No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy

Last updated: January 26, 2026
Sponsor: Seoul National University Hospital
Overall Status: Active - Recruiting

Phase

3

Condition

Breast Cancer

Cancer

Treatment

No axillary surgery

Axillary surgery

Clinical Study ID

NCT06704945
H-2410-138-1581
  • Ages > 19
  • Female

Study Summary

NEO-NAUTILUS is a prospective, multicenter, randomized phase III clinical trial to evaluate whether omitting axillary lymph node surgery (ALND or SLNB) in clinically lymph node-negative breast cancer patients after neoadjuvant chemotherapy is non-inferior to performing SLNB in terms of 5-year disease-free survival.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Women aged ≥19 years.

  • Histologically confirmed invasive breast carcinoma treated with neoadjuvantchemotherapy.

  • Clinical staging prior to NAC: cT1-3, cN0, M0 (AJCC 8th Edition).

  • If pre-NAC staging is cT1-3, cN1, M0, must meet the following criteria:

  1. HER2-positive or triple-negative breast cancer (TNBC).

  2. At least 30% reduction in tumor size on MRI after NAC (comparing pre- andpost-NAC MRI).

  • Negative axillary lymph node status on ultrasound after NAC.

  • Planned for breast-conserving surgery with completed neoadjuvant chemotherapy (atleast half the planned regimen must be completed).

  • ECOG performance status of 0-2.

  • Signed written informed consent before enrollment.

Exclusion

Exclusion Criteria:

  • History of any cancer within the past 5 years.

  • Bilateral breast cancer.

  • Patients requiring mastectomy.

  • Tumor size >5 cm after NAC.

  • Male breast cancer.

  • Pregnant or breastfeeding women.

  • Inability to understand and complete questionnaires.

Study Design

Total Participants: 464
Treatment Group(s): 2
Primary Treatment: No axillary surgery
Phase: 3
Study Start date:
June 04, 2025
Estimated Completion Date:
December 31, 2034

Study Description

Background:

  • No prospective studies have proven that axillary lymph node surgery improves survival in breast cancer patients.

  • The ACOSOG Z0011 trial showed that additional axillary dissection did not improve recurrence or survival, even with a 23.7% incidence of non-sentinel node metastases.

  • NSABP B-32 established the oncologic safety of SLNB, significantly reducing complications like lymphedema compared to axillary dissection. However, SLNB still carries risks of lymphedema, sensory changes, seromas, and infections.

  • The trend has now shifted toward identifying candidates for omitting axillary surgery to minimize unnecessary complications.

  • The SOUND trial demonstrated non-inferiority of omitting SLNB in early-stage breast cancer patients with negative axillary ultrasound. Five-year distant metastasis-free survival was comparable between SLNB and no-SLNB groups (97.7% vs. 98.0%).

  • Improved ultrasound accuracy (e.g., FNR: 13.7% in SOUND; 11.3% in NAUTILUS) and the therapeutic contribution of whole-breast radiation likely support these findings.

  • Patients with a complete pathological response (pCR) in the breast post-NAC rarely have residual lymph node metastases, reducing the need for axillary surgery.

  • Single-arm studies (e.g., EUBREAST-01, ASICS, ASLAN) have explored omitting axillary surgery in patients with confirmed breast pCR. However, these studies face limitations due to small sample sizes, single-arm design, and the necessity of axillary surgery if pCR is not achieved.

  • To address these limitations, the NEO-NAUTILUS trial proposes the first randomized trial to compare disease-free survival and local recurrence rates between patients who omit SLNB (experimental group) and those who undergo SLNB (control group) after NAC, focusing on patients deemed axillary node-negative by ultrasound.

Connect with a study center

  • Seoul National University Hopsital

    Seoul 1835848, 03080
    South Korea

    Active - Recruiting

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