Genetic Analysis of Triple-Negative Breast Cancer in African American Women Shows No Ancestral Link to Disease

Triple-negative breast cancer (TNBC), the most fatal subtype of breast cancer, disproportionately impacts African American women—yet they have been underrepresented in genomic research aimed at pinpointing the genetic mutations responsible for this disease until now.

A study directed by researchers at Roswell Park Comprehensive Cancer Center and collaborating institutions addresses this gap. Song Yao, MD, Ph.D., a Professor of Oncology at Roswell Park, is the lead author of a study titled "Mutational Landscape of Triple-Negative Breast Cancer in African American Women," published in Nature Genetics.

Using whole-exome and RNA sequencing, researchers created the largest and most comprehensive mutational profile for 462 African American women with TNBC. The results were largely similar to those of Asian American and non-Hispanic white women, with no evidence linking the mutations to African ancestry. The team discovered that mutations in the TP53 gene were present in nearly all African American TNBC patients—found more widely than previously thought.

"We have long questioned whether the higher incidence of TNBC in African American women is due to different cancer biology or socio-environmental factors," says Dr. Yao. "Our data suggest that there are no significant racial differences in TNBC's biology at the level of somatic mutations, which arise during disease development and progression rather than being inherited."

The researchers identified two primary pathways for disease development within this population. One pathway, more common among younger patients, relates to genetic predisposition and flawed DNA damage repair; the other, found primarily in older patients, is associated with aging and obesity-related factors.

"This discovery is intriguing," says Dr. Yao. "While TNBC is typically linked with impaired DNA damage repair and younger women, we now see evidence that aging and obesity may also contribute to TNBC development."

This research resulted from collaboration among investigators at Roswell Park, including Christine Ambrosone, Ph.D., Senior Vice President of Population Sciences, as well as several other institutions. Key contributors include John Carpten, Ph.D., at City of Hope Comprehensive Cancer Center; Wei Zheng, MD, Ph.D., MPH, at Vanderbilt-Ingram Cancer Center; and Julie Palmer, ScD, at Slone Epidemiology Center, Boston University. The Bioinformatics team at Roswell Park led by Song Liu, Ph.D., MBA, Vice Chair, Biostatistics and Bioinformatics, along with colleagues Lei Wei, Ph.D., and Qiang Hu, MD, Ph.D., handled the bioinformatics analysis of the extensive dataset.

The study was made possible through pooled resources from the Women's Circle of Health Study (WCHS), Black Women's Health Study (BWHS), and Southern Community Cohort Study (SCCS). Patient volunteers across the country contributed their time, efforts, and samples to this research effort.