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

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.

SUBMITTER: Jinna N

PROVIDER: S-EPMC9497140 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Jinna Nikita N Jovanovic-Talisman Tijana T LaBarge Mark M Natarajan Rama R Kittles Rick R Sistrunk Christopher C Rida Padmashree P Seewaldt Victoria L VL

Cancers 20220916 18

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 bre ...[more]

PMID: 36139643

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Project description:ImportanceBlack women with hormone receptor-positive breast cancer experience the greatest racial disparity in survival of all breast cancer subtypes. The relative contributions of social determinants of health and tumor biology to this disparity are uncertain.ObjectiveTo determine the proportion of the Black-White disparity in breast cancer survival from estrogen receptor (ER)-positive, axillary node-negative breast cancer that is associated with adverse social determinants and high-risk tumor biology.Design, setting, and participantsA retrospective mediation analysis of factors associated with the racial disparity in breast cancer death for cases diagnosed between 2004 and 2015 with follow-up through 2016 was carried out using the Surveillance, Epidemiology, and End Results (SEER) Oncotype registry. The study included women in the SEER-18 registry who were aged 18 years or older at diagnosis of a first primary invasive breast cancer tumor that was axillary node-negative and ER-positive, who were Black (Black), non-Hispanic White (White), and for whom the 21-gene breast recurrence score was available. Data analysis took place between March 4, 2021, and November 15, 2022.ExposuresCensus tract socioeconomic disadvantage, insurance status, tumor characteristics including the recurrence score, and treatment variables.Main outcomes and measuresDeath due to breast cancer.ResultsThe analysis with 60 137 women (mean [IQR] age 58.1 [50-66] years) included 5648 (9.4%) Black women and 54 489 (90.6%) White women. With a median (IQR) follow-up time of 56 (32-86) months, the age-adjusted hazard ratio (HR) for breast cancer death among Black compared with White women was 1.82 (95% CI, 1.51-2.20). Neighborhood disadvantage and insurance status together mediated 19% of the disparity (mediated HR, 1.62; 95% CI, 1.31-2.00; P < .001) and tumor biological characteristics mediated 20% (mediated HR, 1.56; 95% CI, 1.28-1.90; P < .001). A fully adjusted model that included all covariates accounted for 44% of the racial disparity (mediated HR, 1.38; 95% CI, 1.11-1.71; P < .001). Neighborhood disadvantage mediated 8% of the racial difference in the probability of a high-risk recurrence score (P = .02).Conclusions and relevanceIn this study, racial differences in social determinants of health and indicators of aggressive tumor biology including a genomic biomarker were equally associated with the survival disparity in early-stage, ER-positive breast cancer among US women. Future research should examine more comprehensive measures of socioecological disadvantage, molecular mechanisms underlying aggressive tumor biology among Black women, and the role of ancestry-related genetic variants.

Dataset Information

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

Publications

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

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