Clinical significance of extranodal extension in sentinel lymph node positive breast cancers

Background: The precise stage of lymph node (LN) metastasis is a strong prognostic factor in breast cancer, and sentinel lymph node (SLN) is the first station of nodal metastasis, whereas the clinical value of extranodal extension (ENE) in SLN are still in exploration. Objective: Our study aimed to evaluate the predictive and prognostic values of ENE in SLN and to investigate the feasibility of ENE to predict non-SLN metastasis, disease free survival (DFS) and overall survival (OS) in clinical practice. Methods: 183 cases of primary invasive breast cancer (cT1-2N0 breast cancer with 1-2 positive SLNs) underwent SLN biopsy and axillary lymph node dissection (ALND) between 2008 and 2015 were extracted from the pathology database of Fudan University Shanghai Cancer Center. Sections were reviewed for the microscopic features of SLN, including the number and pattern of SLN metastasis, SLNs positive ratio, nodal vascular invasion (NVI), and ENE. The associations between tumor features including ENE and non-SLN metastasis, DFS and OS were analyzed. Moreover, ENE was subclassified into circumferential (CD-ENE) and perpendicular (PD-ENE) and set a threshold as 2mm or 3mm to evaluate the prognostic value of ENE. Results: 73/183 (39.9 %) cases were positive for ENE in SLN. Logistic regression analysis indicated that ENE, the number and pattern of SLN involvement, SLN positive ratio, and NVI were significantly associated with the presence of non-SLN metastasis in univariate analysis. ENE, higher number of SLN involvement, SLN macrometastasis, and NVI were significantly associated with a higher rate of non-SLN metastasis in multivariate analysis . Cox regression analysis showed ENE in SLN was associated with DFS and OS in univariable analysis, but not in multivariable analysi s. Whereas the size of ENE (CD-ENE and PD-ENE) subdivided by 3mm (or 2mm) cutoff values were not found as strongly prognostic factors of DFS and OS as well. Conclusions: Our study indicated that ENE in SLN was a predictor for non-SLN metastasis in breast cancers, patients with ENE in SLN had a higher rate of non-SLN metastasis. ENE in SLN was associated with DFS and OS in univariable analysis, but not in multivariable analysi s. The size of ENE (CD-ENE and PD-ENE) which was classified by a 3mm (or 2mm) cutoff value had no significant prognostic values in this study. The prognostic value of ENE in SLN and the cutoff values of ENE in SLN in breast cancers need further investigation.