Abstract Background: Invasive lobular carcinoma (ILC) accounts for 10-15% of breast cancer (BC) cases and is predominantly hormone receptor-positive (HR+) and HER2-negative (HER2-). Although existing data indicates that ILC is less responsive to chemotherapy (CT) than invasive ductal carcinomas, the benefit of adjuvant CT in early-stage (ES) ILC is incompletely characterized. Further, the utility of the Oncotype DX Recurrence Score (RS), which has been used to predict response to CT in HR+/HER2- BC, has been debated for ILC. To address these issues, we studied the role of adjuvant CT on overall survival (OS) and by RS categories in ES ILC. Methodology: We queried the National Cancer Database for patients (pts) with ES HR+ HER2- ILC who underwent upfront surgical resection between 2010-2021. Pts were categorized to two cohorts based on receipt of adjuvant CT (CT+ and CT-). Subgroup analyses were performed based on RS score categories: low (L) 0-15, intermediate (I) 16-25, high (H) ≥26). Kaplan-Meier curves and log-rank tests determined OS between cohorts. Multivariate Cox proportional hazards models assessed OS, adjusting for potential confounders including age, race, stage, grade, and treatment variables. Results: Of the 162,430 ILC pts identified, 79.6% received adjuvant CT. The CT+ cohort were more likely to be younger pts (median age, IQR: 65 (55, 75) vs 66 (56, 72) years), have fewer comorbidities (Charlson-Deyo score (CDS) 0: 82.5 vs 82.3%, CDS 1: 13.1 vs 12.6%), intermediate grade disease (64.1 vs 62.2%), tumors 2 cm (67.1 vs 50.7%), clinically node negative disease (92.0 vs 77.7%), and receive radiation (63.5 vs 52.3%), and hormonal therapy (98.4 vs 51.4%), (all p0.001). In the CT+ cohort, more pts had RS L (20.2 vs 8.9%), I (17.1 vs 7.5%), H (3.1 vs 1.7%) compared to CT-cohort (p0.001). CT receipt conferred higher 5-year and 10-year OS. This survival benefit with adjuvant CT was observed among all RS groups with the highest benefit observed in H RS group (10Y OS: 84.5 vs 63.9%, p0.001) ( Table 1). In multivariate analysis adjusting for relevant confounders, receipt of adjuvant CT was associated with decreased morality in the overall ILC cohort (Hazard ratio (HR), 95% CI: 0.79, 0.76-0.83, p0.001) and the RS subgroups, though not statistically significant in L RS group (HR, 95% CI: L - 0.77, 0.59 - 1.01, p= 0.06; I - 0.78, 0.62 - 0.98, p= 0.04; H - 0.67, 0.50 - 0.89, p= 0.006). Conclusion: In this study, adjuvant CT was associated with improved OS in ILC pts with RS 15. These data support use of RS for CT decision-making in appropriate candidates. Further investigations are needed to identify ILC pts who would benefit the most from adjuvant CT. Citation Format: A. Roy, Y. Gokun, B. Slover, N. Lopetegui-Lia, D. Quiroga, G. Bader, M. Cherian, A. Davenport, K. Johnson, S. Sardesai, R. Wesolowski, S. Myers, E. Burke, M. Gatti-Mays, N. Williams, D. Stover. Benefit of adjuvant chemotherapy for early-stage hormone receptor positive and HER2 negative lobular breast cancer patients: Analysis based on genomic risk scores 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 PS2-02-06.
Roy et al. (Tue,) studied this question.