Abstract PS2-05-02: Feasibility of Tailored Axillary Surgery (TAS) in Patients with Clinically Node-Positive Breast Cancer in the Upfront Surgery Setting: Results of a Prospective, Single-Arm, Multicenter Phase II Trial

Abstract Background: Axillary lymph node dissection (ALND), while historically the standard of care for clinically node-positive (cN+) breast cancer, is associated with impaired quality of life and has been progressively de-escalated. In the upfront surgery setting for cN+ disease, ALND remains the standard of care, and evidence supporting its omission is lacking. Tailored axillary surgery (TAS) is a novel approach that targets suspicious nodes while omitting ALND, aiming to reduce morbidity. We conducted a prospective phase II study to assess the feasibility of TAS, ensure procedural consistency, and evaluate associations between clinicopathologic factors and residual tumor burden. Patients and Methods: This single-arm, multicenter phase II trial (jRCTs061220113) was conducted across 42 institutions in Japan within the JCOG Breast Cancer Study Group. TAS was defined as the removal of marked lymph node (LN) with clip, wire, or tattoo, sentinel lymph nodes (SLNs), and palpable LNs, and was followed by completion ALND in accordance with the trial protocol. Eligible patients had invasive breast cancer undergoing upfront surgery, pathologically confirmed axillary metastasis, 1-3 suspicious nodes confined to level I axilla on imaging, and cT1-T3 tumors. The primary endpoint was the proportion of patients with positive non-TAS LNs (non-TAS LN positivity rate). Clinicopathologic factors (cT stage, the number of suspicious nodes on imaging, the number of TAS nodes retrieved, and the number of positive nodes among them) were analyzed using multivariable logistic regression to explore factors associated with non-TAS LN positivity. Secondary endpoints included the retrieval of marked nodes, the TAS identification rate (defined as≥1 metastatic node among TAS nodes), and complications. Results: Between 2023 and 2025, a total of 212 patients were enrolled. The median age was 53.5 years (range, 27-77). Clinical T stage: T1 27.4%, T2 66.0%, T3 6.6%. ER positive in 94.8%, HER2 positive in 3.3%. Histologic grade: G1-2 in 66.0%, G3 in 29.7%. Pathological nodal stage: N1 65.1%, N2 26.4%, N3 8.5%. Pathological stage: IIA 23.6%, IIB 47.6%, IIIA-C 28.8%. Marked node retrieval was achieved in 100% of patients, although 30% of the marked nodes lacked SLN tracer uptake. The median number of TAS nodes retrieved was 4 (IQR, 3-6; range, 1-11), including 2 metastatic nodes (IQR, 1-3). Median number of LNs retrieved by ALND was 18 nodes (IQR 14-24). The identification rate of TAS was 100%. The non-TAS LN positivity rate was 38.7% (82/212). In multivariable analysis, a smaller number of TAS LNs retrieved (OR 0.85; 95% CI 0.73-0.99) and more positive TAS LNs (OR 1.50; 95% CI 1.17-1.94) were associated with higher non-TAS LN positivity, while clinical T stage and number of suspicious nodes on imaging were not significant. The major complications included post-operative bleeding (4.3%) and infection (3.7%). Conclusions: TAS was feasible in cN+ breast cancer undergoing upfront surgery, with acceptable safety. The non-TAS LN positivity rate was slightly higher but comparable to the false-negative rates reported in cN0 SLN-positive trials, while the axillary tumor burden in the present cN+ cohort was higher than that in those trials. These findings support the evaluation of ALND omission as a rational next step, supported by systemic therapy and radiotherapy, and provide the basis for our planned Phase III trial within the framework of stepwise axillary de-escalation. Citation Format: K. Terata, Y. Sagara, S. Yamamoto, T. Sakai, S. Takayama, D. Kitagawa, M. Ogita, N. Sanuki, M. Yoshida, T. Ueno, R. Nakamura, H. Shigematsu, K. Watanabe, H. Bando, A. Yoshimura, T. Onishi, E. Tokunaga, M. Takahashi, T. Hayashi, S. Nishimura, M. Saimura, H. Matsumoto, M. Harao, T. Yoshiyama, T. Sangai, T. Ohtake, H. Tsuda, F. Hara, T. Fujisawa, H. Iwata, T. Shien. Feasibility of Tailored Axillary Surgery (TAS) in Patients with Clinically Node-Positive Breast Cancer in the Upfront Surgery Setting: Results of a Prospective, Single-Arm, Multicenter Phase II Trial 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 PS2-05-02.