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Axillary Lymph Node Nanometastases

These results suggest that even minimal involvement of lymph nodes confers a poor prognosis in breast cancer patients.

One of many dilemmas that oncologists face is determining the prognostic significance of micrometastases or isolated tumor cells that are identified in axillary lymph nodes. An extension of this problem is the potential influence of minute metastases on treatment decisions. In many cases, patients who are defined as axillary node–negative (pN₀) receive recommendations for no adjuvant therapy at all, adjuvant endocrine therapy alone, or adjuvant chemotherapy regimens that are different from those used in confirmed axillary node–positive disease. Previous studies have suggested that minute metastases (nanometastases) detected by immunohistochemistry (IHC), as well as the larger micrometastases identified by hematoxylin and eosin (H&E) staining, have prognostic significance. At present, H&E staining remains the standard for assessing dissected lymph nodes.

To determine whether nanometastases influenced outcomes, researchers retrospectively evaluated a series of 702 consecutive patients who underwent surgery and axillary dissection at a single Italian institution from 1989 through 1993; median follow-up was 8 years. Consistent with treatment standards of the early 1990s, only 8% of the 377 pN₀ patients had been treated with chemotherapy, and 22% had been treated with tamoxifen.

All pN₀ cases were reevaluated by step-sectioning and anticytokeratin IHC analysis. A total of 6676 axillary lymph nodes were restaged, with an average of 250 lymph node sections analyzed per patient; nodes with tumor-cell deposits 0.2 mm in diameter were designated pN_0(i+) nanometastases. After reevaluation, 328 cases (87%) were determined to be pN_0(i-), and cancer cells were revealed in 49 cases (13%): 24 (6.4%) were classified as pN_0(i+) nanometastases (median size, 0.14 mm), and 25 (6.6%) were classified as pN_1mi micrometastases (range, 0.21–2.0 mm). The fraction of pN_0(i+) and pN_0(i-) patients who received adjuvant therapy was similar. Compared with pN_0(i-) patients, pN_0(i+) patients had a hazard ratio for any adverse event of 2.51 (P=0.00019), whereas no significant difference was noted between pN_1mi and pN_0(i+) patients. Metastatic relapse was also significantly more common among pN_0(i+) patients than among pN_0(i-) patients. This unfavorable prognostic effect persisted in multivariate analyses that included tumor grade, pathologic tumor stage, and age.

Comment: These results suggest that even minimal involvement of lymph nodes, nanometastases, confers worse prognoses to patients who would otherwise be considered node–negative. Important caveats regarding this study include that a relatively small number of patients were reclassified as pN_0(i+) (on which conclusions regarding prognosis were based) and that few patients in this series received adjuvant therapy of any kind. Whether contemporary recommendations on the use of adjuvant therapy in node-negative patients would have offset the effect of having pN_0(i+) disease is unknown. Finally, the effort that was expended to analyze these axillary lymph nodes was high — to analyze all dissected nodes in this way on a regular basis would add significant burden to pathologists, and methods would have to be standardized so that a common convention could be used by all institutions.

— William J. Gradishar, MD

Published in Journal Watch Oncology and Hematology December 18, 2006

Citation(s):

Querzoli P et al. Axillary lymph node nanometastases are prognostic factors for disease-free survival and metastatic relapse in breast cancer patients. Clin Cancer Res 2006 Nov 15; 12:6696-701.

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