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NCT Number: NCT07841704

NAUTILUS-04: No Axillary Surgical Treatment in Low-Risk Clinically Node-Negative Breast Cancer Without Whole-Breast Radiotherapy - A Prospective, Randomized, Phase III, Non-inferiority Clinical Trial

The safety of omitting sentinel lymph node biopsy (SLNB) has been established only in patients undergoing breast-conserving surgery with whole-breast radiotherapy, as demonstrated in the prior randomized trials. Whether SLNB can be omitted in patients who will not receive whole-breast radiotherapy remains unknown, despite the parallel expansion of radiotherapy de-escalation in low-risk populations.

NAUTILUS-04 is a prospective, multicenter, randomized, phase III non-inferiority trial evaluating the oncologic safety of SLNB omission in postmenopausal patients with low-risk, clinically node-negative breast cancer who are not planned to receive whole-breast radiotherapy.

Eligible patients are postmenopausal women aged 55 years or older with estrogen receptor-positive, HER2-negative invasive breast cancer, clinical T1-2 and clinically node-negative disease confirmed by physical examination and axillary ultrasound, without neoadjuvant systemic therapy. Patients must be planned for one of three local treatments: breast-conserving surgery without radiotherapy, breast-conserving surgery with accelerated partial breast irradiation, or mastectomy without radiotherapy.

A total of 1,520 patients will be randomized 1:1 to SLNB or no axillary surgery, stratified by planned breast surgery (breast-conserving surgery versus mastectomy) and age (55-64 versus 65 years or older). The primary endpoint is 5-year invasive disease-free survival. Secondary endpoints include 5-year axillary recurrence-free survival, distant recurrence-free survival, overall survival, and quality of life assessed by the EORTC QLQ questionnaire.

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Key information

Conditions

Breast Cancer (Early Breast Cancer) Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Sentinel Lymph Node Biopsy Skin Diseases Skin and Connective Tissue Diseases

Age range

55 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Seoul National University Hospital

Seoul, 03080, South Korea

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Postmenopausal women aged 55 years or older
  • Histologically confirmed invasive breast cancer
  • Estrogen receptor-positive and HER2-negative
  • Clinical T1-2
  • Clinically node-negative by physical examination and axillary ultrasound
  • No neoadjuvant systemic therapy
  • Not planned to receive whole-breast radiotherapy
  • Planned for one of the following local treatments:
  • Cohort 1: Breast-conserving surgery without radiotherapy
  • Age under 65 years with clinical T1 tumor and biologically low risk, defined as Oncotype DX Recurrence Score 18 or less, OncoFREE Decision Index 15 or less, or Ki-67 13.25% or less with histologic grade 1 or 2
  • Age 65 years or older with clinical tumor size 3 cm or less and histologic grade 1 or 2
  • Cohort 2: Breast-conserving surgery with accelerated partial breast irradiation, with clinical T1 tumor and histologic grade 1 or 2
  • Cohort 3: Mastectomy without radiotherapy, with histologic grade 1 or 2
  • Written informed consent

Exclusion criteria

  • Clinically or radiologically suspicious axillary lymph nodes
  • Prior ipsilateral invasive breast cancer or prior axillary surgery
  • Bilateral breast cancer
  • Inflammatory breast cancer
  • Pregnancy
  • Any condition that precludes protocol-specified surgery or follow-up
  • Concurrent participation in another interventional clinical trial that may affect the primary endpoint of this study

Treatment and study plan

Omission of axillary surgery

Procedure

Planned breast surgery is performed without any axillary surgical procedure. Neither sentinel lymph node biopsy nor axillary lymph node dissection is performed. Adjuvant treatment decisions are made without pathologic nodal information

Sentinel Lymph Node Biopsy

Procedure

Sentinel lymph node biopsy is performed at the time of planned breast surgery. Subsequent axillary management and adjuvant treatment decisions follow institutional standard practice based on the pathologic nodal findings.

Primary outcomes

  1. Invasive disease free survival

    Time frame: 5 years after randomization

    Invasive disease-free survival is defined as the time from randomization to the first occurrence of invasive ipsilateral breast tumor recurrence, local or regional invasive recurrence, distant recurrence, contralateral invasive breast cancer, second primary invasive cancer, or death from any cause, according to the STEEP criteria.

Secondary outcomes

  1. Overall survival

    Time frame: 5 years from randomization

    Description: Overall survival is defined as the time from randomization to death from any cause.

  2. Distant disease-free survival

    Time frame: 5 years from randomization

    Distant disease-free survival is defined as the time from randomization to the first occurrence of distant recurrence or death from any cause, according to the STEEP criteria.

  3. Axillary recurrence

    Time frame: 5 years from randomization

    Axillary recurrence is defined as histologically or cytologically confirmed recurrence in the ipsilateral axillary lymph nodes, occurring as a first event or concurrently with other recurrence sites.

  4. Health-related quality of life

    Time frame: Before surgery, and 1 and 2 years after surgery

    Health-related quality of life assessed by the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires.

Interested in participating?

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Sponsors and collaborators

Lead sponsor

Wonshik Han

Other

Registry information

Official study title

No Axillary Surgical Treatment in Low-Risk Clinically Node-Negative Breast Cancer Without Whole-Breast Radiotherapy

Acronym: NAUTILUS-04

Important dates

Study start
2026
Primary completion
2034
Study completion
2034
First posted
Sep 25, 2026
Registry last updated
Sep 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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