Abstract 1Sparano JA et al. TAILORx trial: endocrine vs chemoendocrine therapy in HR+/HER2− breast cancer Background: The TAILORx 1 trial established the 21-gene Recurrence Score as a key tool for guiding chemotherapy decisions in node negative, hormone receptor-positive, HER2-negative breast cancer. While its prognostic utility is well supported in clinical trials, its real-world validation remains limited. This study evaluates the 21-gene Recurrence Score's performance in a real-world cohort and compares outcomes with TAILORx 1 -defined risk groups. Methods: We conducted a retrospective cohort study using prospectively collected data of 388 node-negative patients who underwent 21-gene Recurrence Score testing between 2015 and 2024 in a tertiary referral cancer centre. Patients were stratified into five groups based on TAILORx 1 criteria: Group A (Age 50, RS 11-25), Group B (Age ≤ 50, RS 11-15), Group C (Age ≤ 50, RS 16-25), Group D (RS 0-10 all ages), Group E (≥ 26 all ages). Treatment data (Endocrine Therapy ET vs. Chemotherapy + ET CET) and survival outcomes were analysed using Kaplan-Meier, log-rank tests and cox regression. Results: Group A (n=151) showed slightly more events than expected (10 observed vs. 8.2 expected), but outcomes remained consistent with TAILORx1, which found no chemotherapy benefit in this group. Group B (n=22) had significantly worse outcomes than expected (HR 6.51, p=0.021), contrasting with TAILORx1, where this group had excellent survival with ET alone. Group C (n=42) had no events, suggesting better-than-expected outcomes. Group D (RS 0-10) also showed fewer events than predicted. Group E (RS ≥26) outcomes aligned with TAILORx1, supporting chemotherapy use. Multivariable analysis identified CET (HR 4.25, p=0.034) and intermediate risk (HR 9.31, p=0.036) as significant predictors of poorer outcomes, likely reflecting treatment selection bias. Conclusions: Our real-world data largely align with TAILORx1, confirming the prognostic value of the 21-gene Recurrence Score in node-negative patients. However, worse-than-expected outcomes in group B suggest biological heterogeneity or treatment adherence issues. These findings support continued use of the 21-gene Recurrence Score for risk stratification and highlight the need for careful clinical judgement in younger patients. Larger studies are warranted to validate these trends. Citation Format: R. Rodgerson, M. Youssef. Real-world validation of the 21-gene Recurrence Score in Node Negative Breast Cancer: A Comparative Analysis with TAILORx 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 PS5-05-24.
Rodgerson et al. (Tue,) studied this question.