Use of Metformin and Survival of Diabetic Women with Breast Cancer
Paul JHL Peeters, Marloes T. Bazelier, Peter Vestergaard, Hubert G.M. Leufkens, Marjanka K. Schmidt, Frank de Vries and Marie L. De Bruin
Affiliation: Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands
Objective: This study was set out to determine whether metformin use influences survival in breast cancer
patients treated with antidiabetic drugs as compared to non-users.
Research Design and Methods: We used data from the Danish national registries (1996-2008) to identify adult female
patients diagnosed with breast cancer who were prescribed antidiabetic medication. We performed multivariate Coxproportional
hazard regression to assess all-cause and breast cancer-specific mortality risks associated with metformin
exposure. In a secondary analysis, we stratified use of metformin according to the cumulative number of prescriptions.
Results: Of the 1058 breast cancer patients 349 died during follow-up, with breast cancer listed as the primary cause of
death for 152 cases. Compared to non-use, current metformin treatment was associated with a significant reduction in
overall mortality (adjusted HR 0.74, 95% CI, 0.58-0.96). For breast cancer-specific mortality, a non-significant risk
reduction (adjusted HR 0.88, 95% CI, 0.59-1.29) was observed, which became significant after stratification according to
cumulative number of prescriptions. An increased risk of both overall and breast cancer-specific mortality was observed
in the first 12 months after discontinuation of metformin.
Conclusions: We observed a nonsignificant reduction in breast cancer-specific mortality associated with metformin
exposure among breast cancer patients treated with antidiabetic drugs. However, our findings suggest that long-term
metformin use may have a beneficial effect on survival in patients with breast cancer. Further confirmation of these
findings is needed.
Keywords: Breast cancer, metformin, mortality, survival, type 2 diabetes mellitus.
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