Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer and significantly impacts African American women, who face a higher incidence of this disease. A pivotal study spearheaded by researchers at Roswell Park Comprehensive Cancer Center addresses this important issue by exploring the genetic factors relevant to TNBC in this demographic. The lead author, Dr. Song Yao, MD, PhD, along with a team of collaborators, published their findings in the esteemed journal Nature Genetics.
Through comprehensive whole-exome and RNA sequencing, the researchers established an extensive mutational profile derived from 462 African American women diagnosed with TNBC. The analysis revealed that the mutational landscape in this group closely aligns with that found in Asian American and non-Hispanic white women. Notably, the study found no significant correlation between African ancestry and the specific genetic mutations observed.
“There is a long-standing question in the field of TNBC epidemiology of whether the disproportionately high incidence of TNBC in African American women is a result of different cancer biology or socio-environmental exposures. Our data do not support major racial differences in TNBC biology at the level of somatic mutations, which are not inherited but acquired by cancer cells during disease development and progression,”
Dr. Song Yao, MD, PhD, Professor of Oncology, Roswell Park
Additionally, the study identified two predominant pathways contributing to disease development within this population. One pathway, prevalent among younger patients, relates to genetic predispositions and deficiencies in DNA repair mechanisms. Conversely, the second pathway, often seen in older patients, is associated with factors such as aging and obesity. Dr. Yao remarked, “This is quite fascinating! We tend to link TNBC with deficiency in DNA damage repair and with younger women, but now we see evidence that aging and obesity may play a role in the development of TNBC as well.”
The success of this study was facilitated through a collaborative effort involving multiple institutions, including contributions from Christine Ambrosone, PhD, and other distinguished researchers, such as John Carpten, PhD, at City of Hope Comprehensive Cancer Center and Wei Zheng, MD, PhD, MPH, at Vanderbilt-Ingram Cancer Center. The bioinformatics analysis was expertly managed by Song Liu, PhD, MBA, and colleagues at Roswell Park.
Data for this landmark study was aggregated from several important sources, including the Women’s Circle of Health Study (WCHS), the Black Women’s Health Study (BWHS), and the Southern Community Cohort Study (SCCS), which involved patient volunteers from across the United States who generously contributed their time, efforts, and biological samples.
Funding for the research was provided by key organizations and grants, including the National Institutes of Health, the Roswell Park Cancer Center Support Grant, the Breast Cancer Research Foundation, and the Karin Grunebaum Cancer Research Foundation.
Source:
Roswell Park Comprehensive Cancer Center
Journal reference:
Yao, S., et al. (2025). Mutational landscape of triple-negative breast cancer in African American women. Nature Genetics. doi.org/10.1038/s41588-025-02322-y
