Metformin Treatment for the Prevention and/or Treatment of Breast/Mammary Tumorigenesis.

There is increasing interest in metformin's effects on the development, treatment and/or progression of breast cancer. This emerges from observational studies that diabetic women treated with metformin in comparison to other antidiabetic compounds had lower breast cancer incidence and/or mortality rates. The mechanism of action is considered to be activation of hepatic AMPK resulting in reduced gluconeogenesis. Calorie restriction, which consistently reduces mammary tumorigenesis in rodents, is also thought to act through this pathway leading to the hypothesis that metformin's anticancer effects are mediated in a similar fashion. Here we review the literature evaluating metformin's anticancer effects in relation to breast/mammary tumorigenesis. We include clinical observations, as well as studies utilizing rodent models and mammary cell lines. In addition to the anticancer effect of metformin mediated through the AMPK pathway, additional mechanisms of action that directly target tissues have been identified including effects on stem cells, apoptosis, STAT3 and HER2.