Race and Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative, Node-Positive Breast Cancer in the Randomized RxPONDER Trial

Abstract

Background The phase III RxPONDER trial has impacted treatment for node-positive(1-3), hormone receptor-positive, HER2-negative breast cancer with 21-gene recurrence score (RS) ≤ 25. We investigated how these findings apply to different racial and ethnic groups within the trial. Methods The trial randomized women to endocrine therapy (ET) or to chemotherapy plus ET. The primary clinical outcome was invasive disease-free survival (IDFS) with distant relapse-free survival (DRFS) as a secondary outcome. Multivariable Cox models were used to evaluate the association between race/ethnicity and survival outcomes, adjusting for clinicopathologic characteristics, RS, and treatment. Results A total of 4,048 women with self-reported race/ethnicity were included: Hispanic (15.1%), non-Hispanic Black (NHB)(6.1%), Native American/Pacific Islander (0.8%), Asian (8.0%), and non-Hispanic White (NHW)(70%). No differences in RS distribution, tumor size, or number of positive nodes were observed by race/ethnicity. Relative to NHWs, IDFS was worse for NHBs (5-year IDFS 91.6% vs 87.1%, HR = 1.37; 95% CI 1.03-1.81) and better for Asians (91.6% vs 93.9%, HR = 0.64; 95% CI 0.46-0.91). Relative to NHW, DRFS was worse for NHBs (5-year DRFS 95.8% vs 91.0%, HR = 1.65; 95% CI 1.17-2.32) and better for Asians (95.8% vs 96.7%, HR = 0.59; 95% CI 0.37-0.95). Adjusting for clinical characteristics, particularly body mass index, diminished the effect of race on outcomes. Chemotherapy treatment efficacy did not differ by race/ethnicity. Conclusions NHB women had worse clinical outcomes compared to NHWs in the RxPONDER trial despite similar RS and comparable treatment. Our study emphasizes the persistent racial disparities in breast cancer outcomes while highlighting complex interactions among contributing factors. Trial Registration ClinicalTrials.gov: NCT01272037