Abstract
Presence of lymph node (LN) metastasis is a strong prognostic factor in breast cancer, whereas the importance of extra-nodal extension and other nodal tumor features have not yet been fully recognized. Here, we examined microscopic features of lymph node metastases and their prognostic value in a population-based cohort of node positive breast cancer (n = 218), as part of the prospective Norwegian Breast Cancer Screening Program NBCSP (1996–2009). Sections were reviewed for the largest metastatic tumor diameter (TD-MET), nodal afferent and efferent vascular invasion (AVI and EVI), extra-nodal extension (ENE), number of ENE foci, as well as circumferential (CD-ENE) and perpendicular (PD-ENE) diameter of extra-nodal growth. Number of positive lymph nodes, EVI, and PD-ENE were significantly increased with larger primary tumor (PT) diameter. Univariate survival analysis showed that several features of nodal metastases were associated with disease-free (DFS) or breast cancer specific survival (BCSS). Multivariate analysis demonstrated an independent prognostic value of PD-ENE (with 3 mm as cut-off value) in predicting DFS and BCSS, along with number of positive nodes and histologic grade of the primary tumor (for DFS: P = 0.01, P = 0.02, P = 0.01, respectively; for BCSS: P = 0.02, P = 0.008, P = 0.02, respectively). To conclude, the extent of ENE by its perpendicular diameter was independently prognostic and should be considered in line with nodal tumor burden in treatment decisions of node positive breast cancer.
Highlights
Axillary lymph node metastasis is a key prognostic factor in breast cancer
The prognostic impact of nodal microstaging in lymph node positive breast cancer is being discussed[1]
The perpendicular diameter of the largest focus of extranodal extension was found to be an independent factor by multivariate analysis of disease-free and breast cancer specific survival
Summary
Axillary lymph node metastasis is a key prognostic factor in breast cancer. Still, stratification of node-positive cases into different categories, based on nodal tumor features, could assist in PLOS ONE | DOI:10.1371/journal.pone.0171853 February 15, 2017. Extra-nodal extension (ENE) is a commonly observed microscopic feature in positive nodes (20–60%) and may be important to better identify patients at increased risk of loco-regional or distant relapse [4,5,6,7,8,9,10,11]. Such cases might benefit from adjuvant therapy [4, 12]. The aim of this study was to examine microscopic features of nodal breast cancer metastases, like metastatic tumor diameter, nodal afferent- and efferent vascular invasion, and extranodal extension, and to study the potential prognostic importance of these nodal characteristics
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