The combination of cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) with endocrine therapy (ET) has emerged as an effective alternative to neoadjuvant chemotherapy (NCT) for patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2) -negative breast cancer (BC). The gene discussed is CDK4; the disease is breast cancer.