Abstract Background: The RxPONDER trial was a landmark study demonstrating that the 21-gene Oncotype DX (ODX) assay can help avoid unnecessary adjuvant chemotherapy in postmenopausal women with 1-3 positive nodes (N+) and an ODX recurrence score (RS) ≤25. However, N+ premenopausal women with RS≤25 showed a significant but variable benefit to adjuvant chemotherapy despite low or intermediate ODX RS. Current NCCN guidelines therefore recommend ODX only as a consideration in this subgroup, leaving risk-adapted decision-making unresolved. Ataraxis Breast (ATX) is a multi-modal artificial intelligence test that integrates morphological features extracted from standard H0.01). The estimated 5-year recurrence rates for ATX bottom and top quartiles were 9.1% and 25.7%. When divided into exploratory low/high ATX risk groups with threshold at 10% 5-year risk of recurrence (RoR), the ATX 10% RoR group included 39 patients with an observed recurrence rate of 5%, while ATX ≥ 10% RoR included 111 patients with an observed recurrence rate of 16%. Conclusions: ATX demonstrates promising independent prognostic performance in premenopausal node-positive breast cancer across diverse datasets. Larger studies are needed to confirm its efficacy and utility. Citation Format: J. Elayoubi, K. Choucair, K. Kalinsky, K. Pogoda, F. J. Esteva, K. Zeng, J. Cappadona, B. Machura, K. J. Geras, J. Witowski. Prognostic performance analysis of artificial intelligence test and 21-gene assay in premenopausal node-positive HR+ HER2- breast cancer patients 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 PS3-06-17.
Elayoubi et al. (Tue,) studied this question.