Abstract: Background and purpose: Sentinel lymph node biopsy (SLNB) is regarded as the standard of care in patients with clinically node-negative (cN₀) disease in early-stage breast cancer, but the timing of SLNB and neoadjuvant chemotherapy (NAC) in cN₀ patients is still controversial. This study aimed to explore the optimal timing of SLNB and NAC, and to assess the feasibility of selective elimination of axillary surgery after NAC in cN₀ patients. Methods: From Oct. 2010 to Apr. 2018, 809 patients who underwent surgery after NAC were included in this retrospective study to analyze the correlation between different clinicopathological characteristics of cN₀ patients and negative axillary lymph node conversion after NAC (ie, ypN₀). Results: Among the 138 cN₀ patients receiving NAC, 81.9% (113/138) were ypN₀. The rates of ypN₀ after NAC in patients with hormone receptor positive (HR+)/ human epidermal growth factor receptor 2 negative (HER2^-), HR⁺/HER2⁺, HR^-/HER2⁺ and triple-negative breast cancer (TNBC) were 75.4% (15/61), 81.0% (17/21), 79.2% (19/24) and 96.9% (31/32), respectively（P<0.001）. The rates of ypN₀ after NAC in patients with HER2⁺ (with targeted therapy) and TNBC were 94.1% (16/17) and 96.9% (31/32), respectively, which were significantly higher than that in HR⁺/HER2^- patients (P<0.05). Molecular subtypes, clinical stage, radiologic complete response and pathologic complete response (bpCR) of the breast tumor correlated with ypN₀ after NAC (with full-course chemotherapy, P<0.05). Molecular subtypes (OR=0.454, P=0.049), clinical stage (OR=3.174, P=0.029) and bpCR (OR=0.337, P=0.016) of the breast tumor were independent predictors for ypN₀ after NAC. Conclusion: The optimal timing of SLNB and NAC in cN₀ patients might be different among different molecular subtypes. It would be preferable to perform SLNB prior to NAC for HR⁺/HER2^- patients, and SLNB after NAC for HER2⁺ (with targeted therapy) and TNBC patients to reduce the risk of axillary lymph node dissection (ALND). In view of the high ypN₀ rate after NAC in cN₀ patients, axillary surgical staging might be selectively eliminated, especially in patients with HER2⁺ (with targeted therapy) and TNBC.

Key words: Breast cancer, Neoadjuvant chemotherapy, Clinically node-negative disease, Sentinel lymph node biopsy