No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy (Neo-NAUTILUS)

January 26, 2026 updated by: Wonshik Han, Seoul National University Hospital

No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy: A Prospective, Phase III Clinical Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

464

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Wonshik Han, MD, PhD.
  • Phone Number: 82-2-3461-6060
  • Email: hanw@snu.ac.kr

Study Locations

  • South Korea
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Hopsital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Women aged ≥19 years.
  • Histologically confirmed invasive breast carcinoma treated with neoadjuvant chemotherapy.
  • 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- and post-NAC MRI).
  • Negative axillary lymph node status on ultrasound after NAC.
  • Planned for breast-conserving surgery with completed neoadjuvant chemotherapy (at least half the planned regimen must be completed).
  • ECOG performance status of 0-2.
  • Signed written informed consent before enrollment.

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: No SLNB group
The study arm - BCS without SLNB
Procedure: No axillary surgery
BCS only. Ommission of axillary surgery. No axillary surgery after neoadjuvant chemotherapy.
Other: SLNB group
The control arm - BCS with SLNB(+/-ALND)
Procedure: Axillary surgery
BCS with SLNB(+/-ALND)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Invasive Disease Free Survival (iDFS)
Time Frame: 5 years
Evaluate invasive disease free survivals
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 5 years
Evaluate overall survival
5 years
Distant Metastasis Free Survival (DMFS)
Time Frame: 5 years
Evaluate distant metastasis free survival
5 years
Axillary recurrence rate
Time Frame: 5 years
Evaluate ipsilateral axillary recurrence rate
5 years
Locoregional Recurrence Rate (LRR)
Time Frame: 5 years
Evaluate locoregional recurrence rate
5 years
QoL
Time Frame: 1 year
Evaluate Quality of Life of patient by EORTC QLQ-C30 questionnaire
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Collaborators

Asan Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 4, 2025

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2034

Study Registration Dates

First Submitted

November 21, 2024

First Submitted That Met QC Criteria

November 21, 2024

First Posted (Actual)

November 26, 2024

Study Record Updates

Last Update Posted (Actual)

January 28, 2026

Last Update Submitted That Met QC Criteria

January 26, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-2410-138-1581

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study protocol will be shared.

IPD Sharing Time Frame

The study protocol will be published as a journal article.

IPD Sharing Access Criteria

Anyone interested in viewing the study protocol will be able to access it through the published journal.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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