Interestingly, it has been shown that, in breast cancer patients, alterations of phosphatidylinositol 3-kinase (PIK3)-pathways can induce resistance to anti-HER2 therapies [102,103,104] and that mutations of the catalytic subunit of PIK3 (PIK3CA) can be present in the metastasis but not in the primary tumor [105]. This evidence concerns the gene ERBB2 and breast carcinoma.