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

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.