Type 2 Diabetes, but Not Insulin (Analog) Treatment, Is Associated With More Advanced Stages of Breast Cancer: A National Linkage of Cancer and Pharmacy Registries

OBJECTIVE To investigate whether women with type 2 diabetes (T2D) develop a more advanced stage of breast cancer and whether treatment with insulin (analogs) is associated with specific breast cancer characteristics. RESEARCH DESIGN AND METHODS For this nested case-control study, women with breast cancer diagnosed in 2002–2014 were selected from the linked Netherlands Cancer Registry–PHARMO Database Network (N = 33,377). T2D was defined as receiving two or more dispensings of noninsulin blood glucose–lowering drugs prior to breast cancer diagnosis. Women with T2D were matched to women without diabetes. Among women with T2D, insulin users and nonusers were compared. Multivariable ordinal logistic regression was used to investigate the association between T2D/insulin and breast cancer characteristics, including TNM classification (tumor size, lymph node status, metastasis), morphology, grade, estrogen receptor and progesterone receptor (PR), human epidermal growth factor receptor 2, and molecular subtype. RESULTS Women with T2D (n = 1,567) were more often diagnosed with a more advanced tumor stage (odds ratio 1.28 [95% CI 13–1.44]) and a higher grade (1.22 [1.08–1.39]) though less often with a PR-negative breast tumor (0.77 [0.67–0.89]) than women without diabetes (n = 6,267). No associations were found for the other breast cancer characteristics. Women with T2D using insulin (n = 388) were not diagnosed with different breast cancer characteristics compared with women with T2D not using insulin (n = 1,179). CONCLUSIONS Our study suggests that women with T2D are at increased risk to be diagnosed with a more aggressive type of breast cancer than women without diabetes. No evidence was found that the use of insulin (analogs) is associated with developing more advanced breast cancer tumors.