Moreover, studies have shown that long-term use of trastuzumab + pertuzumab + buparlisib (PI3K inhibitors) combination treatment in HER2+/PIK3CAH1047R transgenic mice with breast cancer produces buparlisib resistant tumors (Hanker et al., 2017; Wang and Xu, 2019). Here, ERBB2 is linked to breast carcinoma.