ESR1 and breast cancer: Estrogen receptors (ER) blockade induced by endocrine therapy can lead to reactivation of the HER receptor tyrosine kinase pathway, thus prolonging HER pathway blockade improves the prognosis of HER-2 positive and HR-positive BC(Sudhan et al. 2019).In addition, neratinib can overcome the drug resistance of trastuzumab and traditional chemotherapy drugs(Gamez-Chiachio et al. 2022).