In fact, the analysis of a group of breast cancers with amplified HER2 with disease recurrence after trastuzumab treatment provided evidence regarding a high frequency of abnormalities of the PI3K pathway; 71% of patients exhibiting PI3KCA mutations and/or loss of PTEN expression; this value has to be compared to 44% in an unexposed cohort of HER2-amplified tumors [292]. This evidence concerns the gene PIK3CD and breast cancer.