Axillary Surgery in Breast Cancer: Evidence-Based De-escalation Across Upfront and Post-Neoadjuvant Settings Running title: Modern Trends in Axillary Surgery.

This publication is a narrative review of the progressive de-escalation of axillary surgery in breast cancer and synthesizes data from major randomized trials across different levels of nodal disease burden and treatment settings.

Key points:

• Historical shift in axillary management

• Axillary lymph node dissection (ALND) has been largely replaced by sentinel lymph node biopsy (SLNB), significantly reducing lymphedema and shoulder dysfunction without compromising oncologic safety.
• The field is now moving further, questioning the need for SLNB itself in carefully selected patients.

• Evidence by nodal disease burden

• Micrometastases (≤ 2 mm)

• Trials such as IBCSG 23-01 and AATRM showed that omitting ALND in patients with one or more micrometastatic sentinel nodes does not worsen survival or locoregional control.

• Mixed micrometastatic/macrometastatic disease (1–2 positive SLNs)

• ACOSOG Z0011 and AMAROS included patients with 1–2 positive sentinel nodes, irrespective of metastasis size.
• With appropriate systemic therapy and radiotherapy, avoidance of ALND was safe in terms of recurrence and survival.

• Macrometastases (≥ 2 mm; 1–2 positive SLNs)

• Trials such as SENOMAC, SINODAR-ONE, and POSNOC extended de-escalation to patients with 1–2 macrometastatic nodes, again showing that ALND omission is safe when contemporary systemic and radiation therapies are used.

• Omission of SLNB in cN0 disease

• SOUND and INSEMA demonstrated non-inferiority of axillary observation compared with SLNB in clinically node-negative, imaging-negative patients.
• NAUTILUS and similar studies are validating this strategy in Asian populations.

• Neoadjuvant setting

• SLNB is standard for clinically node-negative patients and is feasible in those initially node-positive who convert to clinically node-negative after neoadjuvant chemotherapy.
• Ongoing trials (ASICS, EUBREAST-01, ASLAN) are testing complete omission of axillary surgery in excellent responders, particularly in HER2-positive and triple-negative subtypes, where pathologic complete response rates are high.

• Clinical implications

• The overarching trend is from maximal clearance to biologically and response-adapted optimization of axillary treatment.
• Decisions on axillary surgery should integrate tumor biology, systemic therapy responsiveness, imaging/clinical nodal status, and long-term quality-of-life considerations, rather than defaulting to extensive surgical staging.