ASSOCIATION OF METFORMIN WITH BREAST CANCER INCIDENCE AND MORTALITY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Background Preclinical data suggests that metformin may have anti-cancer effects to reduce breast cancer incidence and improve cancer prognosis. However, the current evidence in observational studies is inconclusive. A systematic review and meta-analysis was conducted to assess the effect of metformin on the incidence and mortality of breast cancer in diabetic patients.

Methods A comprehensive literature search was performed on Medline (Pubmed), EMBASE, and the Cochrane library from inception to November 2016 with no language restrictions. Outcomes were incidence of breast cancer and all-cause mortality. Risk of bias and overall quality of evidence was assessed using the Newcastle Ottawa Scale and GRADE respectively. A meta-analysis was performed using the most adjusted odds ratios (ORs) or hazard ratios (HRs) and 95% confidence intervals (95% CI) as effect measures.

Results A total of 12 observational studies were included for breast cancer incidence and 11 studies for all-cause mortality. No significant association was found between metformin exposure and incidence of breast cancer (OR: 0.93, 95% CI: 0.85-1.03, I2 = 35%). A 45% risk reduction was observed for all-cause mortality (HR: 0.55, 95%CI: 0.44-0.70, I2=81%). Presence of publication bias is strongly suspected for both outcomes.

Conclusion The use of metformin in standard cancer therapy may improve overall survival of diabetic patients with breast cancer. No effect of metformin on the incidence of breast cancer was observed. Interpretation of results is limited by the observational nature of the studies and methodological biases. Clinical trials are warranted to determine the role of metformin in breast cancer risk reduction and prognosis.