Abstract Background The TAILOR-X trial demonstrated that clinical risk scores incorporating histologic grade and tumor size provided additional prognostic stratification in premenopausal, node-negative breast cancer patients with 21-gene recurrence scores (RS) of 16-25. We evaluated the prognostic significance of tumor grade in patients with node-negative, hormone receptor-positive (HR+), and human epidermal growth factor receptor 2 (HER2)-negative breast cancers treated according to RS-guided strategies. Patients and Methods In this multicenter retrospective cohort study, we analyzed 1,944 patients with node-negative, HR+/HER2− breast cancer treated between 2011 and 2020 at two academic centers. The recurrence-free interval (RFI), defined as the time from diagnosis to the first invasive local, regional, or distant recurrence, was analyzed by tumor grade, stratified by age (≤ 50 vs. 50 years), and RS category. Results Among all patients, a high tumor grade was associated with a shorter RFI (P 0.001). This association was evident in patients aged ≤ 50 years (P 0.001) but not in those aged 50 years. In 802 women aged ≤ 50 with intermediate RS (11-25), high-grade tumors were associated with adverse features, including lymphovascular invasion, high Ki-67 expression, and chemotherapy receipt, and demonstrated reduced RFI (P 0.001). In this subgroup, tumor grade remained an independent prognostic factor in multivariable analysis (hazard ratio, 6.96; 95% confidence interval, 2.69-17.99), particularly in patients who did not receive chemotherapy. Conclusion A high tumor grade was associated with increased tumor recurrence in younger node-negative patients with an intermediate RS. These findings support the incorporation of histological grade into prognostic assessment and treatment decision-making in this group. Citation Format: S. Bae, S. Lee, Y. Kook, A. Kim, J. Jeong, S. Lee, S. Ahn. Prognostic implication of tumor grade in patients with node-negative breast cancer aged ≤ 50 years with 21-gene recurrence scores of 11-25 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 PS3-07-20.
Bae et al. (Tue,) studied this question.