Abstract Background: The SWOG S1007 (RxPONDER) trial demonstrated that premenopausal women with hormone receptor-positive, Her2-negative breast cancer, 1–3 positive nodes, and Recurrence Score (RS) 26 benefit from adjuvant chemotherapy, but postmenopausal women do not. Most patients in RxPONDER underwent axillary lymph node dissection (ALND) to stage the axilla; however, axillary management has evolved. It is unclear whether the RxPONDER trial results were similar in patients who had sentinel lymph node biopsy (SLNB) only versus ALND. Methods: We performed a secondary analysis from RxPONDER to evaluate whether clinical outcomes differed between patients undergoing SLNB alone versus ALND. Endpoints included invasive disease-free survival (IDFS), distant relapse-free survival (DRFS), and locoregional recurrence (LRR). Results: Of 4980 women with available surgical data, 1847 (37%) had SLNB only, 707 (14%) ALND only, and 2426 (48.7%) both SLNB and ALND. Compared to the SLNB + ALND group, the SLNB-only group was older, postmenopausal, obese, and more likely to undergo partial mastectomy. Tumors were lower-grade, smaller, more often ductal, and less likely to be multicentric or have lymphovascular invasion (LVI). RS was similar across groups. SLNB-only patients had fewer nodes removed, less internal mammary node involvement, fewer positive nodes, and smaller SLN metastases. Those with a single positive node had a similar profile. On multivariate analysis, postmenopausal status and obesity increased the likelihood of SLNB alone; larger tumors and LVI decreased it. Among 1774 mastectomy patients, 352 had SLNB only; they were more often postmenopausal and obese, with otherwise similar features. IDFS, DRFS, and LRR were comparable across axillary surgery types after adjustment for clinical variables. In premenopausal SLNB-only patients (N=550), the chemotherapy arm had numerically improved IDFS (HR 0.68; 95% CI 0.43–1.07; p=0.09) and LRR (HR 0.45; 95% CI 0.14–1.42; p=0.17), though not statistically significant. This result is consistent with the main trial effect. Among SLNB-only patients who underwent partial mastectomy, 96% received adjuvant radiation. Conclusions: In this secondary analysis of RxPONDER, over one-third of patients underwent SLNB alone. These patients were older, more likely postmenopausal, and had more favorable tumors. Despite having less nodal surgery with fewer nodes removed, outcomes including IDFS, DRFS, and LRR were similar to those who underwent more extensive surgery. Among premenopausal patients, chemotherapy was associated with numerically better outcomes in the SLNB-only group, though not statistically significant. These findings support the safety of SLNB alone in selected patients and suggest further study in key subgroups.Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819 Citation Format: R. F. Hwang, W. E. Barlow, K. Kalinsky, R. Jagsi, L. Pusztai, A. Thompson, G. N. Hortobagyi, P. Sharma, F. Meric-Bernstam. Sentinel Lymph Node Biopsy and Clinical Outcome of Patients with Node-Positive Breast Cancer in the RxPONDER Trial (S1007) 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 PD12-05.
Hwang et al. (Tue,) studied this question.