscape of AA ER+ tumors using three independent tumor datasets (1) GSE78958 (2) GSE18229 (3) The Cancer Genome Atlas (TCGA) and two normal breast datasets (1) GSE43973 (2) GSE50939. This analysis identified a distinct set of AA ER+ tumors with simultaneous dysregulation of genes from multiple DDR pathways, rarely seen in CA tumors. This simultaneous dysregulation also associated with worse patient outcomes in all three datasets analyzed. This work constitutes the first systematic analysis of race-specific DDR dysregulation in ER+ breast cancer, and identifies DDR as a potential predictive biomarker for worse outcome seen in AA patients. Citation Format: Aloran Mazumder, Athena Jimenez, Rachel Ellsworth, Stephen Freedland, Sophia George, Matthew Bainbridge, Svasti Haricharan. Race specific differences in DNA damage repair dysregulation in breast cancer and association with outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2521.