Abstract PS3-10-14: Survival Outcome in Premenopausal ER+/PR+ HER2− Breast Cancer Stratified by Nodal Status: a National Cancer Database (NCDB) Experience

Abstract Background: The comparative benefit of chemotherapy (CT) versus endocrine therapy (ET) in premenopausal women with stage I-III estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), and HER2-negative (HER2-) breast cancer (BC) remains unclear. This study examined differences in survival outcomes among patients with node-negative (N0) and node-positive (N1) disease stratified by treatment modality. Methods: We analyzed data from NCDB for women <50 years with ER+ and/or PR+, HER2−, stage I-III BC from 2005 to 2018. Collected variables included tumor size, grade, nodal status, lymphovascular invasion (LVI), Charlson-Deyo comorbidity score, and treatment history (ET, CT, radiation therapy [RT]). Overall survival (OS) was estimated using Kaplan-Meier analysis and compared between CT and ET groups using the log-rank test. Multivariable Cox proportional hazards models were used to identify independent predictors of OS. Statistical significance was assessed using a two-sided α level of 0.05. Results: Among 376,303 eligible patients, 168,741 (44.8%) had N0 and 83,428 (22.2%) had N1 disease. Median age was 45 years (range: 18-50). In the N0 group, 71,733 (42.5%) received ET alone and 97,008 (57.5%) received CT. Compared to ET-only recipients, CT-treated patients were younger and more likely to have grade 3/4 tumors, larger tumor size, LVI, PR-negative disease, and no RT (P < 0.01). In the N1 group, 5,658 (6.8%) received only ET and 77,770 (93.2%) received CT. Similar trends were observed, although RT was more commonly given in CT recipients (P < 0.01). OS was superior in patients treated with ET alone versus CT across both nodal cohorts. Among N0 patients, 4-year OS was 99.2% with ET vs. 96.4% with CT, and 6-year OS was 97.3% vs. 92.7% (P < 0.0001 for both). In the N1 group, ET was associated with 4-year OS of 96.9% vs. 93.5% for CT, and 6-year OS of 91.0% vs. 87.0% (P < 0.0001 for both). On multivariable analysis (Table 1), larger tumor size, high grade malignancy, PR-negative status, heavy comorbidity burden, and absence of RT were associated with worse OS in all patients (P < 0.01). Interestingly, CT was independently associated with worse OS in N0 cohort but improved OS in N1 population. Conclusions: In premenopausal women with early-stage ER+/PR+, HER2- BC, ET alone was associated with superior OS in N0 disease. In contrast, CT improved OS in patients with N1 disease. These findings support the consideration of ET monotherapy as a potential alternative to CT in carefully selected N0 premenopausal patients. This work was limited by the inability to evaluate the role of ovarian function suppression. Future studies should explore the addition of ovarian suppression to ET as a strategy for safely omitting CT in N0 population. Citation Format: L. Lei, A. Marra, M. Canning, J. Switchenko, S. Gandhi. Survival Outcome in Premenopausal ER+/PR+ HER2− Breast Cancer Stratified by Nodal Status: a National Cancer Database (NCDB) Experience [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-10-14.