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

NCT ID: NCT06704945

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 464 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-04
• Study Completion Date: 2034-12-31

Brief 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.

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.

Conditions

Breast Cancer; Neoadjuvant Therapy; Sentinel Lymph Node Biopsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

No SLNB group

The study arm - BCS without SLNB

Group Type: EXPERIMENTAL

No axillary surgery

Intervention Type: PROCEDURE

BCS only. Ommission of axillary surgery. No axillary surgery after neoadjuvant chemotherapy.

SLNB group

The control arm - BCS with SLNB(+/-ALND)

Group Type: OTHER

Axillary surgery

Intervention Type: PROCEDURE

BCS with SLNB(+/-ALND)

Interventions

No axillary surgery

BCS only. Ommission of axillary surgery. No axillary surgery after neoadjuvant chemotherapy.

Intervention Type: PROCEDURE

Axillary surgery

BCS with SLNB(+/-ALND)

Intervention Type: PROCEDURE

Eligibility Criteria

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.

• Minimum Eligible Age: 19 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Asan Medical Center

OTHER

Sponsor Role: collaborator

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Wonshik Han

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Seoul National University Hopsital

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Wonshik Han, MD, PhD.

Role: CONTACT

hanw@snu.ac.kr

82-2-3461-6060

References

Jung JG, Ahn SH, Lee S, Kim EK, Ryu JM, Park S, Lim W, Jung YS, Chung IY, Jeong J, Chang JH, Shin KH, Chang JM, Moon WK, Han W. No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial. BMC Cancer. 2022 Feb 20;22(1):189. doi: 10.1186/s12885-022-09273-1.

Reference Type: BACKGROUND

PMID: 35184724 (View on PubMed)

Jung JJ, Kim HJ, Chae BJ, Kim EK, Ahn JH, Jeong J, Lee S, Jung SP, Woo J, Min J, Cheun JH, Chung MS, Shin KH, Chang JM, Moon WK, Han W. A Randomized Trial of Sentinel Node Biopsy Omission After Neoadjuvant Systemic Therapy in Clinically Node-Negative or Selected Node-Positive Breast Cancer. J Breast Cancer. 2025 Nov 14. doi: 10.4048/jbc.2025.0157. Online ahead of print.

Reference Type: DERIVED

PMID: 41311332 (View on PubMed)

Other Identifiers

H-2410-138-1581

Identifier Type: -

Identifier Source: org_study_id