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

Phase 3

Not yet recruiting

• Conditions: Breast Cancer; Neoadjuvant Therapy; Sentinel Lymph Node Biopsy

• Registration Number: NCT06704945
• Lead Sponsor: Seoul National University Hospital

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.

Study Timeline

• Study First Submitted: 2024-11-21
• Study First Submitted QC: 2024-11-21
• Study First Posted: 2024-11-26
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-05
• Last Update Posted: 2025-03-07
• Study Start: 2025-03-31
• Primary Completion: 2029-12-31
• Study Completion: 2034-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 464

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Invasive Disease Free Survival (iDFS)	5 years	Evaluate invasive disease free survivals

Secondary Outcome Measures

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