A randomized trial of sentinel node biopsy omission after neoadjuvant systemic therapy in clinically node-negative or selected node-positive breast cancer.

Abstract

TPS651 Background: Omission of axillary surgery has been established as a safe option in selected patients with early-stage breast cancer undergoing upfront surgery. In the neoadjuvant systemic therapy (NST) setting, however, axillary surgery remains standard practice. Ongoing trials, including EUBREAST-01, ASICS, and ASLAN, are evaluating the safety of omitting sentinel lymph node biopsy (SLNB) after NST, but these studies have largely been limited to single-arm designs and to patients with confirmed breast pathologic complete response (pCR). Retrospective studies suggest that axillary nodal clearance after NST may be predicted using tumor subtype, treatment response, and post-NST imaging, independent of breast pCR. The NeoNAUTILUS trial was designed to prospectively evaluate the safety of omitting SLNB after NST in patients predicted to have no residual axillary disease, using axillary response–based selection rather than breast pCR. Methods: NeoNAUTILUS is a prospective, multicenter, randomized, controlled, non-inferiority trial being conducted at 23 centers in Korea. Eligible participants are women aged ≥20 years with clinical T1–T3 invasive breast cancer who have completed NST and are candidates for breast-conserving surgery (BCS). Patients with clinical N0 disease of any subtype are eligible. Selected patients with clinical N1 disease are eligible if they have HER2-positive, triple-negative, or estrogen receptor–low-positive tumors and demonstrate a >30% reduction in primary tumor size on post-NST magnetic resonance imaging. All participants must have no suspicious lymph nodes on post-NST axillary ultrasound. Participants are randomized 1:1 to BCS with SLNB or BCS without axillary surgery, stratified by clinical nodal status (cN0 vs cN1) and tumor subtype. Patients remain blinded to treatment allocation until surgery. Whole-breast irradiation is planned for all patients, with protocol-defined axillary radiation fields in the no-SLNB group according to initial nodal status. The primary endpoint is 5-year invasive disease-free survival. Secondary endpoints include overall survival, distant metastasis-free survival, ipsilateral axillary recurrence, locoregional recurrence, and patient-reported quality of life. A total of 464 patients are planned for enrollment over 3 years with a minimum follow-up of 5 years. Enrollment began in May 2025 and is ongoing. Clinical trial registration: NCT06704945; KCT0010174. Clinical trial information: NCT06704945 .