ERBB2 and breast cancer: Some potential mechanisms of trastuzumab resistance include mutational activation of the phosphatidylinositide 3-kinase (PI3K)/AKT pathway [16], up-regulation of insulin-like growth factor receptor (IGFR) and hetero-dimerization of IGFR/HER-2 [17,18], loss of phosphatase and tensin homolog gene (PTEN) function [19], and accumulation of truncated HER-2 receptor (p95HER-2) [20], all of which have been verified as principal pathways in breast cancer.