title: Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer.
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.
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Sura
authors.initials: S
authors.lastname: Aziz
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wik
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Gøril
authors.initials: G
authors.lastname: Knutsvik
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Vestfold Hospital Trust, Tønsberg, Norway.
authors.forename: Tor Audun
authors.initials: TA
authors.lastname: Klingen
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Akerhus University Hospital, Lørenskog, Norway.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Surgery, Haukeland University Hospital, Bergen, Norway.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Davidsen
authors.affiliation: Department of Surgery, Vestfold Hospital Trust, Tønsberg, Norway.
authors.forename: Hans
authors.initials: H
authors.lastname: Aas
authors.affiliation: Department of Surgery, Haukeland University Hospital, Bergen, Norway.
authors.forename: Turid
authors.initials: T
authors.lastname: Aas
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies