Simple SummaryFollowing neoadjuvant systemic therapy (NAST), patients who were clinically node-negative at diagnosis still routinely undergo sentinel lymph node biopsy (SLNB) to detect nodal disease. Surgical staging of the axilla is currently the standard of care, including for those who achieve complete imaging response in the breast and/or axilla. It has been well established that certain breast cancer subtypes respond better to NAST and are more likely to achieve pathological node-negative status (ypN0). These complete responses are underpinned by advances in systemic therapy and subtype-specific targeted treatment. Our pooled analysis shows that patients with no clinical evidence of axillary node involvement at diagnosis, who respond well to upfront systemic therapy, have around 2% chance of disease in sentinel lymph nodes. This suggests that where the risk of nodal disease is sufficiently low, there is a possibility of safely omitting axillary surgery in selected patients.AbstractRecent advances in systemic treatment for breast cancer have been underpinned by recognising and exploiting subtype-specific vulnerabilities to achieve higher rates of pathologic complete response (pCR) after neo-adjuvant systemic therapy (NAST). This down-staging of disease has permitted safe surgical de-escalation in patients who respond well. Triple-negative (TNBC) or HER2-positive breast cancer is most likely to achieve complete radiological response (rCR) and pCR after NAST. Hence, for selected patients, particularly those who are clinically node-negative (cN0) at diagnosis, the probability of disease in the sentinel node after NAST could be low enough to justify omitting axillary surgery. The aim of this pooled analysis was to determine the rate of sentinel node positivity (ypN+) in patients with TNBC or HER2-positive breast cancer who were initially cN0, achieving rCR and/or pCR in the breast after NAST. MedLine was searched using appropriate search terms. Five studies (N = 3834) were included in the pooled analysis, yielding a pooled ypN+ rate of 2.16% (95% CI: 1.70–2.63). This is significantly lower than the acceptable false negative rate of sentinel lymph node biopsy (SLNB) and supports consideration of omission of SLNB in this subset of patients.