Abstract GS2-01: More versus less invasive axillary surgical staging procedures in breast cancer patients converting from a clinically node-positive to a clinically node-negative stage through neoadjuvant chemotherapy - primary endpoint analysis of the international prospective multicenter AXSANA/EUBREAST 3(R)study

Abstract Introduction In breast cancer patients converting from clinically positive (cN+) to negative (ycN0) lymph node status after neoadjuvant chemotherapy (NACT), surgical staging by axillary lymph node dissection (ALND) is increasingly replaced by less invasive procedures like targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB), possibly followed by completion ALND or regional radiotherapy if positive. Prospective data comparing oncologic safety of different procedures as a primary approach after NACT are currently scarce. We report 3-year axillary recurrence-free survival (ARFS) as the first primary endpoint analysis of the AXSANA/EUBREAST 3(R) study (NCT04373655, www.eubreast.org/axsana), initiated by the European Breast Cancer Research Association of Surgical Trialists (EUBREAST e.V.). Methods In an international multicenter cohort study, patients with cN+ breast cancer who receive at least four cycles of NACT and convert to ycN0 are eligible. Axillary staging after NACT is performed according to institutional routine. Grouping of patients was based on the primary staging procedure, not on final axillary surgery, e.g., completion ALND following a positive SLNB was classified as SLNB. Co-primary endpoints are ARFS, invasive breast cancer-specific survival (iBCSS), and patient-reported quality of life. Data entry is systematically monitored. Less extensive axillary staging procedures as first surgery after NACT (TAD, SLNB, targeted lymph node biopsy (TLNB)) are considered non-inferior to staging by ALND if the lower bound of a two-sided 90% confidence interval (CI) around 3-year ARFS exceeds 97%. 750 patients were required per group (TAD/SLNB/TLNB vs ALND). Results From June 2020 to April 2025, 6,474 patients (26 countries, 288 study sites) were enrolled, 2,632 of whom had completed surgery by December 31, 2023 and were selected for analysis. Primary staging procedure was ALND in 799 patients (30.4%) and less invasive procedures (419 SLNB, 1399 TAD, 15 TLNB) in 1,833 (69.6%). Nodal complete pathological response was reported in 1,345 patients (51.1%): 423 (31.4%) after ALND and 922 (68.6%) after TAD/SLNB/TLNB. 2489 patients (94.6%) received post-NACT nodal radiotherapy: 759 (95.0%) after ALND and 1730 (94.4%) after TAD/SLNB/TLNB. After a median follow-up of 2.0 years (range, 0.01-4.5), 15 axillary recurrences occurred after TAD/SLNB/TLNB and 4 after ALND (4.2 vs 2.5 events/1000 person-years, p=0.351). 3-year ARFS was 99.2% (95% CI 98.2-100.0) after ALND and 98.8% (95% CI 98.1-99.5) after TAD/SLNB/TLNB. For TAD/SLNB/TLNB, the lower bound of a 90% CI was 98.2%. After SLNB, 1 axillary recurrence occurred and 14 after TAD (1.2 vs 5.1 events/1000 person-years, p=0.132). Results were similar upon controlling for clinicopathological risk factors and neoadjuvant treatment or exclusion of 143 patients without radiotherapy. iBCSS at 3 years was 85.7% (95% CI 82.6-89.0) for ALND and 88.2% (95% CI 86.0-90.3) for TAD/SLNB/TLNB. Conclusion In patients who convert from clinically node-positive to node-negative breast cancer, the AXSANA study showed that less invasive surgical staging procedures are associated with a low axillary recurrence rate, not inferior to ALND after 3 years, regardless of initial tumor stage or subtype. These findings reinforce efforts to minimize surgical morbidity without compromising oncologic outcomes. Citation Format: T. Kühn, M. Banys-Paluchowski, N. Ditsch, E. Stickeler, M. Hauptmann, J. Schroth, G. Karadeniz Cakmak, M. Hahn, M. Thill, T. Reimer, S. Fröhlich, E. Schmidt, M. Lux, H. Kolberg, I. Rubio, M. Gasparri, M. Kontos, E. Bonci, L. Niinikoski, D. Murawa, D. Pinto, F. Peintinger, E. Schlichting, H. Nina, H. Valiyeva, M. Vanhoeij, L. Rebaza, B. Aktas Sezen, K. Jursik, G. Kadayaprath, L. Dostalek, A. Kothari, A. Perhavec, T. Ivanov, D. Zippel, S. Thongvitokomarn, B. Adamczyk, M. Gurleyik, D. Watermann, M. Porpiglia, S. Grasshoff, S. Loibl, D. Krug, A. Lebeau, R. Di Micco, O. Gentilini, J. de Boniface, S. Hartmann, AXSANA study group.. More versus less invasive axillary surgical staging procedures in breast cancer patients converting from a clinically node-positive to a clinically node-negative stage through neoadjuvant chemotherapy - primary endpoint analysis of the international prospective multicenter AXSANA/EUBREAST 3(R)study [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 GS2-01.