History of Gestational Diabetes Mellitus and Risk of Incident Invasive Breast Cancer among Parous Women in the Nurses' Health Study II Prospective Cohort

Abstract Background: Type II diabetes is associated with breast cancer in epidemiologic studies. Pregnancy also modifies breast cancer risk. We hypothesized that women with a history of gestational diabetes mellitus (GDM), which shares pathogenesis and risk factors with type II diabetes, would have greater invasive breast cancer risk than parous women without a history of GDM. Methods: We conducted a prospective analysis among parous women in the Nurses' Health Study II, with mean age 35 years in 1989. Multivariate Cox proportional hazards models were used to compare risks of incident invasive breast cancer in women with and without a history of GDM. Results: Among 86,972 women studied, 5,188 women reported a history of GDM and 2,377 developed invasive breast cancer (100 with history of GDM, 2,277 without GDM) over 22 years of prospective follow-up. History of GDM was inversely associated with incident invasive breast cancer [HR, 0.68; 95% confidence interval (CI), 0.55–0.84; P = 0.0004], compared with no history of GDM, after adjustment for body mass index, reproductive history, and other breast cancer risk factors. Findings were similar by menopausal status, although observed person-time was predominantly premenopausal (premenopausal: HR, 0.73; 95% CI, 0.56–0.96; P = 0.03; postmenopausal: HR, 0.63; 95% CI, 0.43–0.92; P = 0.02). Restricting to women undergoing mammography screening modestly attenuated the relationship (HR, 0.74; 95% CI, 0.57–0.96; P = 0.02). Conclusions: Among a large cohort of U.S. women, history of GDM was not associated with an elevated risk of subsequent invasive breast cancer. Impact: Our findings highlight the need to further investigate GDM's role in breast cancer development. Cancer Epidemiol Biomarkers Prev; 26(3); 321–7. ©2016 AACR.