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.

Sex

Female

Minimum age

55 Years

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