Skipping axillary surgery when lymph nodes look normal on ultrasound after preoperative chemotherapy

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

Phase 3 Interventional Seoul National University Hospital · NCT06704945

This trial tests whether skipping axillary lymph node surgery after neoadjuvant chemotherapy is safe for breast cancer patients whose lymph nodes look normal on ultrasound.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment464 (estimated)
Ages19 Years and up
SexFemale
SponsorSeoul National University Hospital Academic / other
Drugs / interventionschemotherapy, radiation
Locations1 site (Seoul)
Trial IDNCT06704945 on ClinicalTrials.gov

What this trial studies

NEO-NAUTILUS is a prospective, multicenter, randomized phase III non-inferiority trial comparing omission of axillary lymph node surgery to sentinel lymph node biopsy in patients who are clinically node-negative on ultrasound after neoadjuvant chemotherapy. Participants who completed at least part of a planned NAC regimen and are planned for breast-conserving surgery are randomized to either no axillary surgery or standard sentinel node surgery. The primary endpoint is 5-year disease-free survival, with follow-up to detect recurrences and survival differences between arms. The trial builds on prior de-escalation work (e.g., SOUND, Z0011) and uses contemporary imaging and pathological response data to select patients.

Who should consider this trial

Good fit: Women age 19 or older with invasive breast cancer who completed neoadjuvant chemotherapy, are clinically node-negative on post‑chemotherapy axillary ultrasound, and are scheduled for breast-conserving surgery with ECOG 0–2 may be eligible.

Not a fit: Patients who need mastectomy, have persistently positive axillary ultrasound, tumor size >5 cm after chemotherapy, bilateral disease, recent other cancers, or are pregnant/breastfeeding are unlikely to benefit from omitting axillary surgery in this protocol.

Why it matters

Potential benefit: If successful, patients could avoid axillary surgery and its complications (like lymphedema and sensory loss) without reducing their chance of remaining cancer-free over five years.

How similar studies have performed: Previous randomized and single-arm studies (e.g., ACOSOG Z0011, NSABP B‑32, SOUND and several post‑NAC single-arm cohorts) support safe omission of axillary surgery in selected patients, but randomized phase III data specifically after neoadjuvant chemotherapy have been limited until now.

Eligibility criteria

Show full inclusion / exclusion 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.

Where this trial is running

Seoul

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Breast CancerNeoadjuvant TherapySentinel Lymph Node BiopsyOmission of axillary surgery after neoadjuvant chemotherapyBreast cancerNeoadjuvant chemotherapyDe-escalationOmission of surgery
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.