Abstract

Abstract Racial disparities in breast cancer outcome are most pronounced among women with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) disease. Several factors may contribute to this disparity, including biologic heterogeneity within the clinical HR+/HER2- subtype, and differences in access to treatment. In this study, we leverage the unique resources of the Carolina Breast Cancer Study Phase III (CBCS-III), a large prospective cohort study including tumor bio-specimens and detailed clinical annotation from black and white women with breast cancer, to examine potential contributors to racial disparities in recurrence of HR+/HER2- breast cancer. The CBCS-III cohort includes 2,998 women recruited between 2008 and 2013 by rapid case ascertainment from 44 counties in North Carolina, stratified by age (>50 versus <50) and race (black vs white). For this analysis, we included 1,629 women with stage I-III, HR+/HER2- clinical phenotype. We performed Cox proportional hazards regression to assess the effect of race on recurrence-free survival (RFS). Model 1 was minimally adjusted for age. Model 2 additionally adjusted for clinical factors likely to vary by race and to affect recurrence risk, including stage, grade, and the receipt of adjuvant chemotherapy. Finally, for patients who had specimens available (n=935), models were fit adjusting for clinical variables as well as PAM50 Risk of Recurrence score with both proliferation index and tumor size (ROR-PT) (Model 3) or molecular subtype dichotomized as Luminal A versus other (Model 4). With a median follow-up time of 5.5 years, 8.6% (118/1371) of whites and 14% (196/1403) among blacks had recurrence. After adjustment for age, black patients were at significantly higher risk for recurrence (HR=2.01, 95% CI 1.40-2.88), and this disparity was only partially attenuated by adjusting for baseline clinical factors (HR 1.62, 95% CI 1.11-2.36). Additional adjustment for molecular features by either ROR-PT score or molecular subtype further attenuated, but did not eliminate, the disparity in recurrence risk (HR=1.51, 95% CI 0.81,2.81 using ROR-PT and HR=1.44, 95% CI 0.77-2.69 using subtype category). Results are summarized in Table 1. Models of Recurrence Free Survival by Race (white = ref) HR95% CIModel 12.01(1.40, 2.88)Model 21.62(1.11, 2.36)Model 31.51(0.81, 2.81)Model 41.44(0.77, 2.69)Adjusted for: (1) age; (2)age, AJCC stage, grade, chemo; (3)ROR-PT, assay technique factor, and variables in Model 2; (4)PAM 50 subtype, assay technique factor, and variables in Model 2. In this recent population-based cohort, black women with HR+/HER2 negative disease remain twice as likely as their white counterparts to experience a recurrence within 5 years. Clinical features at disease presentation do not fully explain these outcome differences, while adjustment for biologic heterogeneity by either ROR-PT score or molecular subtype attenuates the observed disparity more than clinical features alone. There are likely residual factors not measured in this analysis, such as endocrine therapy under-use or other biologic differences, which may be targetable determinants of survival disparities. These hypotheses are being actively explored in CBCS-III. Citation Format: Reeder-Hayes KE, Sun X, Olshan A, Carey LA, Troester MA. Racial differences in recurrence of hormone receptor-Positive breast cancers in the Carolina breast cancer study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-13-05.

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