Among patients with tumors less sensitive to chemotherapy, sequential treatment with neoadjuvant endocrine therapy plus CDK4/6 inhibitors significantly improved ORR (61.8% vs 32.4%, P = .028) and was associated with greater Ki67 reduction and improved Miller-Payne grades.<h4>Conclusion</h4>Neoadjuvant endocrine therapy is a promising alternative for HR-positive breast cancer, especially for patients with poor responses to chemotherapy. Here, CDK4 is linked to breast cancer.