ESR1 and breast cancer: According to previous studies, promotion of HER2 downstream signaling pathways such as PI3K/Akt, activation of alternate receptor pathways such as EGFR, crosstalk between estrogen receptor and HER2, and alterations in apoptosis and cell cycle control contribute to breast cancer resistance to trastuzumab (Pohlmann et al., 2009; Wong and Lee, 2012; Luque-Cabal et al., 2016).