Abstract 1Kalinsky K et al. RxPONDER (SWOG S1007), RS ≤25, HR+/HER2−, node+ BC. Cancer Res. 2023;83(5 Suppl):GS1-01 Background: The 21-gene Recurrence Score is a validated prognostic and predictive tool for breast cancer, with evidence supporting its utility over a 9-year follow-up. The RxPONDER1 trial further confirmed its clinical relevance in a controlled setting. However, its performance in real-world clinical practice remains underexplored. This study evaluates the application of the 21-gene Recurrence Score in routine care using RxPONDER1 criteria and determines whether its prognostic value remains in real-world data. Methods: We conducted a retrospective cohort study using prospectively collected data from Node-positive patients at the Norfolk and Norwich University, a tertiary referral cancer centre treating 650 breast cancer patients per year (2015-2024). Eligible patients were hormone receptor-positive, HER2-negative breast cancer patients with 1-3 positive lymph nodes and available 21-gene Recurrence Scores. Treatment and survival data were extracted from hospital records. Patients were stratified by menopausal status and recurrence score. Kaplan-Meier curves and Cox regression analyses assessed outcomes and compared with RxPONDER1 findings. Results: 282 patients were included. Chemotherapy was administered to all high-risk premenopausal patients (24.1%) and selectively to intermediate-risk patients based on additional clinical factors. In post-menopausal patients (75.9%), chemotherapy was primarily reserved for high-risk cases. High 21-gene Recurrence Scores (25) were significantly associated with poorer outcomes (HR 6.59, 95% CI 1.39-31.15, p = 0.017), intermediate scores (11-25) showed a non-significant trend (HR 2.38, p = 0.265). Endocrine therapy adherence was the strongest independent predictor of survival (HR 0.012, p = 0.004). Chemotherapy plus endocrine therapy (CET) showed no statistically significant benefit after adjustment (HR 1.82, p = 0.5) These findings align with RxPONDER1: chemotherapy showed no significant benefit in postmenopausal patients, but some benefit in premenopausal patients. Conclusions: The 21-gene Recurrence Score remains prognostic in node-positive patients and real-world outcomes mirror RxPONDER1 findings. Our study highlights the importance of endocrine therapy adherence and supports continued use of the 21-gene Recurrence Score for guiding chemotherapy decisions in clinical practice. Larger cohort real-world studies are needed to further validate these findings. Citation Format: R. Rodgerson, M. Youssef. Is the 21-Gene Recurrence Score Validated for Real-World use in Node Positive Breast Cancer? A Retrospective Cohort Study 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 PS5-05-25.
Rodgerson et al. (Tue,) studied this question.