Abstract PS4-08-04: Impact of adjuvant chemotherapy in the survival outcomes of early-stage hormone receptor (HR)-positive HER2-negative lobular versus ductal carcinoma patients

Abstract Background: Invasive lobular carcinoma (ILC) represents 10-15% of all breast cancers (BC) and differs biologically and clinically from invasive ductal carcinoma (IDC). Conflicting data exist with regard to variation in prognosis and benefit of chemotherapy (CT) between these histologic subtypes. Here, we compare the impact of adjuvant CT on survival outcomes in patients (pts) with early-stage (ES) HR+/HER2- ILC and IDC. Methods: We queried the National Cancer Database for pts who received upfront surgical resection for ES HR+ HER2- invasive BC between 2010 and 2021, classifying cohorts into ILC or IDC subtypes. Cox proportional hazards models assessed the relationship between overall survival (OS) and histology type adjusting for potential confounders including age, race, stage, grade, and treatment variables. Subgroup analyses were performed based on CT receipt and Oncotype DX recurrence score (RS), a genomic assay used to predict response to CT, categorized as (low (L) 0-15, intermediate (I) 16-25, high (H) >=26). Results: Of the 1,101,920 pts included, 14.7% (n= 162,430) had ILC. Compared to pts with IDC, the ILC cohort was comprised of a greater proportion of Whites (87.7 vs 85.4%), intermediate-grade (63.7 vs 48.8%), clinical T2 (26.5 vs 22.1%) and N0 disease (89.1 vs 88.3%) (all p<0.001). RS scores varied by histologic subtype with a greater proportion of ILC having L (17.9 vs 17.2%) and I RS (15.2 vs 11.9%) compared to IDC, in which H RS was more common (2.8 % ILC vs 5.8% IDC). Use of adjuvant CT (79.6 vs 77.3%) and hormonal therapy (89.3 vs 86.4%) was higher in ILC, while radiation use was lower (61.3 vs 64.5%) (all p<0.001). The 5-year (Y) OS of ILC was similar to IDC (89.5 (89.3-89.7) vs 90.4 (90.3-90.5) %), however 10Y OS was worse for ILC cohort (73.6 (73.3-74.0) vs 76.7 (76.6-76.9) %, p <0.001). Among pts who received adjuvant CT, at 5 Y, OS was nearly identical between ILC and IDC across all RS groups. However, at 10 Y, OS was consistently lower in ILC compared to IDC, with a more pronounced difference in the I and H RS groups (Table 1). While OS was lower in ILC pts who received CT compared to IDC pts that received CT in univariate analyses of the overall cohorts (HR: 1.16, p<0.001) and when stratified by RS (L - 1.07, p= 0.01; I - 1.18, p<0.001; H - 1.12, p = 0.02), these associations did not retain significance when adjusting for clinically relevant confounders (HRs: Overall - 1.01, p= 0.16; L - 0.98, p= 0.52; I - 0.95, p= 0.11; H - 0.97, p= 0.51). An interaction was observed between histology type and stage (p = 0.0026). Conclusion: Our study suggests that while 5-year survival may be comparable, ES ILC pts receiving adjuvant CT may experience worse long-term outcomes compared to IDC, particularly among those with higher genomic risk. Further research is needed to personalize treatment strategies for ILC by identifying underlying molecular differences that drive this disparity. 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, D. Stover, N. Williams. Impact of adjuvant chemotherapy in the survival outcomes of early-stage hormone receptor (HR)-positive HER2-negative lobular versus ductal carcinoma patients [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 PS4-08-04.