In addition, oncogenic activation of PIK3CA leads to intrinsic resistance of HER2-positive breast cancer cells to HER2 inhibition (Berns et al., 2007; Hanker et al., 2013), and is more frequently activated in patients that exhibit acquired resistance to HER2 inhibition (Chandarlapaty et al., 2012). This evidence concerns the gene ERBB2 and breast cancer.