Clinicopathological parameters and biological markers predicting non-sentinel node metastasis in sentinel node-positive breast cancer patients

The value of complete axillary lymph node dissection (ALND) has been questioned in invasive breast cancer (IBC) patients with positive sentinel lymph nodes (SLNs) who have no non-sentinel lymph node (NSLN) metastases. Because biological markers have not been systematically studied in this setting, we sought to identify clinicopathological characteristics and biological markers for predicting NSLN metastases in SLN-positive IBC patients. Two hundred and five IBC patients who had at least one positive SLN and received SLN biopsy and ALND were included in our study. We examined the clinicopathological characteristics of their primary tumors, SLNs and NSLNs. We also evaluated the biological markers of the primary tumors by tissue microarray and immunohistochemistry. Of the 205 patients with SLN metastases, 89 patients (43.4%) had additional metastases in NSLNs. The following factors were found to be associated with NSLN metastases: peritumoral lymphovascular invasion (p=0.01), two or more metastatic SLNs (p<0.01), SLN metastasis >2.0 mm (p<0.01) and extra-nodal extension (p<0.01). Primary tumors >2.0 cm showed more NSLN metastases, but the association was statistically insignificant (p=0.08). In contrast, NSLN metastases were not associated with histologic grade, histologic type, presence of extensive intraductal component, presence of high grade ductal carcinoma in situ and number of harvested SLNs. Biological markers such as E-cadherin, CD44, cyclin D1, p21, ER, PR, c-erbB2, p53, Ki-67, luminal (CK7, CK18, CK19) and basal (CK5, p63) markers were not useful predictors of NSLN metastasis in IBC patients with SLN metastases. Multivariate analysis revealed that SLN metastasis >2.0 mm (p=0.01), two or more metastatic SLNs (p=0.03) and extranodal extension (p<0.01) were independent predictors of NSLN metastasis. For the prediction of NSLN metastasis in IBC patients with SLN metastases, light microscopic evaluation of the number, size and extranodal extension of metastatic SLNs by hematoxylin and eosin staining appeared to be critical. However, the biological markers of primary tumor characterized by immunohistochemical staining, such as luminal and basal markers, hormone receptors, E-cadherin, CD44, cyclin D1, p21, c-erb-B2, p53 and Ki-67, did not appear to be helpful predictors.