Corleto Karen A, Strandmo Jenna L, Giles Erin D
Department of Nutrition, Texas A&M University, College Station, TX 77843, USA.
School of Kinesiology and Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Pharmaceuticals (Basel). 2024 Mar 19;17(3):396. doi: 10.3390/ph17030396.
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.
在过去几十年里，越来越多的研究探讨了将抗糖尿病药物二甲双胍重新用于预防和/或治疗乳腺癌的可能性。21世纪初的观察性研究表明，服用二甲双胍的糖尿病患者患癌风险降低，这为支持二甲双胍作为抗癌药物的潜在作用提供了首个证据。尽管付出了巨大努力，但二十年后，二甲双胍对乳腺癌的确切机制和临床疗效仍不明确。在此，我们总结了从研究二甲双胍对乳腺癌影响的研究中得出的关键发现，这些研究涵盖了从体外、体内到人体研究的转化范围。重要的是，我们讨论了可能有助于解释研究结果显著异质性的关键因素，强调了二甲双胍剂量、潜在代谢健康状况、绝经状态、肿瘤亚型、膜转运蛋白表达、饮食和其他因素如何可能在调节二甲双胍的抗癌作用中发挥作用。我们希望这些见解将有助于解释已完成研究的数据，改进未来研究的设计，并有助于识别最有可能从二甲双胍治疗中获益的乳腺癌患者或高危人群。
