PTEN and carcinoma: These include for example in vivo conversion of HER2+ to HER2- carcinoma after neoadjuvant trastuzumab [12], predominance of the constitutively active HER2 form (p95HER2) [8], overexpression or hyperactivation of other HER family receptors or its ligands [13], amplification of the PI3K/AKT/mTOR pathway by loss of phosphatase and tensin homolog (PTEN) [14], gain-of-function mutation in PI3KCA (encoding the PI3K catalytic isoform p110α) [15] and AKT mutations or amplifications [16].