Originally published as JCO Early Release 10.1200/JCO.2007.12.6425 on March 10 2008

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

Lee K. Tan, Dilip Giri, Amanda J. Hummer, Katherine S. Panageas, Edi Brogi, Larry Norton, Clifford Hudis, Patrick I. Borgen, Hiram S. Cody, III

From the Department of Pathology; Department of Epidemiology and Biostatistics; Division of Breast Oncology, Department of Medicine; Breast Service, Department of Surgery; and the Memorial Sloan-Kettering Cancer Center, New York, NY

Corresponding author: Hiram S. Cody III, MD, Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; e-mail: codyh{at}mskcc.org

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 [pN0_i+], 0.3 to 2.0 mm [pN1_mi], > 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 (pN0_i+), 20% were 0.3 to 2.0 mm (pN1_mi), 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.

published online ahead of print at www.jco.org on March 10, 2008.

Supported by a grant from the Director's Fund, Evelyn H. Lauder Breast Center.

Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, May 18-21, 2002, Orlando, FL; and Cody HS III, Borgen PI, Tan LK: Ann Surg Oncol 11:227S-230S, 2004.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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