Sentinel Node Micrometastases and Non-Sentinel Nodes in Breast Cancer: How Much Do We Need to Know?

Abstract

Arguably, the transition from routine axillary lymph node dissection (ALND) to sentinel lymph node (SLN) biopsy has been one of the most important improvements in quality of life for women with breast cancer in the past four decades, rivaling the substitution of breast-conserving treatment for mastectomy. As with any new surgical procedure, the details of how to perform it and how to utilize the information gained have raised many new questions. Key among these is whether patients with positive SLNs need to undergo a completion ALND or whether some subset (or perhaps even all such patients) could avoid the potential morbidity of the more radical procedure. With the opportunity for pathologists to examine just a few lymph nodes in detail, the clinical significance of finding previously unrecognized micrometastases in SLN with techniques such as immunohistochemistry (IHC) and even polymerase chain reaction assays also has not been determined. Because of the uncertainty whether such findings have any meaning for the prognosis or treatment of women with breast cancer, some guidelines recommend against even performing these specialized tests on the SLNs of breast cancer patients, or at least have registered uncertainty about their usefulness. Many institutions, including our own, have abandoned IHC on SLN, at least until the time that it becomes clearer what to do with the information. This is not to say that SLN should not be carefully and exhaustively examined by serial sectioning and hematoxylin and eosin (HE the “actual” incidence of NSLN positivity if they had been examined by IHC would certainly have been higher. Despite the fact that method of detection was a significant predictor of NSLN positivity in both univariate and multivariate analysis, the authors concluded that patients with SLN positive only on IHC, regardless of size, have a high enough risk of other nodes being positive to justify routine ALND, unless the tumors were small ( 1 cm) or 2 cm with favorable histology. The threshold for the odds of finding other nodes positive which justifies routine ALND, is somewhat arbitrary, but the implication of this result for those who do not perform IHC on SLN is that diseased NSLN are unknowingly being left in place. In contrast, reports of small series suggest that the finding of isolated tumor cells or micrometastases that are detected only by IHC has little clinical significance. Using a similar retrospective multivariate analysis, investigators at Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY), have described a nomogram that can be used to calculate the odds of finding positive NSLN after a positive SLN biopsy. This tool, which is available online (http://www.mskcc.org/ nomograms), uses tumor size, type and grade, LVI, multifocality, estrogen receptor (ER) status, method of detection of the SLN metastases (frozen section, H&E, IHC), and the numbers of positive and negative SLN as significant variables in the model. Size of micrometastases was not included in the analysis, even though their own and other studies have found this to be a significant predictor of NSLN positivity. One potential weakness of the MSKCC model may have been that some patients with positive SLN who did not undergo ALND were understandably excluded from the data set, a potential source of bias that may exist in other publications related to this issue. Nevertheless, this model performed very well in predicting NSLN involvement prospectively in a subsequent cohort of patients and outperformed clinical judgement. Data from the National Surgical Adjuvant Breast and Bowel Project’s (NSABP) Protocol B-32 presented at the most recent San Antonio Breast Cancer Symposium (SABCS) in December 2005 also suggest that it is difficult to define a subset of patients with such a low risk of NSLN involvement that ALND would not be justified. This trial randomized patients to either SLN JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 24 NUMBER 12 APRIL 2