Purpose: Sentinel lymph node biopsy (SLNB) is the standard axillary staging procedure for clinically node-negative early breast cancer, but is associated with morbidity.1,2 The SOUND and INSEMA trials demonstrated the safety of omitting SLNB in carefully selected patients3,4. This study aimed to assess the real-world impact of applying SOUND and INSEMA eligibility criteria to a large Australian breast cancer cohort, specifically quantifying the proportion of sentinel lymph node (SLN) positivity that would have been missed. Methods: A retrospective cohort study was conducted using BreastSurgANZ Quality Audit database from 2009–2023. Female patients with cT1–T2N0 invasive breast cancer who underwent SLNB were included. Patients were retrospectively assessed for eligibility against SOUND and INSEMA criteria. SLN histopathology was compared with trial eligibility to determine missed nodal positivity. Diagnostic accuracy metrics were calculated and clinico-pathological predictors of missed SLN positivity were analysed. Results: A total of 109,877 patients met inclusion criteria. When SOUND criteria were applied, 9.2% (n=5626) of SLN-positive cases would have been omitted from SLNB, compared with 11.8% (n=9304) under INSEMA criteria. The negative predictive value was 83.2% for SOUND and 85.0% for INSEMA. Missed nodal disease rates were higher in HER 2 enriched or grade 2-3 cancers under both trial criteria. Conclusion: Application of SOUND and INSEMA criteria to a real-world Australian cohort would result in omission of SLNB in a small but measurable proportion of SLN-positive patients. These findings support careful patient selection and highlight the importance of tumour biology and imaging quality when considering axillary de-escalation outside clinical trials. References: 1. Krag DN et al. Lancet Oncol. 2010. 2. Veronesi U et al. N Engl J Med. 2003. 3. Gentilini O et al. Lancet Oncol. 2023. 4. Kühn T et al. Lancet Oncol. 2023.