Does neoadjuvant chemotherapy matter in endocrine-sensitive breast cancer?: Insights from a 10-year SEER cohort.

e12626 Background: In ER+/HER2– breast cancer, neoadjuvant chemotherapy (NAC) is used far less frequently than in other biologic subtypes, largely because endocrine-sensitive tumors usually have favorable biology and show excellent long-term outcomes with surgery and endocrine therapy alone. NAC is sometimes pursued for downstaging, especially in large T3 tumors or when breast conservation is desired. However, whether NAC provides a meaningful overall survival (OS) benefit in T2–T3, N0–1 ER+/HER2– disease remains uncertain. This study evaluates the association between NAC and OS using contemporary, population-level data. Methods: We conducted a retrospective cohort analysis using SEER Research Plus 17 registries (2000–2022; Nov 2024). We included patients with T2 or T3, N0–1, M0, ER+/HER2– breast cancer diagnosed between 2013-2022. Patients were grouped by receipt of NAC versus no NAC. Five-year OS was estimated using Kaplan–Meier methodology and compared with log-rank testing. Analyses were stratified by T2 and T3 tumor status. Results: A total of 5,792 patients met criteria. In the T2 subgroup, 1,631 patients received NAC and 3,761 did not. Five-year OS was 84.3% with NAC versus 87.1% without NAC, a statistically significant difference favoring omission of NAC (Z = 3.944; p = 0.00004). In the T3 subgroup (398 NAC vs 514 no NAC), five-year OS was 74.5% for those receiving NAC compared with 84.3% among patients not treated with NAC (Z = 1.743; p = 0.04). Across both tumor sizes, NAC did not confer a survival advantage; instead, OS consistently favored patients treated without NAC, including those with larger tumors where downstaging considerations often influence treatment decisions. Conclusions: In this population-based analysis, neoadjuvant chemotherapy did not improve overall survival in ER+/HER2– T2–T3, N0–1 breast cancer and was associated with worse outcomes compared with no NAC. These findings highlight the limited value of NAC in endocrine-sensitive disease and support a selective, biology-driven approach rather than relying on tumor size alone. Interpretation is limited by SEER’s lack of data on progression-free survival, locoregional recurrence, treatment intent, genomic assays, and endocrine therapy adherence. Prospective studies are needed to determine whether any subgroup of these patients derives meaningful benefit from NAC.