Metformin, insulin, breast cancer and more

EVALUATION OF: Goodwin PJ, Pritchard KI, Ennis M, Clemons M, Graham M, Fantus IG: Insulin-lowering effects of metformin in women with early breast cancer. Clin. Breast Cancer 8(6), 501-505 (2008). This paper demonstrates that in breast cancer patients without overt diabetes mellitus, the antidiabetic biguanide metformin at a dose of 1500 mg/day reduces initially increased fasting insulinemia by 22.4% on average, 6 months after the onset of treatment. Since the same authors reported earlier on the association between preoperational insulinemia and breast cancer progression rate, an important conclusion from the above publication was that a Phase III randomized trial of metformin is warranted in order to assess the possible antitumor effect of this preparation. The evaluation presented below briefly addresses the history of the issue and possible targets of metformin effects beside its insulin-related action. It is argued that in selecting breast cancer patients for metformin therapy, one should take into account, along with the standard criteria, the pharmacogenetic aspects, estrogen production and specific features of estrogenic signaling, and also the expression of important metformin targets, including AMP-activated protein kinase, in tumor tissue.