Metformin Use Is Associated With Better Survival of Breast Cancer Patients With Diabetes: A Meta-Analysis

Abstract

Background: Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pathologic complete response rate than do diabetic patients not receiving metformin, but findings on salvage treatment have been inconsistent. We performed a meta-analysis to assess the effect of adding metformin to standard therapy on the prognosis of breast cancer patients with diabetes.

Methods: We searched PubMed, Embase, Web of Science (Thomson Scientific), China Knowledge Resource Integrated Database, VIP journal integration platform, and Chinese BioMedical Literature Database from inception to January 10, 2015, without language restrictions, including references related to metformin, breast cancer, and prognosis. We performed the meta-analysis using a random-effects model, with hazard ratios (HRs) and 95% confidence intervals (95% CIs) as effect measures.

Results: A total of 11 studies consisting of 5,464 breast cancer patients with diabetes were included, comprising 2,760 patients who had received metformin and 2,704 patients who had not. The meta-analysis showed that metformin was associated with better overall survival times (HR: 0.53; 95% CI: 0.39-0.71) and cancer-specific survival times (HR: 0.89; 95% CI: 0.79-1.00). Subgroup analysis revealed that metformin improved the overall survival by 65% after adjusting for hormone receptor expression (HR: 0.35; 95% CI: 0.15-0.84). Taking metformin after the diagnosis of breast cancer was still associated with prolonged overall survival.

Conclusion: The use of metformin in standard cancer therapy might improve both overall and cancer-specific survivals of diabetic patients with breast cancer.

Implications for practice: Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pathologic complete response rate than diabetic patients not receiving metformin, but findings on salvage treatment have been inconsistent. The meta-analysis showed that metformin was associated with better overall survival times and cancer-specific survival times. Subgroup analysis revealed that metformin improved the overall survival by 65% after adjusting for hormone receptor expression. Taking metformin after the diagnosis of breast cancer was still associated with prolonged overall survival. The findings of this study highlight the potential usage of metformin in diabetic patients with breast cancer.

Keywords: Breast cancer; Diabetes mellitus; Meta-analysis; Metformin; Survival.

Figure 1.

Flow chart of study selection. Abbreviations: CBM, Chinese BioMedical Literature Database; CNKI, China Knowledge Resource Integrated Database; TS, Thomson Scientific; VIP, VIP journal integration platform.

Figure 2.

Meta-analysis and pooled hazard ratio of long-term, all-cause mortality in 11 studies (14 estimates) comparing breast cancer patients with and without metformin. Xiao (1), Xiao (2), and Xiao (3) indicate Luminal A, Luminal B (high Ki-67), and Luminal B (HER2+) subgroups, respectively. Xu (1) and Xu (2) indicate Vanderbilt and Mayo Clinic subgroups, respectively. Weights are from random effects analysis. Data markers are proportional to study sample sizes. Squares indicate relative risk in each study. The square size is proportional to the weight of the corresponding study in the meta-analysis; the lengths of the horizontal lines represent the 95% CI. The unshaded diamond indicates the pooled relative risk and 95% CI. Abbreviations: CI, confidence interval; HR, hazard ratio.