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Genetic Differences and BC Survival in Blacks and Whites
JAMA Oncology; ePub 2017 May 4; Huo, Hu, et al
There are genetic differences between blacks and whites that appear to contribute to substantial differences in breast cancer survival outcomes between the 2 groups, according to a study involving 930 individuals.
Investigators used breast tumor and matched normal tissue sample data to evaluate breast cancer–free interval, tumor molecular features, and genetic variants in blacks (n=154) and whites (n=776) with invasive breast cancer. Among the results:
- Blacks were more likely than whites to experience poor breast cancer-free interval.
- They were also nearly 4 times more likely to have basal-like subtype, and more than twice as likely to have human epidermal growth factor receptor 2-enriched subtype.
- Blacks had more TP53 mutations and fewer PIK3CA mutations.
- Molecularly, 16 DNA methylation probes, 4 DNA copy number segments, 1 protein, and 142 genes were found to be differentially expressed.
- Both estrogen receptor-positive and negative polygenic risk scores were higher in blacks.
Huo D, Hu H, Rhie S, et al. Comparison of breast cancer molecular features and survival by African and European ancestry in The Cancer Genome Atlas. [Published online ahead of print May 4, 2017]. JAMA Oncology. doi:10.1001/jamaoncol.2017.0595.
This study takes a novel approach to increasing our understanding of the breast cancer racial survival disparity. Analysis by DeSantis et al, cited an incidence rate of breast cancer at 135 per 100,000 women for both Caucasian and African American women in 2012.1 However, the mortality gap has continued to increase, with a death rate 42% higher in African American than in Caucasian women. In this ancestry-based comprehensive analysis of multiple platforms of genomic and proteomic data from the Cancer Genome Atlas, significant molecular differences were found between invasive breast cancers from genomically defined black and white patients. These differences, adjusted for subtype, included gene expression, protein, copy number, and DNA methylation. The authors estimated that more than 40% of the variation in intrinsic breast cancer subtype can be explained by inherited germline variants. Black patients had a higher likelihood of basal-like and human epidermal growth factor receptor 2-enriched breast cancer subtypes and were less likely to have luminal A subtype than white patients. The authors’ analysis also showed black patients had a higher risk of recurrence, particularly for basal-like cancers. This study calls for further investigation of genetic factors that contribute to the development of distinct breast cancer subtypes. With this knowledge, we can work to close the survival gap by better understanding how these genetic factors influence response to therapy. –Bobby Daly, MD, MBA