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

Seoul National University

Status and phase: Not yet enrolling; Phase 3

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

Treatments: Procedure: No axillary surgery; Procedure: Axillary surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT06704945

H-2410-138-1581

Details and patient eligibility

About

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.

Full 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.

Enrollment: 464 estimated patients

Sex: Female

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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464 participants in 2 patient groups

No SLNB group

Experimental group

Description:

The study arm - BCS without SLNB

Treatment:

Procedure: No axillary surgery

SLNB group

Other group

Description:

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

Treatment:

Procedure: Axillary surgery