Genomic Analysis Shows Triple-Negative Breast Cancer in African American Women Is Not Linked to Ancestry

Recent genomic research focusing on triple-negative breast cancer (TNBC), a particularly aggressive subtype of breast cancer, has provided new insights into its development in African American women. Historically, African American women have experienced higher incidence rates of TNBC, but whether this was due to genetic differences or social and environmental factors remained unclear.

A comprehensive study led by researchers at Roswell Park Comprehensive Cancer Center involved analyzing the genetic mutations of 462 African American women diagnosed with TNBC. Using whole-exome and RNA sequencing, the study generated the largest and most detailed mutational profile of this population. Findings revealed that the genetic mutation patterns in African American women with TNBC closely resemble those of Asian American and non-Hispanic white women. Importantly, there was no evidence linking the disease to African ancestry, challenging previously held assumptions.

A notable discovery was the near-universal presence of TP53 gene mutations among the African American TNBC patients, which was more prevalent than earlier believed. This suggests common biological pathways may be involved across different racial backgrounds, nullifying the idea that TNBC’s aggressive nature is solely driven by race-associated genetics.

The study also identified two primary pathways involved in the disease’s development. One pathway, more common among younger women, involves genetic predisposition and impaired DNA damage repair mechanisms. The other pathway, observed more frequently in older women, relates to aging processes and the impacts of obesity.

Dr. Yao emphasized that these findings indicate that biological differences at the level of somatic mutations are minimal across races. Instead, factors like aging and obesity might play significant roles in the development of TNBC, shifting focus away from race-based genetic explanations.

This study was made possible through collaboration among multiple institutions, including contributions from bioinformatics teams and large cohort studies such as the Women’s Circle of Health Study, the Black Women’s Health Study, and the Southern Community Cohort Study. The research highlights the importance of inclusive genomic studies and provides a pathway for more targeted approaches to treatment and prevention.

For more details, see the full study: Song Yao et al, "Mutational Landscape of Triple-Negative Breast Cancer in African American Women," published in Nature Genetics (2025).