The clinical efficacy of the endocrine therapy, either non steroidien aromatase inhibitors and fulvestrant combined with CDK4/6 inhibitors represent a standart of care, for premenopausal or menopausal patients with an estrogene receptor positive, HER2 negative (ER + /HER2-) advanced breast cancer (BC) [15–18]. The gene discussed is ESR1; the disease is breast cancer.