A landmark study of the tumor mutational landscape of African American women with triple-negative breast cancer revealed that the mutational profile was largely similar with that of Asian and non-Hispanic White women, except for the presence of TP53 mutations in almost all African American patients, according to genomic findings recently published in Nature Genetics.
"There is a long-standing question in the field of triple-negative breast cancer epidemiology of whether the disproportionately high incidence of triple-negative breast cancer in African American women is a result of different cancer biology or socio-environmental exposures,” stated lead study author Song Yao, MD, PhD, Professor of Oncology, Roswell Park Comprehensive Cancer Center. “Our data do not support major racial differences in triple-negative breast cancer biology at the level of somatic mutations, which are not inherited but acquired by cancer cells during disease development and progression.”
Study Methods and Rationale
Triple-negative breast cancer disproportionately affects African American women among all racial groups, yet these women are often underrepresented in genomic studies of triple-negative breast cancers.
The researchers conducted a genomic analysis of triple-negative breast cancers in African American women to determine if the mutational profile matches that of triple-negative breast cancers in other populations. They completed whole-exome and RNA sequencing of paired tumor and normal samples from 462 African American women with triple-negative breast cancer.
Key Study Findings
The researchers found that there was no evidence of associations of mutational features with African ancestry among the African American women with triple-negative breast cancer analyzed in the study, which went against the theory of racial differences in triple-negative breast cancer biology on the basis of somatic mutations.
Yao et al found the presence of TP53 mutations in 95% of the women analyzed in the study, which was more than previously realized. Additionally, they identified a low frequency of PIK3CA mutations and mutational signature-based subtypes with etiologic and prognostic significance.
They found that one pathway of breast cancer development was related to genetic predisposition and faulty DNA damage repair found in younger patients, whereas another avenue for development was found in older patients in pathways related to aging and obesity.
“We tend to link triple-negative breast cancer 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 triple-negative breast cancer as well,” Dr. Yao said.
This allowed the researchers to separate tumors into subtypes by patterns of aging and homologous recombination deficiency mutational signatures. Each subtype was associated with different demographic and prognostic features.
The genomic findings also offered possibilities of more effective treatment approaches for African American women with triple-negative breast cancer, including immunotherapy or targeted therapy for a majority of the analyzed patients.
Disclosure: 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. For full disclosures of the study authors, visit nature.com.
