Metformin in early breast cancer (BC): A prospective, open-label, neoadjuvant “window of opportunity” study.

1019 Background: There is growing evidence that metformin may exert anti-cancer effects through indirect (insulin-mediated) or direct (insulin-independent) mechanisms. Here, we report final results of a neo-adjuvant “window-of-opportunity” study of metformin in women with operable BC. Methods: Newly diagnosed, untreated, non-diabetic BC patients received metformin 500 mg tid after diagnostic core-biopsy until definitive surgery(no other treatment). Clinical [weight, symptoms, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C-30)] and biologic characteristics [insulin, glucose, homeostatic model assessment (HOMA), C-reactive protein (CRP), leptin] were compared pre- and post-metformin as were Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL, an apoptotic marker) and Ki67 (primary end-point) scored blinded by manual count of positive nuclear-staining. The planned sample-size of 40 patients gave 90% power to detect a 5.5 percenta...