A new systematic review and meta-analysis of phase III trials suggests menopause status can change outcomes with adjuvant CDK4/6 inhibitors in early hormone-receptor-positive breast cancer. The analysis focused on whether the effectiveness of CDK4/6 inhibitor–based regimens varies between premenopausal and postmenopausal patients, aiming to inform how clinicians individualize extended adjuvant strategies. For the CDK4/6 class, the work may sharpen real-world decision-making where treatment selection increasingly depends on biology and patient context rather than menopausal status alone.