West African Genetic Ancestry and Breast Cancer Outcomes Among Black Women.

Importance: Young Black women bear a disproportionate burden of breast cancer deaths compared with White women, yet they remain underrepresented in genomic studies.

Objective: To evaluate the association of biological factors, including West African genetic ancestry, and nonbiological factors with disease-free survival (DFS) among young Black women with breast cancer.

Design, Setting, And Participants: This observational cohort study included Black women diagnosed with invasive breast cancer between January 1, 2005, and December 31, 2016. Participants diagnosed with breast cancer at age 50 years or younger were recruited through the Florida and Tennessee state cancer registries. The final analysis was completed between June and September 2024.

Exposure: West African genetic ancestry.

Main Outcomes And Measures: A multivariable model was developed to evaluate the association between West African genetic ancestry and breast cancer DFS, adjusting for immunohistochemistry subtype, lymph node (LN) status, and full-time employment.

Results: This study included 687 Black women with early-stage invasive breast cancer. Their median age at diagnosis was 44 years (IQR, 38-47 years), and the median follow-up was 10 years (IQR, 7-11 years). In multivariable analysis, triple-negative breast cancer (TNBC) and LN involvement were associated with shorter breast cancer DFS (hazard ratio, 1.81 [95% CI, 1.20-2.73] and 1.77 [95% CI, 1.30-2.41], respectively), whereas full-time employment was associated with improved outcomes (hazard ratio, 0.44 [95% CI, 0.30-0.63]). Among the 551 participants for whom global genetic ancestry could be assessed, having a higher percentage of West African genetic ancestry was associated with shorter breast cancer DFS among 246 participants in the hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (ERBB2 [formerly HER2])-negative subgroup (hazard ratio, 1.45 [95% CI, 1.04-2.04]). Of the 369 participants (53.7%) with PAM50 data available, basal (133 [36.0%]) and luminal B (107 [29.0%]) subtypes were the most common. Among the 179 patients with HR-positive/ERBB2-negative disease and PAM50 data available, luminal B and basal subtypes combined were also overrepresented (81 [45.3%] and 24 [13.4%], respectively) compared with luminal A (70 [39.1%]).

Conclusions And Relevance: In this study of young Black women with breast cancer, having a higher percentage of West African genetic ancestry, TNBC, and LN involvement were associated with shorter breast cancer DFS. Interestingly, full-time employment was associated with improved breast cancer DFS. These findings highlight the importance of considering genetic ancestry beyond self-reported race and accounting for social determinants of health, in efforts to improve survival outcomes among Black women with breast cancer.