Metformin: a pharmacological approach integrating hyperinsulinemia breast cáncer at the molecular, cellular clinical levels*

The possibility exists to adopt insulin reduction for preventive and therapeutic purposes in breast cancer. In this regard, recent interest has been focused on the insulin sensitizer metformin, a biguanide derivative that significantly reduces breast cancer incidence and improves breast cancer patient's survival in type 2 diabetics. The ability of metformin to activate AMP-activated protein kinase (AMPK), a key regulator of energy balance in the single cell and the whole organism, largely explains metformin's anti-breast cancer activity. Here, we review the multifaceted and redundant mechanisms through which metformin-reprogrammed energy metabolism at both the organismal and the cellular level may constitute a novel and valuable strategy to prevent and treat breast cancer disease.