“…Administration of metformin (1500 mg, daily, NCT00930579, phase II, Table 2) to 35 non-diabetic overweight women (BMI ≥ 25 kg/m 2 ) with breast cancer (stages 0-III) showed no significant difference in the tumor proliferation index (Ki67) when compared to age, BMI, and stage matched historic controls, despite a significant reduction in BMI, cholesterol, and leptin levels in the metformin-treated subjects [158]. Increase in the levels of Raptor, C-Raf, Cyclin B1, Cyclin D1, TRFC, and Syk; while reduction in the levels of pMAPK pT202, Y204 , JNK pT183, pT185 , Bad pS112 , PKCα pS657 , and Src pY416 was observed in the metformin administered (1500 mg, daily, NCT00930579, phase II, Table 2) non-diabetic overweight women with breast cancer when compared to age, BMI, and stage-matched historic controls [159]. This is indicative of the fact that in a clinical setting, metformin administration can influence cancer cell apoptosis, cell cycle, cell signaling, and invasion [159].…”