Comparison of the genomic landscape between primary breast cancer in African American versus white women and the association of racial differences with tumor recurrence

Abstract

Purpose: African American women are more likely to die as a result of breast cancer than white women. The nfluence of somatic genomic profiles on this racial disparity is unclear. We aimed to compare the racial distribution of tumor genomic characteristics and breast cancer recurrence. Methods: We assessed white and African American women with stage I to III breast cancer diagnosed from 1988 to 2013 and primary tumors submitted to The Cancer Genome Atlas from 2010 to 2014. We used Cox proportional hazards models to evaluate the association of race and genetic traits with tumor recurrence. Results: We investigated exome sequencing and gene expression data in 663 and 711 white and 105 and 159 African American women, respectively. African Americans had more TP53 mutations (42.9% v27.6%; P = .003) and fewer PIK3CA mutations (20.0% v33.9%; P = .008). Intratumor genetic heterogeneity was greater in African American than white tumors overall by 5.1 units (95% CI, 2.4 to 7.7) and within triple-negative tumors by 4.1 units (95% CI, 1.4 to 6.8). African Americans had more basal tumors by the 50-gene set predictor using the predication analysis of microarray method (PAM50; 39.0% v 18.6%; P< .001) and fewer PAM50 luminal A tumors (17.0% v 34.7%; P < .001). Among triple-negative subtypes, African Americans had more basal-like 1 and mesenchymal stem-like tumors. African Americans had a higher risk of tumor recurrence than whites (hazard ratio, 2.22; 95% CI, 1.05 to 4.67). Racial differences in TP53mutation, PAM50 basa subtype, and triple-negative tumor prevalence but not intratumor genetic heterogeneity influenced the magnitude and significance of the racial disparity in tumor recurrence. Conclusion: African Americans had greater intratumor genetic heterogeneity and more basal gene expression tumors, even within triple-negative breast cancer. This pattern suggests more aggressive tumor biology in African Americans than whites, which could contribute to racia disparity in breast cancer outcome.