Occult Axillary Node Metastases in Breast Cancer Are Prognostically Significant: Results in 368 Node-Negative Patients With 20-Year Follow-Up

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Abstract
Purpose: In breast cancer, sentinel lymph node (SLN) biopsy allows the routine performance of serial sections and/or immunohistochemical (IHC) staining to detect occult metastases missed by conventional techniques. However, there is no consensus regarding the optimal method for pathologic examination of SLN, or the prognostic significance of SLN micrometastases. Patients and Methods: In 368 patients with axillary node-negative invasive breast cancer, treated between 1976 and 1978 by mastectomy, axillary dissection, and no systemic therapy, we reexamined the axillary tissue blocks following our current pathologic protocol for SLN. Occult lymph node metastases were categorized by pattern of staining (immunohistochemically positive or negative [IHC±], hematoxylin-eosin staining positive or negative [H & E ±]), number of positive nodes (0, 1, > 1), number of metastatic cells (0, 1 to 20, 21 to 100, > 100), and largest cluster size (≤ 0.2 mm [pN0i+], 0.3 to 2.0 mm [pN1mi], > 2.0 mm [pN1a]). We report 20-year results as overall survival (OS), disease-free survival (DFS), and disease-specific death (DSD). Results: A total of 23% of patients (83 of 368) were converted to node-positive. Of these, 73% were ≤ 0.2 mm in size (pN0i+), 20% were 0.3 to 2.0 mm (pN1mi), and 6% were more than 2 mm (pN1a). On univariate and multivariate analysis, pattern of staining, number of positive nodes, number of metastatic cells, and cluster size were all significantly related to both DFS and DSD. On multivariate analysis, each of these measures had significance comparable to, or greater than, tumor size, grade or lymphovascular invasion. Conclusion: In breast cancer patients staged node-negative by conventional single-section pathology, occult axillary node metastases detected by our current pathologic protocol for SLN are prognostically significant.