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LETTERS TO THE EDITOR |
Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
To the Editor:
We read with interest the article titled "Breast Cancer Survival According to Number of Nodes Removed" by Krag and Single.1 The purpose of their study was to determine survival outcome for patients with node-negative and node-positive breast cancer when a variable number of nodes was excised. The data analyzed in this paper are from the Surveillance, Epidemiology, and End Results (SEER) database. In their study, they report that even when all regional lymph nodes were pathologically negative, the number of nodes removed was associated with survival. In the group of patients with breast cancer who had one to three pathologically positive nodes, as with the node-negative group, the higher the number of nodes removed, the greater the survival. These authors concluded that removal of regional nodes is important for the long-term survival even when such nodes are interpreted as pathologically negative. This conclusion could have at least two consequences: the end of sentinel lymph node biopsy and advocacy for extensive lymph node dissection. For the past 20 years, most surgical teams have tried to decrease axillary morbidity with less extensive surgery and sentinel lymph node dissection. This article, therefore, should be cautiously discussed.
Many reports have demonstrated that in patients who are node negative, the number of harvested nodes is correlated with survival. The classic explanation is that the quality of staging is correlated with the number of harvested nodes: patients with fewer nodes removed are less likely to be pathologically node positive and, therefore, to receive adjuvant treatments. For node-positive cases, the Krag and Single study is the first to report the same association between the number of lymph nodes removed and survival. In their discussion, Krag and Single cite a study by van der Wal et al.2 in support of their results for patients who are node positive. In the study of van der Wal et al., a favorable prognosis was found for patients who were node negative with 14 or more removed lymph nodes. For patients with pathologically positive lymph nodes, the total number of lymph nodes removed was also a factor significantly associated with survival, but the outcome was worse for patients who had more nodes removed! For these latter patients, van der Wal et al. introduced a new variable: the lymph node ratio, which proved to be an excellent predictor for survival outcome or development of metastatic disease. Actually, the correlation between the prognosis and the number of lymph nodes may be biased by the relationship between metastatic and uninvolved nodes, which were omitted in the analysis of Krag and Single. Interestingly, Vinh-Hung et al.3 recently reported the survival of the same population (SEER) according to the number of uninvolved nodes and the ratio of involved and uninvolved nodes. They concluded no evidence existed of poor outcome associated with a high number of uninvolved nodes. On the other hand, they found that ratio-based characterization of node involvement was a prognostic factor.
As claimed by Krag and Single, subjective judgments by the surgeons may have had an impact on the extent of surgery and, thus, introduced bias, leading to variable numbers of nodes removed. A comparison of the mean number of nodes removed according to patient and surgicopathologic team characteristics may have helped to identify this bias. Because this analysis is absent in the report of Krag and Single, their results should be interpreted with caution. If no factor is associated with the number of lymph node removed, it can be hypothesized that patient anatomy is the most plausible explanation for the number of lymph nodes removed. The number of uninvolved nodes and the ratio of involved and uninvolved nodes, therefore, are, as is the number of involved nodes, an indication of the tumor burden in the axilla.
The second potential explanation of the results reported by Krag and Single is related to the misclassification of patients with few nodes removed/analyzed. It can be hypothesized that, as admitted for patients who were node negative, nodal metastases are missed (either in the surgical sample or in the axilla) when few nodes are removed/analyzed. If this is the case, the patients with few nodes removed/analyzed may have a higher number of involved nodes than thought and, consequently, have the worse prognosis in their "underestimated" category of nodal involvement.
These two reasons may explain the results reported by Krag et Single and weaken their conclusion that removal of regional nodes is important for the long-term survival even when such nodes are interpreted as pathologically negative.
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