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Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies
Karen A Corleto1,2, Jenna L Strandmo1, Erin D Giles2
1Department of Nutrition, Texas A&M University, College Station, TX 77843, USA.
Abstract:
Over the last several decades, a growing body of research has investigated the potential to repurpose the anti-diabetic drug metformin for breast cancer prevention and/or treatment. Observational studies in the early 2000s demonstrated that patients with diabetes taking metformin had decreased cancer risk, providing the first evidence supporting the potential role of metformin as an anti-cancer agent. Despite substantial efforts, two decades later, the exact mechanisms and clinical efficacy of metformin for breast cancer remain ambiguous. Here, we have summarized key findings from studies examining the effect of metformin on breast cancer across the translational spectrum including in vitro, in vivo, and human studies. Importantly, we discuss critical factors that may help explain the significant heterogeneity in study outcomes, highlighting how metformin dose, underlying metabolic health, menopausal status, tumor subtype, membrane transporter expression, diet, and other factors may play a role in modulating metformin's anti-cancer effects. We hope that these insights will help with interpreting data from completed studies, improve the design of future studies, and aid in the identification of patient subsets with breast cancer or at high risk for the disease who are most likely to benefit from metformin treatment.
Insights
Metformin, an anti-diabetic drug, shows potential for breast cancer treatment. However, its efficacy and mechanisms remain unclear, with varied outcomes influenced by patient and tumor factors.
Area of Science:
- Oncology
- Pharmacology
- Metabolic Diseases
Background:
- Observational studies suggest metformin may reduce breast cancer risk in diabetic patients.
- Metformin's potential as an anti-cancer agent has been investigated for decades.
- Despite research, its precise mechanisms and clinical efficacy in breast cancer are still ambiguous.
Purpose of the Study:
- To summarize findings on metformin's effects on breast cancer across translational studies.
- To identify factors contributing to heterogeneous outcomes in metformin research.
- To guide future research and identify patient subsets likely to benefit from metformin.
Main Methods:
- Review of in vitro, in vivo, and human studies on metformin and breast cancer.
- Analysis of factors influencing metformin's anti-cancer effects.
- Synthesis of existing data to explain outcome variability.
Main Results:
- Metformin's anti-cancer effects are modulated by dose, metabolic health, menopausal status, tumor subtype, and diet.
- Significant heterogeneity exists in study outcomes regarding metformin's efficacy.
- Key factors influencing metformin's role in breast cancer are identified.
Conclusions:
- Understanding modulating factors is crucial for interpreting metformin breast cancer research.
- Future studies should consider patient-specific variables for improved design.
- Identifying optimal patient subsets can enhance metformin's therapeutic application in breast cancer.
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