A groundbreaking study led by researchers at Roswell Park Comprehensive Cancer Center has unveiled critical genomic insights into triple-negative breast cancer (TNBC) in African American women. Published in Nature Genetics on March 15, 2024, this research addresses a significant gap in genomic studies, as African American women have historically been underrepresented in this area.
The study, titled “Mutational Landscape of Triple-Negative Breast Cancer in African American Women,” involved a comprehensive analysis of genetic data from 462 African American women diagnosed with TNBC. This research utilized whole-exome and RNA sequencing technologies, resulting in the largest and most detailed mutational profile of this demographic to date. The findings revealed that the mutational patterns in African American women were largely consistent with those observed in Asian American and non-Hispanic white women, indicating no significant association with African ancestry.
One of the notable discoveries was the prevalence of mutations in the TP53 gene, which were found in nearly all participants. Dr. Song Yao, the lead author and Professor of Oncology at Roswell Park, emphasized the implications of the study: “There is a long-standing question in the field of TNBC epidemiology regarding whether the disproportionately high incidence of TNBC in African American women stems from different cancer biology or socio-environmental exposures. Our data do not support major racial differences in TNBC biology at the level of somatic mutations.”
Key Findings and Implications
The research team identified two primary pathways contributing to TNBC development in African American women. The first pathway, more prevalent among younger patients, is linked to genetic predispositions and deficiencies in DNA damage repair. The second, occurring more frequently in older patients, is associated with aging and obesity. Dr. Yao remarked on this duality: “This is quite fascinating! While we often connect TNBC with deficiencies in DNA damage repair in younger women, our findings suggest that aging and obesity may also significantly influence TNBC development.”
The study’s success stemmed from a collaborative effort involving several esteemed institutions. Alongside Dr. Yao, key contributors included Dr. Christine Ambrosone, Senior Vice President of Population Sciences at Roswell Park, and collaborators such as Dr. John Carpten from City of Hope Comprehensive Cancer Center, Dr. Wei Zheng from Vanderbilt-Ingram Cancer Center, and Dr. Julie Palmer from Slone Epidemiology Center at Boston University.
The bioinformatics analysis, crucial for managing the extensive data, was led by Dr. Song Liu, Vice Chair of Biostatistics and Bioinformatics at Roswell Park, alongside colleagues Dr. Lei Wei and Dr. Qiang Hu. The research was made possible through the pooling of resources from the Women’s Circle of Health Study (WCHS), the Black Women’s Health Study (BWHS), and the Southern Community Cohort Study (SCCS), with invaluable contributions from patient volunteers across the nation.
Funding for the study was provided by the National Institutes of Health, the Roswell Park Cancer Center Support Grant, the Breast Cancer Research Foundation, and the Karin Grunebaum Cancer Research Foundation.
This landmark study not only enhances the understanding of TNBC in African American women but also sets the stage for future research aimed at improving treatment strategies and outcomes for this vulnerable population.
