Originally published as JCO Early Release 10.1200/JCO.2009.24.0937 on August 31 2009

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Reply to V. Van Belle et al

Universitair Ziekenhuis, Brussel, Belgium, and Radiation Oncology, University Hospitals of Geneva, Geneva, Switzerland

Helena M. Verkooijen

Epidemiology and Public Health, National University of Singapore, Singapore

Gerald Fioretta

Geneva Cancer Registry, Institute for Social and Preventive Medicine, Geneva University, Geneva, Switzerland

Georges Vlastos

Senology and Surgical Gynecologic Oncology Unit, University Hospitals of Geneva, Geneva, Switzerland

Elisabetta Rapiti, Christine Bouchardy

Geneva Cancer Registry, Institute for Social and Preventive Medicine, Geneva University, Geneva, Switzerland

We appreciate Van Belle et al's¹ valuable commenting report. Van Belle et al propose a different value for lymph node ratio (LNR) to estimate disease-free survival based on 686 patients with breast cancer with positive lymph nodes and a short follow-up. We previously demonstrated that in patients with breast cancer, even a 10-year follow-up may not be adequate to evaluate disease-free survival.² Our study was based on 1,829 patients and a mean follow-up of 9 years extending up to 30 years.

Yet, despite these caveats of small number of patients and short follow-up, Van Belle et al¹ show that the LNR is a strong prognosticator with a hazard ratio for disease-free survival of 9.46. Furthermore, they show that the LNR supersedes the number of positive nodes, that categorization of the LNR causes minor loss of efficiency, and, elegantly using time-dependent receiver operating characteristic graphs, they show that the categorized LNR maintains its superiority over the pN classification. Van Belle et al propose 0.10 and 0.40 as the optimal pair of cutoffs for LNR classification, which disagrees with our LNR values of 0.20 and 0.65. Part of the explanation might be the different search procedures. We included a smoothing of the likelihood profiles before computing the minimal difference,³ whereas Van Belle et al did not.

In summary, we are thankful to Van Belle et al for their commenting report which complements Woodward et al's⁴ nodal ratio review with recent and homogeneous data, further establishing the importance of the LNR. However, the issue of optimal cutoffs remains open and will require a multi-institution study in order to reach a consensus.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Van Belle V, Van Calster B, Wildiers H, et al: Lymph node ratio better predicts disease-free survival in node-positive breast cancer than the number of positive lymph nodes. J Clin Oncol 27:e150–e151, 2009.[Free Full Text]

2. Tai P, Yu E, Cserni G, et al: Minimum follow-up time required for the estimation of statistical cure of cancer patients: Verification using data from 42 cancer sites in the SEER database. BMC Cancer 5:48; 2005.[CrossRef][Medline]

3. 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.[Abstract/Free Full Text]

4. 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.[Abstract/Free Full Text]

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