Prognostic significance of occult lymph node metastases in node-negative breast cancer

Background: Lymph node status, established by a single hematoxylin and eosin (H&;E) section from each node, remains an important prognostic indicator in patients with breast cancer, but used alone it is insufficient to identify patients who will develop metastatic disease. This study was conducted to assess the significance of detecting occult metastases in 86 patients with breast cancer originally reported to be histologically node negative. None of the patients received adjuvant systemic therapy. Methods: Five additional levels from formalin-fixed, paraffin-embedded nodes were examined at 150-µm intervals with H&;E staining and a cocktail of antikeratin antibodies (AE1/AE3) recognizing low molecular weight acidic keratins. Results: Nodes from 11 (12.8%) of 86 patients contained occult metastases. All metastases identified by cytokeratin antibody were also detected in H&;E-stained sections. With median follow-up of 80 months, distant metastases occurred in five of 11 occult node-positive patients (45%) and 13 of 75 patients whose nodes were negative on review (17%). Median time to recurrence was 89 months for occult node-positive patients and not yet reached for node-negative patients (p=0.048). The disease-specific 5-year survival rate was 90% for occult node-positive patients and 95% for node-negative patients. Conclusions: The presence of occult metastases shortened the disease-free interval and suggested that more diligent axillary staging would more accurately identify patients who would benefit from systemic adjuvant treatment.