The effect of metformin on biomarkers and survivals for breast cancer- a systematic review and meta-analysis of randomized clinical trials.

Observational studies show a beneficial effect of adjuvant metformin therapy on breast cancer survivals, but data from randomized clinical trials are lacking. This study systematically evaluated the evidence from randomized clinical trials currently available. Ten studies were retrieved, comprising 1520 breast cancer patients. Metformin therapy reduced the levels of insulin and HOMA-IR, sex hormones and sex hormone-binding globulin, Ki67, caspase-3, p-Akt, obesity, hs-CRP, blood glucose and lipid profile. Two studies reported conflicting results on survival outcomes. The overall survival was nonsignificantly better in the metformin arm than the control arm (pooled rate ratio 0.89, 95% confidence interval 0.68-1.18, P = 0.43). The progression-free survival was not different between the arms (pooled rate ratio 0.96, 95% confidence interval 0.86-1.06, P = 0.39). These findings provide in vivo evidence in human, supporting an antitumor effect of metformin on breast cancer. Further clinical trials with larger sample size are warranted.