It is important to note that publicly available data [46, 47] demonstrates that approximately 21% of HER2-amplified cases of breast cancer also harbor a mutation at one of the hotspots of PIK3CA. Our results suggest that HER2+ tumors with helical domain mutations of PIK3CA will respond to tyrosine kinase inhibitors such as lapatinib and neratinib whereas HER2+ tumors with H1047R mutations will not, although both a hypersensitive to resistance mediated by NRG1β. Here, ERBB2 is linked to breast cancer.