Metformin in Breast Cancer: Molecular Mechanisms, Preclinical Evidence and Clinical Implications
DOI:
https://doi.org/10.12775/JEHS.2025.86.66918Keywords
metformin, breast cancer, AMPK, mTOR, cancer therapy, chemotherapy, T2DMAbstract
Background: Metformin, a first-line therapy for type 2 diabetes mellitus, has recently attracted attention for its potential anticancer properties. Preclinical and clinical evidence suggests that it modulates cancer cell metabolism, proliferation and survival pathways, indicating its possible role as an adjunct therapeutic agent, particularly in breast cancer.
Aim: To summarize current knowledge on the mechanisms of action, preclinical outcomes and clinical implications of metformin use in breast cancer.
Material and methods: A comprehensive literature search was conducted in PubMed, Scopus, Web of Science and Google Scholar databases, including publications up to 2025. Eligible sources encompassed preclinical studies, clinical trials, observational data, meta-analyses and reviews addressing metformin in breast cancer.
Results: Metformin demonstrates multifaceted antitumor activity, including inhibition of cell proliferation, reduced angiogenesis, downregulation of the PI3K/AKT/mTOR pathway, depletion of cancer stem cell populations and improved chemotherapy response. Clinical benefits are most evident in patients with type 2 diabetes and HER2-positive tumors, although findings in the general population remain inconsistent.
Conclusions: Metformin appears to be a promising supportive therapy in selected breast cancer subgroups, particularly in metabolically burdened patients. Further high-quality randomized trials are essential to clarify its clinical relevance and identify biomarkers predicting treatment response.
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