Racial Disparity in Quadruple Negative Breast Cancer: Aggressive Biology and Potential Therapeutic Targeting and Prevention

SIMPLE SUMMARY: Quadruple negative breast cancer (QNBC), a subgroup of triple negative BC, has emerged as a highly aggressive BC subtype that disproportionately afflicts and impacts Black/African-American (AA) women. In this article, we review molecular distinctions in Black/AA and White/European-American (EA) QNBC biology as well as address potential non-genetic risk factors that could be underlying this racially disparate burden. We aim to provide deeper insight and provide a framework for novel discovery of actionable therapeutic targets and identify lifestyle changes to improve outcomes for Black/AA QNBC patients. ABSTRACT: Black/African-American (AA) women, relative to their White/European-American (EA) counterparts, experience disproportionately high breast cancer mortality. Central to this survival disparity, Black/AA women have an unequal burden of aggressive breast cancer subtypes, such as triple-negative breast cancer (ER/PR-, HER2-wild type; TNBC). While TNBC has been well characterized, recent studies have identified a highly aggressive androgen receptor (AR)-negative subtype of TNBC, quadruple-negative breast cancer (ER/PR-, HER2-wildtype, AR-; QNBC). Similar to TNBC, QNBC disproportionately impacts Black/AA women and likely plays an important role in the breast cancer survival disparities experienced by Black/AA women. Here, we discuss the racial disparities of QNBC and molecular signaling pathways that may contribute to the aggressive biology of QNBC in Black/AA women. Our immediate goal is to spotlight potential prevention and therapeutic targets for Black/AA QNBC; ultimately our goal is to provide greater insight into reducing the breast cancer survival burden experienced by Black/AA women.