Prognostic implication of tumor grade in patients with node-negative breast cancer aged ≤ 50 years with 21-gene recurrence scores of 11–25

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 1944 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-grade tumor 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 tumor was associated with adverse features, including lymphovascular invasion, high Ki-67 expression, and chemotherapy receipt, and demonstrated reduced RFI ( P < 0.001). In this subgroup, high-grade tumor remained an independent factor for poor RFI 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-grade tumor was associated with increased tumor recurrence in younger node-negative patients with an intermediate RS. These findings support the incorporation of tumor grade into prognostic assessment and treatment decision-making in this group.