Cardiometabolic Health and Risk of Breast Cancer Subtypes Among US Black Women

In the United States (US), cardiometabolic conditions and aggressive breast cancers are both more common among Black women than White women. Using data from 57,453 participants in the Black Women's Health Study (BWHS), we prospectively evaluated associations of body mass index (BMI), Type 2 diabetes, hypertension, and hypercholesterolemia with incidence of breast cancer. Pathology records were used to classify cases by estrogen receptor (ER) status and subtype (luminal A-like, luminal B-like, HER2-overexpressed, and triple negative). We used competing risk Cox proportional hazards models to estimate hazard ratios (HR), adjusting for age, reproductive factors, and lifestyle factors. Among postmenopausal women, BMI ≥ 30 kg/m² (vs. < 25 kg/m²) was associated with increased risks of ER+ (HR = 1.35, 95% CI = 1.15-1.59) breast cancer and the luminal A-like subtype (HR = 1.54, 95% CI = 1.19-1.98). No other cardiometabolic factors were associated with breast cancer subtypes. Relative to those with no cardiometabolic factors, postmenopausal women with ≥ 3 cardiometabolic conditions had a 43% higher risk of ER+ cancer (95% CI = 1.04-1.97) and a 38% lower risk of ER- cancer (95% CI = 0.37-1.02; p-heterogeneity = 0.006). Analyses of all possible combinations of 2 or 3 factors resulted in HRs > 1.0 for analyses of ER+ breast cancer and HRs not significantly different from 1.0 for analyses of ER- breast cancer. There were no statistically significant findings among premenopausal women. In this large cohort of Black women, poorer cardiometabolic health was associated with higher ER+ and lower ER- breast cancer risk among postmenopausal women. These divergent associations support a role for metabolic-endocrine crosstalk in breast cancer etiology.