Landmark study maps mutational landscape of triple-negative breast cancer in African American women

Triple-negative breast cancer (TNBC), the deadliest breast cancer subtype, disproportionately affects African American women – but until now, they were underrepresented in genomic studies aimed at identifying the genetic mutations driving the disease. A landmark study led by researchers at Roswell Park Comprehensive Cancer Center and collaborating institutions fills that knowledge gap. Song Yao, MD, PhD, Professor of Oncology at Roswell Park, is lead author of the study, "Mutational Landscape of Triple-Negative Breast Cancer in African American Women," which appears today in Nature Genetics.

Using whole-exome and RNA sequencing, investigators created the largest and most detailed mutational profile of 462 African American women with TNBC and found it was largely similar to that of Asian American and non-Hispanic white women, with no evidence of association with African ancestry. The team found that mutations in the TP53 gene were present in almost all African American TNBC patients – much more prevalent than previously realized. 

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

The researchers also identified two main pathways of disease development in this population. One, occurring more often in younger patients, is related to genetic predisposition and faulty DNA damage repair; the other, found more often in older patients, is related to aging and the effects of obesity. "This is quite fascinating!" says Dr. Yao. "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."

This study is a result of close collaboration among investigators at Roswell Park, including Christine Ambrosone, PhD, Senior Vice President of Population Sciences, and several other institutions, including John Carpten, PhD, at City of Hope Comprehensive Cancer Center; Wei Zheng, MD, PhD, MPH, at Vanderbilt-Ingram Cancer Center; and Julie Palmer, ScD, at Slone Epidemiology Center, Boston University. The Bioinformatics team at Roswell Park, headed by Song Liu, PhD, MBA, Vice Chair, Biostatistics and Bioinformatics, and colleagues Lei Wei, PhD, and Qiang Hu, MD, PhD, led the bioinformatics analysis of the massive dataset. 

The study was made possible by pooling 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 patient volunteers from across the country who donated their time, efforts and samples. 

The research was funded 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.