Impact of Genetic Ancestry on Treatment Toxicity and Racial Disparities in Breast Cancer

Purpose of Review Racial disparities in breast cancer are multifactorial and include inferior outcomes and increased rates of serious toxicity in African Americans. The purpose of this review is to evaluate the contribution of race, genetic ancestry, and genomic biomarkers to treatment toxicity and to demonstrate the impact of toxicity on racial disparities. Recent Findings Taxane-induced peripheral neuropathy (TIPN) and congestive heart failure (CHF) are potentially irreversible and life-altering toxicities of curative chemotherapy for breast cancer. Analysis of genetic ancestry, rather than self-reported race, in a large cooperative group adjuvant clinical trial discovered significantly higher rates of both TIPN and CHF in women of African descent compared with European Americans. Importantly, TIPN resulted in more dose reductions of chemotherapy in African Americans, which resulted in worse disease-free survival. Beyond race, significant individual variations in toxicity exist, which may be explained by validated genotypic predictors of TIPN and CHF, reviewed here. Summary Race, in particular genetic ancestry, impacts both tumor and host biology, contributing to toxicity that drives disparities in quality of life and survival. Translating these data into clinical decision-making will benefit from engagement of the African American community to perform clinical trials and develop datasets focused specifically in this population to validate biomarkers and best understand patient preferences.