Genomic Contributions to Breast Cancer Disparities

Dr. Tanya Keenan, M.D.

Dr. Tanya Keenan, M.D.

Multiple studies have consistently shown that African American patients with cancer have worse outcomes than their Caucasian counterparts. While social determinants of health play a critical role, the influence of tumor genetic differences has been less clear. As technology advancements, such as those employed by TCGA, allow for rapid and affordable interrogation of the human genome, scientists can more easily evaluate the impact of tumor genetic patterns on disparities. Uncovering these genetic drivers may lead to the discovery of specific therapeutic targets and improved medical treatments that could contribute to alleviating cancer outcome disparities.

As current and future breast oncologists, my colleagues and I were drawn to the 40% higher breast cancer mortality in African American women compared to white women. To investigate potential genetic contributions to this disparity, we conducted a study linking race and breast cancer recurrence to TCGA data on tumor genomic profiles, including somatic mutations, genomic diversity, and gene expression.

We found that African American women had a significantly higher prevalence of TP53 mutations, intratumor genetic heterogeneity, and basal tumor subtypes, all of which correlate with more aggressive tumor biology. Adjusting for these genomic factors decreased the observed higher risk of tumor recurrence in African Americans compared to Caucasians, suggesting that differences in tumor genomic profile contribute, at least partly, to the racial disparities in breast cancer outcomes.

Our work would not have been possible without the rich genetic data generously shared by TCGA. The racially diverse group of participants contributing to TCGA promotes investigation of cancer genetic differences by race. By connecting genomic data to clinical and outcome data, TCGA helped my team to advance our understanding of the impact of genetic variation on cancer outcome disparities.

However, our study is only the beginning of what needs to be a much larger movement toward inclusion in breast cancer research. Our results underscore the critical need to involve higher numbers of African American patients in precision medicine research, and additional research is needed to confirm these findings and elucidate why the observed genetic differences lead to worse clinical outcomes. Ultimately, by understanding the genetics of subtypes of breast cancer that disproportionately affect African Americans and developing novel targeted therapies, we may be able to reduce racial disparities in breast cancer outcomes.

Read more in Dr. Keenan's study, Comparison of the Genomic Landscape Between Primary Breast Cancer in African American Versus White Women and the Association of Racial Differences With Tumor Recurrence