Body mass index and breast cancer risk among postmenopausal women with and without cardiometabolic diseases: Findings from two prospective cohort studies in Europe

Abstract Background Adiposity, measured by body mass index (BMI), is a known risk factor for postmenopausal breast cancer. However, whether the association of BMI with breast cancer risk differs among women with and without cardiovascular diseases (CVDs) or type 2 diabetes (T2D) is uncertain. Methods This study used individual participant data from the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank (UKB) that included 168,547 postmenopausal women who were free of cancer, T2D, and CVD at recruitment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with multivariable‐adjusted Cox regression for associations between BMI and incident breast cancer by T2D and CVD status. Incidence rates per 1000 person‐years and rate differences between observed and expected joint associations of adiposity and CVD or T2D for breast cancer were estimated. Study‐specific estimates were meta‐analyzed. Results After a median follow‐up of 10.7 years in EPIC and 10.9 years in UKB, 6793 postmenopausal women developed breast cancer. In the meta‐analysis of both cohorts, BMI (per 1‐SD increment, 5 kg/m 2 ) was more strongly associated with breast cancer risk in women with CVD (HR, 1.31; 95% CI, 1.16 to 1.47) than in women without CVD (HR, 1.13; 95% CI, 1.11 to 1.16) ( p interaction = .02). T2D did not modify breast cancer risk ( p interaction = .33). The meta‐analyzed joint association of overweight or obesity (BMI, ≥25 kg/m 2 ) and CVD led to 1.53 (95% CI, 0.35 to 2.71) more cases of breast cancer per 1000 person‐years than expected but no such joint association was observed with T2D. Conclusions Adiposity‐associated risk of breast cancer was substantially higher among women with CVD as compared to those without CVD.