De-escalation of axillary surgery in clinically node-negative (cN0) breast cancer: current evidence, advances, and controversies

Clinically node-negative (cN0) breast cancer accounts for a large proportion of newly diagnosed cases, and its axillary management is undergoing a paradigm shift toward de-escalation aimed at minimizing surgical morbidity. Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for nodal staging in cN0 disease, and subsequent trials have questioned the need for completion ALND in selected SLN-positive patients. This narrative review summarizes two decades of pivotal trial evidence across three conceptually distinct de-escalation strategies, which differ in their levels of evidence. First, phase III randomized evidence supports omission of ALND after a positive SLNB for isolated tumor cells and micrometastases (IBCSG 23-01; 10-year disease-free survival HR 0.85, with the non-inferiority criterion met), and for 1-2 macrometastases when combined with breast-conserving surgery and radiotherapy (ACOSOG Z0011, AMAROS, SENOMAC). Second, omission of SLNB itself has demonstrated 5-year oncological safety in rigorously selected low-risk patients with small tumors and negative preoperative axillary ultrasonography (SOUND, INSEMA), in cohorts that were predominantly HR-positive/HER2-negative. Third, emerging strategies, such as advanced imaging, ctDNA-based monitoring, and AI-assisted diagnostics, may further refine patient selection but remain investigational and are not part of established clinical practice at present. The current evidence is insufficient to support routine de-escalation in HER2-positive and triple-negative disease or in other populations underrepresented in the pivotal trials. Axillary de-escalation is therefore justified only within the specific clinical scenarios validated by randomized trials, and aggressive subtypes and biomarker-guided strategies require further prospective evidence before integration into clinical practice.