Efficacy and Safety of Neoadjuvant Chemotherapy Followed by CDK4/6 Inhibitors Plus Endocrine Therapy in Patients With HR-Positive, HER2-Negative Breast Cancer: A Retrospective Single-Centre Cohort Analysis.

BACKGROUND: Endocrine therapy with CDK4/6 inhibitor has been the main treatment for HR+/HER2- breast cancer in the adjuvant setting; however, the data on the application in the neoadjuvant setting is limited. We compared neoadjuvant efficacy and safety of sequential chemotherapy-CDK4/6 inhibitors with chemotherapy alone in HR+/HER2- breast cancer patients. METHODS: Female patients with HR+/HER2- breast cancer who received neoadjuvant therapy at the Fifth Medical Center of the PLA General Hospital from November 2019 to March 2025 were enrolled. The objective response rate (ORR), pathological complete response (pCR), and event-free survival (EFS) between the two treatment groups were analyzed. RESULTS: Among the 181 enrolled patients, 142 received chemotherapy alone (NCT cohort) and 39 received CDK4/6 inhibitors plus endocrine therapy (NCT-ET cohort) after chemotherapy as preoperative therapy. Overall pCR was similar across cohorts (3.5% in NCT cohort vs. 2.6% in NCT-ET cohort, p = 1.000), as was ORR (72.5% vs. 69.2%, p = 0.685). The 3-year EFS rate was numerically higher in the NCT-ET cohort (96.7% vs. 83.6%, p = 0.111). However, among patients who failed to achieve partial response (PR) within 4 cycles of chemotherapy, switching to endocrine therapy was associated with improved ORR (61.3% vs. 30.4%, p = 0.005). Overall pCR (3.2% vs. 0.0%, p = 0.356) and 3-year EFS rate (95.7% vs. 78.0%, p = 0.105) were numerically higher in the NCT-ET cohort. The total incidence of grade ≥ 3 adverse effects was higher in the NCT-ET cohort (69.2% vs. 47.8%). However, for patient received endocrine therapy after chemotherapy, grade ≥ 3 events decreased from 66.7% during chemotherapy phase to 20.5% after switching to endocrine therapy. CONCLUSIONS: Despite no statistically significant differences in observed overall pCR and 3y-EFS between patients treated with NCT or NCT-ET, the sequential endocrine strategy was associated with improved ORR among patients who did not achieve PR after four cycles of chemotherapy and a lower incidence of adverse events during endocrine therapy.