Diabetes After Hormone Therapy in Breast Cancer Survivors: A Case-Cohort Study

Purpose Breast cancer treatments have been associated with an increased risk of multiple health-related adverse outcomes, but the relationship with diabetes remains unclear. This study investigated the association between hormone therapy and diabetes risk in breast cancer survivors. Patients and Methods We performed a case-cohort study of 2,246 female survivors recruited from the Leumit health care fund who were diagnosed with primary nonmetastatic invasive breast cancer in 2002 through 2012. A 20% random subcohort was sampled at baseline, and all diabetes cases were identified. Adjusted hazard ratios (HRs) with 95% CIs were estimated by weighted Cox proportional hazards regression models. Results Of 2,246 breast cancer survivors, 324 developed diabetes over a mean follow-up of 5.9 years. The crude cumulative incidence of diabetes that accounted for death as a competing risk was 20.9% (95% CI, 18.3% to 23.7%). In multivariable-adjusted models, hormone therapy was associated with increased diabetes risk (HR, 2.40; 95% CI, 1.26 to 4.55; P = .008). The hazard for tamoxifen use (HR, 2.25; 95% CI, 1.19 to 4.26; P = .013) was less pronounced than the use of aromatase inhibitors (HR, 4.27, 95% CI, 1.42 to 12.84; P = .010). Conclusion Active hormone therapy is a significant risk factor of diabetes among breast cancer survivors. Although cessation of treatment is not recommended because the survival benefits of hormone therapy outweigh the risks, preventive strategies aimed at lifestyle modifications may minimize the risk.