Frequent causes for intrinsic or aquired endocrine resistance in ER+/HER2- breast cancer include increased growth factor receptor signaling that results in ligand-independent ERα activation, genomic alterations involving the ERα gene ESR1 such as ESR1 gene re-arrangements with other genes, ESR1 amplifications and ESR1 recurrent point mutations [19]. The gene discussed is ESR1; the disease is breast carcinoma.