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Black, white women display genomic differences in breast cancer tumors
Researchers identified genomic differences between breast cancer tumors of black and white women that could be associated with disparities in recurrence and survival rates.
Results showed black women had greater intratumor genetic heterogeneity and more basal gene-expression tumors than white women.
Tanya Keenan
“In addition to having a higher prevalence of triple-negative breast cancers than Caucasian women — something that has been documented in previous studies — we found that African American women with breast cancer had a significantly higher prevalence of the TP53 driver mutation, basal tumor subtype and greater genomic diversity within tumors, all of which suggest more aggressive tumor biology,” Tanya Keenan, MD, a resident at Massachusetts General Hospital Cancer Center, said in a press release. “The higher risk of tumor recurrence that we observed among African American women was reduced when controlling for those factors, suggesting that these genomic differences contribute, at least partly, to the known racial disparity in the survival of African American and Caucasian breast cancer patients.”
Keenan and colleagues retrospectively evaluated data from white and black women diagnosed with stage I to stage III breast cancer between 1988 and 2013. Researchers also evaluated data from primary tumors that were submitted to the Cancer Genome Atlas from 2010 to 2014.
The analysis included exome sequencing data from 663 white women and 105 black women and gene expression data from 711 white women and 159 black women.
A greater proportion of black women harbored TP53 mutations than white women (42.9% vs. 27.6%; P = .03), whereas fewer black women harbored PIK3CA mutations (20% vs. 33.9%; P = .008).
Genetic heterogeneity within the tumor was higher by 5.1 units (95% CI, 2.4-7.7) among blacks than whites overall and by 4.1 units (95% CI, 1.4-6.8) within triple-negative tumors.
Data from the prediction analysis of microarray method with a 50-gene set predictor (PAM50) indicated a greater proportion of blacks had basal cell tumors than whites (39% vs. 18.6%; P < .001) and fewer had PAM50 luminal A tumors (17% vs. 34.7%; P < .001).
In the triple-negative subtype, more black women had more basal-like 1 and mesenchymal stem-like tumors. Adjustments for age and stage indicated black women with triple-negative disease were more likely to have basal-like 1 (OR = 6.21; 95% CI, 1.53-25.25) and mesenchymal stem-like (OR = 4.38; 95% CKI, 1.01-18.97) tumors.
Overall, the risk for tumor recurrence was higher among blacks than whites (HR = 2.22; 95% CI, 1.05-4.67). However, Cox regression using propensity scores matched on age, HR-positive status, mutant-allele tumor heterogeneity algorithm, triple-negative breast cancer, TP43 and PIK3CA mutations, and PAM50 basal status demonstrated no difference in tumor recurrence between blacks and whites (HR = 1.39; 95% CI, 0.68-2.84).
The researchers wrote that the study may be limited by a lack of information on cause of death — which prevented an analysis of racial differences in breast cancer-specific mortality — as well as by the potential for selection bias and a short follow-up.
Aditya Bardia
Other limitations included a lack of information on sociodemographic factors, germline mutations and treatment variables.
“Our study adds important pieces to the puzzle of why African American women with breast cancer are less likely to survive,” Aditya Bardia, MBBS, MPH, attending physician at Massachusetts General Hospital Cancer Center and assistant professor of medicine at Harvard Medical School, said in the release. “If our findings are confirmed by additional studies, they may open the doors to the development of targeted therapies against the tumor subtypes more likely to affect African Americans and potentially help reduce racial disparities in breast cancer.” – by Anthony SanFilippo
Disclosure: Keenan reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.