Efficacy of neoadjuvant endocrine therapy with CDK4/6 inhibitors in locally advanced breast cancer

BACKGROUND: Neoadjuvant treatment for hormone receptor (HR)-positive breast cancer remains limited, particularly for tumors that are insensitive to neoadjuvant chemotherapy. This study aims to compare the efficacy of neoadjuvant endocrine therapy combined with CDK4/6 inhibitors to that of traditional neoadjuvant chemotherapy. PATIENTS AND METHODS: A total of 49 patients receiving neoadjuvant endocrine therapy plus CDK4/6 inhibitors and 210 receiving neoadjuvant chemotherapy were enrolled. Magnetic resonance imaging was performed to assess tumor responses every 2-3 cycles of treatment. Propensity score matching (PSM) was performed to balance baseline characteristics. RESULTS: Both before and after PSM, the objective response rate (ORR) in the endocrine therapy group was comparable to that of the traditional chemotherapy group. After matching, the ORR was 64.6% (95% CI, 49.5-77.8) in the endocrine group and 56.3% (95% CI, 41.2-70.5) in the chemotherapy group (P = .532). A higher proportion of patients in the endocrine group achieved a pathological complete or near-complete response (Miller-Payne grades 4-5, 13.5% vs 10.4%) and post-treatment Ki67 < 5%, indicating a potential long-term benefit. Patients with ≥30% regression in maximal tumor diameter after 2 cycles of chemotherapy were considered chemotherapy sensitive. 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. CONCLUSION: Neoadjuvant endocrine therapy is a promising alternative for HR-positive breast cancer, especially for patients with poor responses to chemotherapy.