In high-risk or metastatic cases in postmenopausal women, escalation often includes extended durations of adjuvant endocrine therapy (up to 10 years) with aromatase inhibitors (usually favored over tamoxifen when tolerated), which may be given in combination with CDK4/6 inhibitors in high-risk early-stage or metastatic disease. This evidence concerns the gene CDK4 and metastatic neoplasm.