Metformin as a Neoadjuvant to Chemotherapy in Locally Advanced and Metastatic Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Several clinical trials have investigated the potential role of metformin as an adjunct to chemotherapy. This meta-analysis aims to assess its efficacy and safety as an adjunct to chemotherapy based on the results of the available RCTs. A comprehensive search was conducted through 5 databases using relevant terms for breast cancer and metformin. PRISMA guidelines were followed. Screening and data extraction steps were performed independently by 2 authors. Meta-analysis was performed on RevMan. A random-effects model was used in case of significant heterogeneity; otherwise, a fixed-effects model was used. Eight studies were included in the systematic review with 582 patients. The overall pathological response rate was better in the metformin (M-Chemo) group compared to the chemotherapy alone (Chemo) group (RR = 1.30, 95% CI [1.14, 1.50], P = .0002). Although the complete pathological response rate did not differ (RR = 1.291, 95% CI [0.977, 1.706], P = .073), the number of patients with no pathological response was significantly less in the M-Chemo group (RR = 0.44, 95% CI [0.20, 0.95], P = .04). Patients requiring breast conservative surgery after the treatment course were more in the M-Chemo group (RR = 1.52, 95% CI [1.15, 2.01], P = .003), whereas the number of patients planned for mastectomy did not differ (RR = 0.90, 95% CI [0.80, 1.02], P = .09). Adverse events were similar between groups, except for higher rates of grade 3 to 4 diarrhea in the M-Chemo group (RR = 7.09, 95% CI: 1.27-39.51, P = .03). Adding metformin to chemotherapy improves response without increasing adverse events and may promote breast-conserving surgery; further studies are needed to assess survival outcomes.