Gene signature of metformin actions on primary breast cancer within a window of opportunity randomized clinical trial.

560 Background: Metformin has been linked to a reduced incidence of breast cancer and to increased pathological response when administered concurrently with neoadjuvant chemotherapy. The antineoplastic effect of metformin may be through direct activation of AMP-activated protein kinase (AMPK), since AMPK is dysfunctional in the majority of primary breast cancers, or via systemic effects. This open label, randomised clinical trial investigated the effects of metformin alone on gene expression in primary breast cancer. Methods: Nondiabetic women with histologically proven, operable, primary invasive breast cancer > 1 cm in size were offered the trial. The trial had 2 arms: trial A (8 patients), patients had tumor core biopsies (1) at presentation; (2) after a week of no treatment (internal control); and (3) after 2 weeks of metformin at the time of definitive surgery. In trial arm B (47 patients), patients had paired core biopsies and venous blood for insulin levels: before randomisation to either take metf...