No Axillary sUrgical Treatment In Clinically Lymph Node Negative Patients After UltraSonography

February 11, 2026 updated by: Seoul National University Hospital

No Axillary sUrgical Treatment In Clinically Lymph Node Negative Patients After UltraSonography[NAUTILUS]: A Prospective, Multicenter, Phase III Clinical Trial

NAUTILUS study is a prospective, multicenter, RCT. Clinically T1,T2, node negative BCS candidates with no evidence of metastases in AUS are 1:1 randomized into no SLNB group and SLNB group.

NAUTILUS study aim to establish the minimally invasive treatment of breast cancer by reexamining the necessity of sentinel lymph node biopsy among patients with invasive breast cancer who have tumors under 5cm, are clinically node-negative, and are having breast conserving surgery performed.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

[Background] Skipping ALND, the follow-up treatment in SN-positive patients, has non-inferior oncological outcomes compared to SLNB-only group, given that there is no severe SN metastases.

Axillary ultrasound can effectively exclude high nodal burden, showing 95% NPV in a systematic review.

SLNB has morbidity including lymphedema, limited range of motion, pain, and other post-surgical complications, eventually leading to reduced quality of life.

Considering improvement of imaging modalities and adjuvant care, survival outcome of SLNB must be re-evaluated. Especially research reflective of the regional specificities of Korea and Asia-Pacific is needed.

[Study design] Prospective, Multicenter, RCT.

[Statistical considerations] According to Z0011 trial, 5yr DFS in eligible patients is expected to be 86%, which is between previous data of 88.6% in cT1,2 and SN-negative patients4, and 83.9% in cT1,2 and 1-2 SN-positive patients.

Non-inferiority margin is set at 5%. With 5% significance level and 80% power, 780 patients are needed in each group. Assuming a 10% drop out rate, 1734 patients need to be recruited.

[Screening and Randomization] Participants undergo screening tests that assess eligibility according to inclusion/exclusion criteria.

In order to identify axillary lymph node metastases, axillary ultrasound is first performed by radiologists. Patients showing normal features are enrolled, while for conditionally normal patients, with only 1 suspicion of low nodal burden, axillary lymph node biopsy should be performed. Suspicious patients are excluded under following conditions: patients with 1 or more suspicion of high nodal burden, 2 or more suspicion of low nodal burden, or T2 invasive lobular carcinoma patients with 1 or more low nodal burden. The severity of nodal burden is defined through the criteria.

Patients who underwent radiological axillary staging are randomly assigned (1:1) to the study arm and the control arm before surgical care. Stratification is done based on trial centers and tumor sizes.

[Post-surgical care] All patients are planned to receive ipsilateral whole breast radiation. Patients randomized to non-SLNB arm are recommended to follow high tangential radiotherapy protocol, in which upper margin of radiation field includes axillary level I and II or lies within 2CM from humeral head.

Additional treatment may be performed if deemed necessary by the researcher

[Objectives]

  1. Primary objective

    - 5yr Disease Free Survival

  2. Secondary objectives

    • 5yr Overall Survival
    • 5yr Distant Metastasis Free Survival
    • Axillary recurrence rate
    • Patient reported AE
    • QoL

Study Type

Interventional

Enrollment (Actual)

1734

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • South Korea
    • Seoul
      • Seoul, Seoul, South Korea, 03080
        • Seoul National University Hospital

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

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Women ≥ 19 years
  • Invasive unilateral breast carcinoma with histological confirmation
  • History of invasive breast cancer
  • Histologically or radiologically no suspicion of distant metastases
  • Performance status corresponding to ECOG grade 0-2
  • Tumor size clinically and radiologically ≤ 5cm, independent of hormone receptor and HER2 status
  • Clinically and sonographically negative axillary lymph nodes before biopsy; core needle biopsy or fine needle aspiration of suspicious lymph node required
  • BCS candidate with postoperative whole-breast irradiation and adequate systemic therapy
  • No psychological and geographical restriction in follow-up
  • Written informed consent

Exclusion Criteria:

  • History of any cancer in the previous 5 years
  • Bilateral breast cancer
  • Invasive breast cancer treated with neoadjuvant therapy
  • Tumor size clinically and radiologically > 5cm
  • Mastectomy candidate
  • Pregnancy and breastfeeding
  • Male breast cancer
  • Unable to understand and fill out 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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: No SLNB group
The study arm - BCS without SLNB
Procedure: No SLNB
BCS only. Ommission of SLNB by axilla ultrasonography among selective breast cancer patients
Other: SLNB group
The Control Arm - BCS with SLNB(+/-ALND)
Procedure: SLNB
BCS with SLNB(+/-ALND)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free Survival (DFS)
Time Frame: 5 years
Evaluate 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
Patient reported Adverse Events (AEs)
Time Frame: 1 year
Evaluate Patient reported Adverse Events
1 year
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

National Evidence-Based Healthcare Collaborating Agency

Investigators

  • Principal Investigator: Wonshik Han, Seoul National University Hospital

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)

September 15, 2020

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

March 8, 2020

First Submitted That Met QC Criteria

March 10, 2020

First Posted (Actual)

March 11, 2020

Study Record Updates

Last Update Posted (Actual)

February 13, 2026

Last Update Submitted That Met QC Criteria

February 11, 2026

Last Verified

September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NAUTILUS study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

Subscribe