ERBB2 and breast carcinoma: Several mechanisms of resistance to trastuzumab have been uncovered in HER2-positive breast cancer, including the loss of trastuzumab binding site at the HER2 extracellular domain [43], PIK3CA mutation [44], PTEN loss [45], overexpression of RTKs [46], as well as the inhibitions of antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis [2].