Impact of Genetic Ancestry on Outcomes in ECOG-ACRIN-5103

Abstract

Purpose Racial disparity in breast cancer outcomes exists between African American and white women in the United States. We have evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for patients with breast cancer in the context of a randomized, phase III adjuvant trial. Methods This study compared outcomes between 386 patients of African ancestry (AA) and 2,473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial, ECOG-ACRIN-5103. The primary efficacy end point, invasive disease–free survival (DFS), and clinically significant toxicities were compared, including anthracycline-induced congestive heart failure, taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension. Results Overall, AAs had significantly inferior DFS ( P = .002; hazard ratio, 1.5) compared with EAs. This was significant in the estrogen receptor–positive subgroup ( P = .03), with a similar, nonsignificant trend for those who had triple-negative breast cancer ( P = .12). AAs also had significantly more grades 3 to 4 TIPN (odds ratio [OR], 2.9; P = 2.4 × 10−11) and grades 3 to 4 bevacizumab-induced hypertension (OR, 1.6; P = .02), with a trend for more congestive heart failure (OR, 1.8; P = .08). AAs had significantly more dose reductions in paclitaxel ( P = 6.6 × 10−6). In AAs, dose reductions in paclitaxel had a significant negative impact on DFS ( P = .03), whereas in EAs, dose reductions did not have an impact on outcome ( P = .35). Conclusion AAs had inferior DFS, with more clinically important toxicities, in ECOG-ACRIN-5103. The altered risk-to-benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions in paclitaxel, especially as the result of TIPN, are warranted for this population.