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Overexpression of HER-2/neu in primary breast cancer would predict metastases to the sentinel lymph nodes
Our study, a retrospective review of 1063 sentinel lymph node biopsies (SLNBs) in a nonrandomized prospective study of 1055 breast cancer patients, found tumor size and HER-2/neu status to be significantly associated with positive SLNs. A higher tumor grade was only marginally associated with an increased likelihood of SLN metastasis. The other variables where evaluated for a possible association, and none was found to be significant, included age, hormone receptor expression, type of surgery and the surgeon doing the procedure. Much of the information in the literature on the clinical value of HER-2/neu in primary breast cancers has focused on its value as a prognostic variable for survival or as a predictor of response to the humanized monoclonal anti HER-2/neu antibody trastuzumab. Reported predictors of axillary lymph node (ALN) status identified include tumor size, grade, lymphovascular invasion, and age, but no significant association between HER-2/neu expression and positive SLNs had been identified. One study did show that HER-2/neu over expression is associated with multiple positive nodes. The discrepancy with our data may be a result of the initial lack of standardization of the assay methods, the lack of uniformity when HER-2/neu assays are done in different laboratories, the relatively small number of patients in other studies, and the accuracy of lymph node analyses in studies relying on ALN dissection and its lower chance of identifying positive lymph nodes compared to SLNB. The advantage of our study is that only two people read the IHC assays and one person performed the FISH assays; the protocols for the assays were rigidly followed and our overall positivity rate (14%) is relatively low compared to the reports in the literature. This suggests that a higher rate of breast cancer patients with HER-2/neu positive tumors may have included some that were falsely positive, especially if a confirming FISH assay were not performed. Such false positive results could adversely skew the data analyzed. The simplifications of breast cancer surgical management over the past few decades help us anticipate a future when not only ALND but also SLNB may be avoided. Simple pathological information from needle biopsies of primary tumors may be enough to determine which patients may not significantly benefit from SNLB. Our HER-2/neu data are not compelling enough to incorporate the information into patient management decisions at this time. Perhaps future molecular information, such as the multigene array technology recently reported, plus the addition of HER-2/neu data, shown here to be a significant predictor of SLN metastases, will even further enhance our ability to safely omit SLNB in the future.
Bibliographical reference:
David Nathanson Department of Surgery, Henry Ford Health System, Detroit, Michigan, USA
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