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Originally published as JCO Early Release 10.1200/JCO.2009.23.0698 on July 20 2009 © 2009 American Society of Clinical Oncology.
Axillary Lymph Node Ratio RevisitedDepartment of Internal Medicine, Division of Hematology & Oncology, American University of Beirut Medical Center, Beirut, Lebanon
Department of Surgery, Division of General Surgery, American University of Beirut Medical Center, Beirut, Lebanon
Department of Internal Medicine, Division of Hematology & Oncology, American University of Beirut Medical Center, Beirut, Lebanon
Department of Obstetrics and Gynecology, American University of Beirut Medical Center, Beirut, Lebanon
Department of Internal Medicine, Division of Hematology & Oncology, American University of Beirut Medical Center, Beirut, Lebanon To the Editor:
We read with interest the article by Vinh-Hung et al1 examining the superiority of the lymph node ratio (LNR) to the absolute number of positive lymph nodes (pN) as a prognostic indicator in patients with lymph node–positive breast cancer. The authors conclude that LNR cut-offs (0.2 and 0.65) provide better patient separation into low, intermediate, and high risk groups than pN. This was mostly evident as patients with pN2 (four to nine positive nodes) and pN3 ( The study did not take into consideration or document if any patients received neoadjuvant chemotherapy. There was no mention in the methodology section if such patients were excluded from the analysis. This is relevant as neoadjuvant systemic treatments may modify the nodal yield in an axillary dissection.2 In other words, patients who were classified as belonging to the pN2 category may truly belong to pN3, and thus, have a similar overall survival to the latter group. Moreover, the authors failed to mention the pathological method used to confirm nodal involvement. During the primary era of the study, it is likely that the majority of cases of micrometastatic disease were diagnosed using hematoxylin-eosin (H&E) staining, rather than immunohistochemistry (IHC) or molecular studies. Most centers have continued to use H&E staining as a minimum standard in nodal assessment. However, contemporary studies examining step sectioning and IHC protocols support the use of serial sectioning and IHC assessment to reduce the risk of false-negative results with H&E histologic examination alone.3–5 Again this may also explain a cross-over in diagnosis and eventually in survival between pN2 and pN3 patients. Lastly, tumor receptor status (estrogen and progesterone) and HER2 overexpression were not included in survival analysis. These variables may not have an established role in overall survival, yet they remain significant predictors of adjuvant treatment response.6 Consequently, since adjuvant treatment was a significant predictor of survival on multivariate analysis in Vinh-Hung et al's study,1 a confounding effect of tumor receptor status on overall survival cannot be ruled out. The statistical superiority of LNR, as a global variable, to pN is so far well documented. This may offer a great clinical advantage as it takes into consideration the total number of retrieved nodes, and thus, may help neutralize interinstitutional differences in axillary dissection techniques. The study by Vinh-Hung et al provides a well appreciated contribution by defining LNR cut-offs with significant separation in survival. However, the superiority of the assigned cut-offs to the pN system categories may not be clearly established based on this study. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Vinh-Hung V, Verkooijen HM, Fioretta G, et al: Lymph node ratio as an alternative to pN staging in node-positive breast cancer. J Clin Oncol 27:1062–1068, 2009. 2. Baslaim MM, Al Malik OA, Al Sobhi SS, et al: Decreased axillary lymph node retrieval in patients after neoadjuvant chemotherapy. Am J Surg 184:299–301, 2002.[CrossRef][Medline] 3. Gillanders WE, Mikhitarian K, Hebert R, et al: Molecular detection of micrometastatic breast cancer in histopathologynegative axillary lymph nodes correlates with traditional predictors of prognosis: An interim analysis of a prospective multi-institutional cohort study. Ann Surg 239:828–837, 2004.[CrossRef][Medline] 4. Cserni G, Bianchi S, Boecker W, et al: Improving the reproducibility of diagnosing micrometastases and isolated tumor cells. Cancer 103:358–367, 2005.[CrossRef][Medline] 5. Turner RR, Weaver DL, Cserni G, et al: Nodal stage classification for breast carcinoma: Improving interobserver reproducibility through standardized histologic criteria and image-based training. J Clin Oncol 26:258–263, 2008. 6. Kyndi M, Sørensen FB, Knudsen H, et al: Danish Breast Cancer Cooperative Group: Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: The Danish Breast Cancer Cooperative Group. J Clin Oncol 26:1419–1426, 2008.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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10 positive nodes) involvement showed an imbalance in prognostic separation, with survival curves crossing after 15 years. Although the authors described several limitations to their work, they still failed to mention some very pertinent shortcomings. 
