Addressing Racial Disparities in Quadruple-Negative Breast Cancer: Insights Into Aggressive Biology, Therapeutic Targets, and Prevention Strategies

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). TNBC is inherently more clinically aggressive than the other breast cancer subtypes as evidenced by the higher frequency of metastasis and recurrence within 5 years of diagnosis. 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). QNBCs are significantly more aggressive than AR-positive TNBCs. QNBC is increasingly recognized as an aggressive, hard-to-treat breast cancer subtype. 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, a discussion has been developed on the racial disparities of QNBC and molecular signaling pathways that may contribute to the aggressive biology of QNBC in Black/AA women. This study intends to spotlight potential prevention and therapeutic targets for Black/AA QNBC; ultimately the goal of this study is to provide greater insight into reducing the breast cancer survival burden experienced by Black/AA women. Non-genetic risk factors include lifestyle, socioeconomic status, access to quality oncological care, reproductive factors, anthropometrics, and comorbidities have long been reported to contribute to the gap in survival rates between Black/AA and White/EA women with breast cancer. The Potential Role of Non-Genetic Risk Factors in the Racially Disparate Burden in QNBC is also discussed here. Addressing the racial disparity in the highly aggressive breast cancer subtype, QNBC could significantly contribute to reducing the racially disparate burden of breast cancer.