- To determine the in situ biologic effect of metformin hydrochloride on the AMP kinase, MTOR/PI3K, and IGF pathways in breast cancer (tissue S6K and phospho S6K, p53, p63, and p73 levels as well as p53 [(Ser-15), if wild-type p53 is present], p63 [Ser-66/68, Ser-301, and Ser-361], and p73 [Y-99] phosphorylation, PTEN [clone 6H2.1], phospho-Akt [S473], insulin receptor substrate 1 and 2 [IRS-1 and IRS-2], and LKB1).