More recently, the ESR1 mutations have been associated with as a resistance mechanism for endocrine therapy, which are clustered in the ligand-binding domain of the receptor, and result in ligand-independent estrogen receptor activity.[24,75] The ESR1 mutations are rare in primary patients with BC without metastasis, but are more commonly found in patients with metastatic BC or metastatic BC after endocrine therapy.[75] In this meta-analysis, the ESR1 mutations were analyzed only in patients with advanced or metastatic BC. This evidence concerns the gene ESR1 and breast cancer.