Proceedings of the 2013 annual meeting of the Netherlands Epidemiology Society
Volume 1 Issue S1 Abstract 27
P.J.H.L. Peeters, Utrecht University, Utrecht, the Netherlands
M.T. Bazelier, Utrecht University, Utrecht, the Netherlands
P. Vestergaard, Aalborg University, Aalborg, Denmark
H.G.M. Leufkens, Utrecht University, Utrecht, the Netherlands
M.K. Schmidt, Netherlands Cancer Institute, Amsterdam, the Netherlands
F. de Vries, UMC Utrecht & UMC Maastricht, the Netherlands; University of Southhampton, UK
M.L. De Bruin, Utrecht University, Utrecht, the Netherlands
Breast cancer patients with diabetes mellitus have a higher mortality risk compared with their nondiabetic counterparts. Preclinical studies have suggested that metformin reduces growth of breast cancer cells. However, results from clinical trials and observational studies thus far remain inconclusive with regard to the clinical relevance of the effect. Objectives: We conducted a cohort study within the Danish national health registries to determine whether breast cancer patients who received metformin had a lower risk of all-cause and breast-cancer specific mortality as compared with women who received other oral antidiabetic drugs.
We identified 1058 adult female patients with breast cancer and prevalent type 2 diabetes. Patients were followed from the moment of breast cancer diagnosis onwards. Women with prior cancer or insulin use were excluded. During follow-up, patients were censored at the time of a first recorded insulin prescription. We performed time-dependent multivariate Cox proportional hazards analyses to assess all-cause and breast cancer-specific mortality risks associated with metformin use, adjusted for age, comorbidity, and comedication. In a secondary analysis, use of metformin was stratified according to the cumulative number of prescriptions.
During a total follow-up of 2971 person-years 349 women died (152 cases of breast cancer). Compared with nonusers, metformin use was associated with a significant reduction in overall mortality (HR 0.74 [0.57-0.95]). For breast cancer-specific mortality, a non-significant risk reduction (HR 0.85 [0.58-1.26]) was observed. Differentiation according to the cumulative number of prescriptions showed a noticeable fluctuation in risk, ranging from increased mortality risk in the lowest exposure categories to significant protective effects in the categories with highest cumulative use. Unexpectedly, risk of both overall and breast cancer-specific mortality were increased in the first 12 months after discontinuation of metformin.
Our findings suggest that long-term metformin use may have a beneficial effect on survival in diabetic patients with breast cancer. These results should be interpreted with caution due to the limitations of our study.
Published: 06 Jun, 2013