Non-Inferiority of Survival in Early Breast Cancer Patients with False-Negative Sentinel Nodes After Completing Axillary Lymph Node Dissection

Abstract Background Sentinel lymph node biopsy (SLNB) is standard approach of axillary region for early breast cancer patients with clinically negative node. The present study investigated patients with false-negative sentinel nodes (FNSN) of intraoperative frozen section.Methods A case-control study with 1:3 ratio was conducted. FNSN was diagnosed as negative sentinel nodes (SNs) in frozen sections, but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) blocks. Control was defined no metastasis of SNs in both frozen and FFPE sections.Results Total 20 FNSN cases and 60 matched-controls were enrolled from 333 SLNB patients between April 1, 2005 and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between FNSN and controls. The FNSN patients had a larger tumor size in preoperative mammography and more lymphatic tumor emboli in core biopsy (P-value 0.033 and < 0.001, respectively). Four FNSN patients had metastasis in the non-relevant SNs. Other 16 FNSN patients had results of benign lymphoid hyperplasia of SNs in frozen sections and metastasis in FFPE blocks. Micrometastasis (less than 2 mm) was detected in seven of 16 patients and metastases in non-sentinel nodes was recognized in two of 16 patients. All FNSN patients received second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed recurrence of breast cancer. The disease-free survival, disease-specific survival, and overall survival in FNSN were non-inferior than controls.Conclusion Outcomes of FNSN patients after completing ALND was non-inferior to those without metastasis in SNs. ALND improved survival of patients with metastasis non-sentinel ALNs. However, omitting ALND had no effect for those have only micrometastasis in SNs.