Metformin and Incident Breast Cancer among Diabetic Women: A Population-Based Case-Control Study in Denmark

Background: Preliminary evidence suggests that metformin may decrease breast cancer risk by decreasing insulin levels and reducing cell proliferation. We evaluated the effect of metformin medication on the risk of incident breast cancer among peri- and postmenopausal women. Methods: We used Danish medical registries to conduct a nested case-control study among type 2 diabetic women 50 years or older who resided in northern Denmark from 1989 to 2008 (n = 4,323). We identified 393 diabetic cases and used risk-set sampling to select 10 diabetic controls per case (n = 3,930) matched on county of residence. Odds ratios (OR) and 95% CIs were estimated by conditional logistic regression associating metformin use with breast cancer occurrence. Results: Ninety-six cases (24%) and 1,154 controls (29%) used metformin for at least 1-year duration. Cases were slightly older on average than controls, but they were similar in distribution for parity, use of hormone replacement therapy, and history of diabetes complications. Metformin users were less likely with a diagnosis of breast cancer (OR = 0.77; 95% CI = 0.61-0.99) than nonmetformin users. Adjustment for diabetes complications, clinically diagnosed obesity, and important predictors of breast cancer did not substantially alter the association (OR = 0.81; 95% CI = 0.63-0.96). Conclusion: Our results suggest that metformin may protect against breast cancer in type 2 diabetic peri-or postmenopausal women. Impact: This study supports the growing evidence of a role for metformin in breast cancer chemoprevention. Cancer Epidemiol Biomarkers Prev; 20(1); 101-11. (C) 2011 AACR.