Future studies in larger clinical cohorts are needed to confirm the functional significance and clinical consequences of ESR1 amplification in both primary and metastatic HR+ HER2- BC specimens, and to investigate its clinical relevance in terms of tumor sensitivity/resistance to standard first-line therapies, i.e., CDK4/6 inhibitors in combination with AIs or fulvestrant [34–39], in the treatment of advanced BC patients. This evidence concerns the gene CDK4 and neoplasm.