Association between the 18-gene signature score and response to treatment (mean signature score is given).

1<p>Near-complete pathologic response,</p>2<p>Pathologic complete response,</p>3<p>No response,</p>4<p>Partial respons,</p>5<p>Mann-Whitney U test,</p>6<p>Residual disease.</p

Multivariate survival analysis (Cox' proportional hazards regression model) of the vascular invasion signature score.

1<p>Adjusted Hazard ratio,</p>2<p>95% confidence interval,</p>3<p>Lratio test, Final model after inclusion of: ⁴Vascular invasion score, histologic grade and molecular subtype or ⁵Vascular invasion score and molecular subtype.</p><p>Data presented for disease specific survival, overall survival and recurrence free survival.</p

Associations between ER-status, PR-status, HER2-status and the 18-gene vascular invasion signature score (mean signature score is given).

1<p>Mann-Whitney U test, significance level 0.05.</p

High Vascular Invasion Signature score is associated with reduced recurrence free survival.

<p>High signature score is associated with reduced recurrence free survival in data sets GSE1456, GSE2506 and GSE20685. In data set GSE7849, there is a trend between high signature score and reduced recurrence free survival. Survival curves are estimated by the Kaplan-Meier method (log-rank significance test). For each category, the number of cases is given followed by the number of breast cancer deaths.</p

High Vascular Invasion Signature score is associated with reduced survival.

<p>High signature score is associated with reduced survival in datasets GSE1456 and GSE20685. Univariate survival analysis was performed by the Kaplan-Meier method (log-rank significance test). For each category, the number of cases is given followed by the number of breast cancer deaths.</p

High Vascular Invasion Signature score is associated with Basal-like and HER2 molecular subtypes.

<p>High signature score is associated with Basal-like and HER2 molecular subtypes among data sets GSE25066, GSE22358, GSE1456 and GSE20685. Correlations were assessed by Kruskal-Wallis test. Mean expression signature scores indicated by circles, and the bars represent standard error ±2.</p

The vascular invasion signature consists of 7 up-regulated and 11 down-regulated genes [5].

<p>The vascular invasion signature consists of 7 up-regulated and 11 down-regulated genes <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098787#pone.0098787-Mannelqvist2" target="_blank">[5]</a>.</p

Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer

<div><p>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 (<i>n</i> = 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: <i>P</i> = 0.01, <i>P</i> = 0.02, <i>P</i> = 0.01, respectively; for BCSS: <i>P</i> = 0.02, <i>P</i> = 0.008, <i>P</i> = 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.</p></div

Univariate survival analysis of features of primary tumors (<i>n</i> = 168).

<p>Univariate survival analysis of features of primary tumors (<i>n</i> = 168).</p

Photographs of metastatic tumor tissue in axillary lymph nodes demonstrating extra-nodal extension.

<p>A, the partial type with foci of extra-nodal extension (arrows); B, complete type with total destruction of the lymph node capsule (x 200 magnification).</p