The clinical benefits of using next-generation sequencing (NGS) in patients with metastatic BC (MBC) have led to many genomically targeted therapy approvals such as PI3K/AKT inhibitors for PIK3CA/AKT/PTEN-mutated tumors, PARP inhibitors for BRCA1/2 mutations and selective estrogen receptor downregulators (SERDs) for ESR1 mutations [[21], [22], [23], [24], [25]]. This evidence concerns the gene ESR1 and breast cancer.