Abstract PS5-08-22: Patients with breast cancer and axillary involvement undergoing Sentinel LYMph Node Biopsy versus Targeted AXillary Dissection after primary systemic treatment: which axillary staging saves more lymphnodes? A registry-based randomized controlled trial (SLYMT-AXSANA EUBREAST 3R)

Abstract Background: Most patients with breast cancer and axillary nodal involvement achieve a clinical and radiological response after primary systemic treatment (PST). In this case, a surgical axillary de-escalation should be offered to reduce surgical trauma and subsequent morbidity. Sentinel lymph node biopsy (SLNB) (with a dual tracer and/or removal of at least 3 sentinel lymph nodes) or targeted axillary dissection (TAD) can safely replace axillary lymphadenectomy. The more axillary lymph nodes removed, the higher the morbidity. Therefore, SLNB and TAD represent surgical de-escalation procedures with lower body impact and arm injury compared to full axillary lymphadenectomy. Retrospective studies observed no difference in oncological outcome between SLNB and TAD. Follow-up data from the current ongoing prospective registry AXSANA (EUBREAST 3) will provide unique real-world evidence on this topic. In the meantime, surgical axillary staging is characterized by a lack of standardization and a wide heterogeneity between countries, institutions, and guidelines. The choice of treatment is therefore determined by preferences of institutions and/or surgeons rather than benefits for the patients. Currently, there is no consensus on whether SLNB or TAD minimizes the number of lymph nodes removed. No randomized clinical trials have compared SLNB versus TAD in node positive breast cancer patients converting to node negative after PST. The aim of the current study (SLYMT-AXSANA, EUBREAST 3R) is to use a pragmatic design and conduct, to our knowledge, the first registry-based randomized controlled trial in this setting. We will compare the number of lymph nodes removed during SLNB versus TAD and related morbidity in patients with breast cancer who initially present with clinically node-positive status and convert to clinical node-negative after receiving PST. The number of additional nodes included, the failure of techniques, and the need for subsequent axillary lymphadenectomy according to the results of the frozen section during SLNB versus TAD will be assessed in order to better define both techniques. Methodology: Following similar inclusion and exclusion criteria of the AXSANA(EUBREAST 3) study (cT1-4, cN+, M0 breast cancer patients undergoing PST), eligible patients will be randomized to SLNB versus TAD, prior to PST. The biopsy of the metastatic lymph node/s and the marking of the positive lymph node(s) will be required, regardless of the arm of the study. Only patients achieving complete clinical and radiological axillary response will be included in the analysis. Data will be prospectively collected in RedCap. Patient-reported outcome measures (PROMS) will be collected at a predefined time. Sample size calculation: For 80% power to detect whether the number of removed lymph nodes differs between SLNB and TAD (type 1 error=5%), a sample size of 170 patients per group (340 in total) would be required if the number of lymph nodes removed after TAD is 15% lower than after SLNB (ratio=0.85), i.e., assuming 2.72 removed lymph nodes after TAD and 3.2 after SLNB (according to preliminary data from the AXSANA(EUBREAST-3) registry on 4,336 patients from 284 study sites and 26 countries). The calculation is based on a test for the ratio of two Poisson rates, and parameters mean=3.2 and variance=2.7 of the Poisson distribution for SLNB were calculated from the AXSANA (EUBREAST 3). Citation Format: M. Gasparri, S. Hartmann, M. Hauptmann, M. Banys-Paluchowski, N. Ditsch, R. Di Micco, O. Gentilini, T. Kuehn. Patients with breast cancer and axillary involvement undergoing Sentinel LYMph Node Biopsy versus Targeted AXillary Dissection after primary systemic treatment: which axillary staging saves more lymphnodes? A registry-based randomized controlled trial (SLYMT-AXSANA EUBREAST 3R) [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 PS5-08-22.