Metformin May Block the Way Breast Cancer Metastasis: A Meta-analysis and Mechanism Review

Abstract

Background Metformin, which is cheap and easy to get, is a first-line anti-hyperglycemia drug. Recently, its anti-tumor effect has been revealed. Here we performed a meta-analysis to summarize previous studies and a narrative review to gather the mechanisms involved in the potential relationship. Methods We searched related articles in database of Pubmed, EMbase, Web of science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), the Wanfang and Sinomed and obtained 8 clinic trials that investigated the connection between metformin and breast cancer metastasis, containing 2 randomized controlled trials (RCTs) and 6 retrospective cohort studies. We evaluated each retrospective cohort study by Newcastle-Ottawa Scale (NOS), while RCT by Chcorane Risk of Bias tool. Pooled hazard ratios (HRs), risk ratios (RRs) and we calculated associated 95% confidence intervals (CIs) with a random-effect, generic inverse variance method. We also collected the possible mechanisms of cancer metastasis inhibition from metformin. Results A total of 8 studies containing 13919 breast cancer patients without distant metastasis before they got anticancer treatment. The result showed that adjuvant metformin in treatment of local breast cancer facilitated to suppress metastasis (HR = 0.69, 95% CI = 0.57–0.82, p < 0.0001, I2 = 0%), and the result was consistent with the subgroup of breast cancer patients with type 2 diabetes mellitus (T2DM) (HR = 0.68, 95% CI = 0.57–0.82, p < 0.0001, I2 = 0%). Conclusion The meta-analysis suggested metformin might repress the metastasis and be benefit to distant metastasis-free survival (DMFS) when added to systemic breast cancer therapy, supporting anti-tumor effects of metformin on breast cancer.