Many potential mechanisms of trastuzumab resistance in HER2-positive BC have been proposed which have been discussed in detail by us and others [2, 5]; including altered intracellular signaling involving loss of PTEN, reduced p27kip1, increased PI3K/Akt activity (e.g. PIK3CA mutations) or altered signaling via non-HER family receptor tyrosine kinases such as IGF1R. This evidence concerns the gene ERBB2 and breast cancer.