Adjuvant chemotherapy (CT) benefit in invasive lobular carcinoma (ILC) by Oncotype DX Recurrence Score and menopausal status.

540 Background: The benefit of adjuvant CT in early-stage hormone receptor–positive (HR+) and HER2-negative (HER2–) ILC remains uncertain. The predictive utility of the Oncotype DX Recurrence Score (RS), widely used to guide CT decisions in HR+/HER2 BC, remains debated in ILC. To address these gaps, we analyzed the impact of adjuvant CT on overall survival (OS) across RS categories and by menopausal status. Methods: We queried the National Cancer Database for patients (pts) with early-stage HR+/HER2– ILC who had surgery between 2010 and 2021. Pts were grouped by receipt of adjuvant CT (CT+ vs CT–). Analyses were stratified by RS (low 0–15, intermediate 16–25, high ≥26) and menopausal status, using age (<50 vs ≥50 years) as a proxy. Overlap propensity score weighting (OPSW) balanced baseline covariates (race, ethnicity, comorbidities, clinical T and N stage, grade and radiation and hormone therapies), and OPSW Cox models assessed the association between time-varying adjuvant CT and OS. Results: Among 141,949 pts with ILC, 19.6% received adjuvant CT. The CT+ cohort was younger (median age 59 vs 67 years) and more often pre-menopausal (21.8 vs 9%), and had high grade tumors (8.7 vs 3.3%), advanced T stage (T2: 39.4 vs 21.8%; T3: 14.9 vs 3.4%), node-positive (N1-3: 22 vs 3.2%) disease and more frequently received radiation (74.6 vs 56.5%) and hormone therapy (93.3 vs 87.5%), all p<0.001. RS testing was available in 38% of pts; CT+ cohort more often had high (9.2 vs 1.2%) or unknown RS (75.4 vs 57.9%), p<0.001. In the high RS group, CT was associated with improved 5-year (93.3 vs 90.5%) and 10-year OS (79.4 vs 71.7%) and lower mortality (adjusted hazard ratio (aHR) 0.69, p <0.001) (Table 1). Among postmenopausal pts, the survival benefit with CT was greatest in pts with high RS (10-year OS: 78.6 vs 69.2%; aHR 0.65, 95% CI 0.52–0.82, p=0.0003). No OS benefit was observed in low (aHR= 1.16, p= 0.31) or intermediate (aHR= 1.07, p= 0.39) RS groups. Among premenopausal pts, CT benefit was limited to the intermediate RS group (10-year OS: 94.9 vs 91.3%; aHR 0.57, 95% CI 0.33–1.00, p=0.049); no benefit was observed in low (aHR= 1.11, p= 0.77) or high (aHR= 1.50, p= 0.55) RS. Conclusions: In early-stage HR+/HER2– ILC, RS has limited clinical utility. Adjuvant CT benefit was restricted to pts with high RS, predominantly in postmenopausal pts, while RS did not reliably predict benefit in premenopausal pts. No OS benefit was seen in low RS disease, supporting a selective, biology-driven approach to CT use in ILC. CT decisions in pts with unknown RS appear largely driven by clinicopathologic factors. 10-year survival analysis of ILC patients based on CT receipt and RS. RS group OS (%, 95% CI) CT + OS (%, 95% CI) CT - aHR (95% CI) Reference: CT- p-value Low 87.6 (84.6-90.6) 88.9 (88.0-89.9) 1.13 (0.87-1.47) 0.36 Intermediate 86.2 (84.4-88.1) 86.5 (85.3-87.7) 1.02 (0.87-1.20) 0.78 High 79.4 (76.4-82.5) 71.7 (66.9-76.8) 0.69 (0.55-0.87) <0.01