NEW YORK (GenomeWeb) – Findings from a new multi-institutional study have revealed new genomic patterns that contribute to higher mortality among black women with breast cancer than white women with similar tumors.
The results could lead to more personalized risk assessment for women of African ancestry, hasten development of novel diagnostic approaches, and inform more effective treatment, the study's authors noted.
Though black and white women have the same likelihood of developing breast cancer, black women are 42 percent more likely to die from the disease. Social and environmental disparities are known to contribute to this "mortality gap," but genomic factors are also presumably at work.
Published today in JAMA Oncology, the new study was designed to begin to unravel germline genetic variations and tumor biological differences between black and white women with breast cancer.
"People have long associated breast cancer mortality in black women with poverty, or stress, or lack of access to care, but our results show that much of the increased risk for black women can be attributed to tumor biological differences, which are probably genetically determined," University of Chicago professor and corresponding author Olufunmilayo Olopade said in a statement.
The study used genomic data collected as part of The Cancer Genome Atlas (TCGA) from 930 women, 154 of which were of predominantly African ancestry and 776 of which were of predominately European ancestry.
Though other studies have also investigated this question, the number of black women included in the new analysis was much higher and the outcome data more comprehensive, the authors argued.
Investigators combed the dataset looking for racial differences in germline variations, somatic mutations, molecular subtypes, and corresponding clinical data points like survival time. They also studied gene expression, protein expression, and DNA methylation patterns in patients for whom this additional data was available.
Amongst the findings, researchers reported that most somatic driver mutations didn't appear to differ significantly between black and white women. Black women did have more TP53 mutations and fewer PIK3CA mutations than white women, but these and many other molecular differences could be explained by differences in the frequencies of different subtypes of cancer between the two groups.
Beyond somatic mutations, the investigators also found 16 DNA methylation probes, four DNA copy number segments, one protein, and 142 genes that were differentially expressed between the two groups.
From these 142 genes, the researchers were able to glean an expression signature distinguishing breast tumor samples from blacks and whites with high specificity.
For one gene in particular, CRYBB2, expression was higher in black patients than in white patients consistently within each breast cancer subtype. Other studies have also determined that CRYBB2 expression is higher in normal breast tissue from black patients and in prostate cancer and colorectal cancer from black Americans compared with white Americans, suggesting that CRYBB2 is likely a true race-specific gene, the authors noted.
The study also confirmed some known disparities, including that black patients are typically diagnosed at a younger age and are more likely to develop aggressive breast-cancer subtypes such as basal-like or triple-negative cancers.
But with their comprehensive genetic data, the researchers were also able to link these differences in likelihood to underlying germline genetic differences.
Overall, they calculated that germline mutations appear to be responsible for up to 40 percent of the observed subtype frequency differences.
Though interesting, the findings are only a first step, the authors wrote, and underscore the need for larger genetic epidemiological studies to identify other factors that contribute to these frequency differences in breast cancer subtypes among black women versus other groups.
"As we learn more about these genetic variations, we can combine that information with clinical data to stratify risk and better predict recurrences — especially for highly treatable cancers — and develop interventions to improve treatment outcomes," Olopade said.
"Understanding the basic, underlying genetic differences between black and white women, the higher risk scores and the increased risk of recurrence should lead us to alternative treatment strategies," added co-author and University of North Carolina professor Charles Perou.