Association of Social Determinants and Tumor Biology With Racial Disparity in Survival From Early-Stage, Hormone-Dependent Breast Cancer

Abstract

Importance: Black 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.

Objective: To 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 participants: A 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.

Exposures: Census tract socioeconomic disadvantage, insurance status, tumor characteristics including the recurrence score, and treatment variables.

Main outcomes and measures: Death due to breast cancer.

Results: The 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 relevance: In 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.

Figure.. Proportion of the Racial Disparity in Death from ER-positive Breast Cancer Mediated by Social Determinants of Health, Tumor Features, and Treatment

Proportionate reduction of the disparity in the age-adjusted hazard of death from ER-positive, axillary node-negative breast cancer comparing Black versus White patients after controlling for specific domains that mediate the disparity. Domains include census tract socioeconomic index (SEI), health insurance status (Insurance), oncotype 21-gene recurrence score (RS), progesterone receptor status and tumor grade modeled together (tumor characteristics), tumor size, and treatment (chemotherapy and radiation initiation). Hazard ratios were estimated from discrete-time survival models adjusted for age. Two estimates of proportionate reduction are shown: those based on the reduction in the excess hazard ratio (blue circles), and those based on the change in rescaled coefficients before and after adjusting for the domain of mediating variables (orange circles). Cases diagnosed prior to 2007 were excluded from all analyses that include health insurance status as a variable in the model since SEER did not collect health insurance data prior to 2007. ^aAll estimates of the proportionate reduction in the Black vs White disparity with rescaled coefficients had a P < .001.