Later, it was found that there was ESR1 gene mutation in about 36% of metastatic ER+ BC,[74] and most mutations were detected in patients treated with AIs.[75] The emergence of ERα mutant will reduce the sensitivity of patients to endocrine therapy, which is mainly related to the ligand-independent activation, and at the same time, the affinity for drugs will decrease to varying degrees. This evidence concerns the gene ESR1 and breast cancer.