Site Editor
William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Friday, April 21, 2023
Rachel Martini, PhD, of Weill Cornell Medicine, New York, and colleagues presented their findings on the tumor microenvironment of triple-negative breast cancer (TNBC) at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract NG03). There is a higher mortality rate for triple-negative breast cancer among African American women compared with White/European American women, and the frequency of triple-negative breast cancer diagnoses seems to be significantly higher among African American women. The researchers sought to identify African ancestry–specific factors driving these differences in tumor etiology, and their findings may ultimately lead to targeted therapeutic opportunities for this underserved population.
The researchers leveraged multiomics approaches, identifying unique African ancestry–specific gene-expression profiles and enrichments using transcriptomic approaches and determining mutational profiles and signatures enriched among women of African ancestry with triple-negative breast cancer with whole-genome sequencing. They identified an African ancestry–associated gene signature comprised of 613 genes, showing enrichment in immune cell trafficking pathways. The gene signature revealed significant increases in tumor-associated leukocyte proportions among African American and Ghanaian women, specifically B- and T-cell populations. Validation cohorts showed significant increases in T-cell infiltration into triple-negative breast cancer tumors of African-ancestry women.
Whole-genome sequencing analysis was completed on a cohort of patients with triple-negative breast cancer and hormone receptor (HR)-positive breast cancer. The analysis of top mutated genes revealed a significantly high frequency of TP53 mutations in triple-negative breast cancer (82%) as compared with HR-positive cases (35%), with primarily missense and nonsense mutations in the P53 DNA-binding domain. The researchers also reported the rs2363956 germline variant of the ANKLE1 gene as a potential triple-negative breast cancer protective allele among African American women, where ANKLE1 is reported to play a role in DNA repair pathways.
Disclosure: The study authors reported no conflicts of interest.
JNCCN Spotlights
Resources
For your Patients
