Genomic Analysis Reveals Racial and Age-Related Differences in the Somatic Landscape of Breast Cancer and the...

Cancer genomics consortia have identified somatic drivers of breast cancer subtypes. However, these studies have predominantly included older, non-Black women, and the related socioeconomic status (SES) data are limited. Increased representation and depth of social data are crucial for understanding how health inequity is intertwined with somatic landscapes. Here, we conducted targeted sequencing on primary tumors from the Carolina Breast Cancer Study (N = 357; 52% Black; 47% <50) and compared the results with The Cancer Genome Atlas (N = 948; 18% Black; 27% <50). Race (Black vs. non-Black), age, and SES were evaluated in association with mutations, copy number alterations, and aneuploidy using generalized linear models. Pathway dysfunction was also assessed by aggregating mutation and copy number alterations. Adjusting for age, Black participants (N = 350) were significantly more likely to have TP53 and FAT1 mutations and less likely to have PIK3CA, CDH1, DDR2, and GATA3 mutations than non-Black participants. Younger participants had more GATA3 alterations and fewer KMT2C, PTEN, MAP3K1, and CDH1 alterations. Black participants had significant enrichment for MYC (8q) and PIK3CA (3q26) amplifications and higher total aneuploidy, but age was not associated with copy number variation. SES was associated with different patterns of alteration in Black versus non-Black women. Overall, Black participants showed modest differences in TP53, PIK3CA, and other alterations that further varied by SES. Race is a social construct, and varying distributions of etiologic factors across social strata may predispose Black, young, and low SES women to cancer subtypes characterized by these alterations. Significance: The collection and analysis of DNA sequencing with comprehensive socioeconomic factor associations in a large Black breast cancer patient cohort could help uncover mechanisms by which social conditions contribute to tumor biology.