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

Abstract

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.

Racial Disparities and Survival Outcomes in Breast Cancer

“…This is notable because in the US female population, the percentage of White women (59.2%) was less than 5 times larger than that of Black women (13.9%) in 2018 . These facts mean that the incidence of ER-positive breast cancer was twice as high among Black patients compared to their White counterparts in this study, which contradicts a previous report by Gloeckler Ries et al suggesting a lower incidence of breast cancer in the Black population. This discrepancy may be due to selection bias, as the 21-gene screening test is expensive, with an approximate price of $4000, leading financially disadvantaged patients to opt against receiving the test.…”

Racial Disparities and Survival Outcomes in Breast Cancer—Reply

“…In Reply We thank Shigeta et al for their comments on our mediation analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Oncotype DX database that examined the associations of social determinants of health and tumor biology with the racial survival disparity between Black and White women with estrogen receptorpositive, axillary lymph node-negative, invasive breast cancer in the US. 1 We agree with Shigeta et al that an important finding from our study, in addition to showing that social determinants of health and aggressive tumor biology (as reflected by the 21-gene recurrence score [RS], tumor grade, and lack of progesterone receptor expression) were equally associated with worse survival for Black women, is that over half of the disparity cannot be accounted for by variables available in the SEER database. This underscores the need for additional research on the topic with more comprehensive measures of treatment-associated variables, social context, environmental exposures, personal characteristics, and genetic factors.…”

“…Shigeta et al correctly note that the proportion of Black women in our study (9.4%) 1 was lower than the overall proportion of Black individuals in the US population (12.6%) according to 2020 census data. 2 There are several potential explanations for this, including a disproportionately lower number of Black women with early-stage tumors 3 and inequitable ordering of the 21-gene RS assay among oncologists, 4 which were eligibility criteria for study inclusion.…”

“…Our study did not examine breast cancer incidence. 1 Several inclusion and exclusion criteria were applied to the SEER data set to generate the analytic cohort that was used for this study (eg, we excluded women without a 21-gene RS available, those with tumors that stained negative for ER or positive/borderline for ERBB2, those with axillary lymph node metastases, or those who did not have follow-up data available). For that reason, no conclusions can be drawn from our analysis regarding racial differences in breast cancer incidence.…”

“…Finally, Shigeta et al concur with our statement that social stressors, such as structural racism, racial animus, and discrimination, may be associated with tumor biology in Black women. 1 They make the interesting suggestion of examining temporal trends by comparing racial differences prior to and after the racial justice protests that were reignited around the world following the death of George Floyd in 2020 in order to identify the associations of race-related social stressors. We agree that this could be an informative analysis, but unfortunately, the SEER Oncotype DX database used for this study only included women diagnosed through 2015.…”