Metformin as a Neoadjuvant to Chemotherapy in Locally Advanced and Metastatic Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
In brief
Metformin boosts overall pathological response to chemotherapy by about 30%
In a meta-analysis of eight randomized trials involving 582 women with locally advanced or metastatic breast cancer, adding metformin to standard chemotherapy increased the rate of any pathological response by roughly one-third without raising overall toxicity, though severe diarrhea was more common. The improvement also translated into more breast-conserving surgeries, but its impact on long-term survival remains unknown.
- Journal
- Clinical breast cancer (Q2)
- Published
- 17 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Nada G Hamam, Mahmoud Samir, Nereen A Almosilhy, Mohamad Mahmoud Whdan, Omar A Mohamed, Mohamed Mohsen Helal
- PMID
- 42566923
- DOI
- 10.1016/j.clbc.2026.07.017
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (top studies of the week, 9 August 2026).
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, 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.