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Originally published as JCO Early Release 10.1200/JCO.2009.23.2421 on July 20 2009 © 2009 American Society of Clinical Oncology.
Reply to K.M. Musallam et alUniversitair Ziekenhuis Brussel, Brussels, Belgium; and Radiation Oncology, University Hospitals of Geneva, Geneva, Switzerland
Department of Community Occupational and Family Medicine, National University of Singapore, Singapore
Senology and Surgical Gynecologic Oncology Unit, University Hospitals of Geneva, Geneva, Switzerland
Geneva Cancer Registry, Institute for Social and Preventive Medicine, Geneva University, Geneva, Switzerland We thank Musallam et al1 for the thoughtful comments. In our database, the numbers of nodes for patients receiving neoadjuvant therapy are coded separately in keeping with the American Joint Committee on Cancer/International Union Against Cancer's recommendations (distinct "y" prefixed ypN classification after neoadjuvant therapy, as opposed to the general pN classification).2,3 By selecting patients based on the general pN information, neoadjuvant cases were indeed excluded. We are reminded of Baslaim et al's4 study which found that adjuvant systemic treatment may modify the nodal yield in an axillary dissection. Rather than detracting from the strengths of our study, this observation highlights that neoadjuvant therapy is another cause of variability affecting the pN staging, reinforcing our argument for the use of nodal ratios. The importance of nodal ratios in the neoadjuvant setting has most recently been shown by Keam et al5 who found that relapse-free survival (RFS) and overall survival (OS) were not different according to the absolute number of involved nodes, whereas the nodal ratio was an independent prognostic factor for RFS and OS. Keam et al's RFS hazard ratio for the lymph node ratio in a multivariate Cox model was 4.246, which is very close to our breast cancer specific mortality hazard ratio of 4.51.6 We acknowledge the changing patterns of hematoxylin-eosin staining and immunohistochemistry-based assessments. But again, rather than detracting from our study, this argues that nodal ratios are more robust than the pN against such changes. We are naturally aware of the importance of HER2 expression, which was not routinely assessed until recently, and of the importance of hormone receptors. We have focused on hormone receptors and endocrine therapy in a separate study.7 Adding hormone receptors status to our models introduced only minor changes in the values of the hazard ratios (Table 1). The overlap of the confidence intervals of the pN groups did not improve, whereas the clear separation between the confidence intervals of the lymph node ratio groups was maintained (Table 2).
We are grateful for the opportunity of the clarifications and updates. The most recent literature in the neoadjuvant setting and the robustness of the lymph node ratio in different models add to the evidence previously reviewed,8 providing further arguments that the lymph node ratio should be considered as an alternative to the pN staging. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Musallam KM, Jamali FR, Hatoum HA, et al: Axillary lymph node ratio revisited. J Clin Oncol 27:e67; 2009. 2. Greene FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Handbook, 6th Edition New York, NY: Springer Verlag, 2002. p.12–13. 3. Sobin LH, and Wittekind CH. TNM Classification of Malignant Tumours, ed 6 New York, NY: Wiley, 2002. p.13–14. 4. 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] 5. Keam B, Im SA, Kim HJ, et al: Clinical significance of axillary nodal ratio in stage II/III breast cancer treated with neoadjuvant chemotherapy. Breast Cancer Res Treat 116:153–160, 2009.[CrossRef][Medline] 6. 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. 7. Merglen A, Verkooijen HM, Fioretta G, et al: Hormonal therapy for oestrogen receptor-negative breast cancer is associated with higher disease-specific mortality. Ann Oncol 20:857–861, 2009. 8. Woodward WA, Vinh-Hung V, Ueno NT, et al: Prognostic value of nodal ratios in node-positive breast cancer. J Clin Oncol 24:2910–2916, 2006.
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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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