A decrease in circulating insulin levels may also result in the downregulation of INSR signaling pathways in cancers expressing INSR and attenuation of the proliferative and anti-apoptotic signals117, 118 Supporting such a possibility, non-diabetic breast cancer patients given metformin for 6 months displayed an average 22% reduction in insulin levels.119 Moreover, a 2-week administration of metformin in between diagnosis and surgery led to a reduction in circulating insulin levels, a decrease in INSR expression and downregulation of AKT and MAPK signaling pathways in their tumors.117. This evidence concerns the gene INS and breast carcinoma.