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

Hamam NG, Samir M, Almosilhy NA, Whdan MM, Mohamed OA, Helal MM

Clinical breast cancer, 2026

582 participants

Abstract

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,…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 582 participants or records.

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