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

Univariate survival analysis of proliferation markers examined in lymph node metastases (<i>n</i> = 168).

<p>Univariate survival analysis of proliferation markers examined in lymph node metastases (<i>n</i> = 168).</p

Survival analysis for Ki-67 and mitotic count in primary tumors and LN metastases.

<p>Survival curves (Kaplan-Meier method) are shown for Ki-67 in PT and LN metastasis (a. and b.), and MC for PT and LN metastasis (c. and d.). Number of events / number of cases are given in parenthesis.</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

Ki-67 expression and histopathologic features of the primary tumors.(<i>n</i> = 168).

<p>Ki-67 expression and histopathologic features of the 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

Kaplan-Meier curves showing the relationship between number of positive nodes (A), TD-MET (B), AVI (C), EVI (D) and time to first event.

<p>The number of events/number of cases in each subgroup is given in parenthesis. Abbreviations; TD-MET, metastatic tumor diameter; AVI, afferent vascular invasion; EVI, efferent vascular invasion. One case with missing data on the number of positive nodes because of fused axillary nodes in a locally advanced breast cancer and three other cases were not included in the measurement of TD-MET as tumor was detected only in the afferent lymphatic vessels.</p

Multivariate survival analysis (Cox`s proportional hazards method) using time to first disease recurrence (DFS) as end point.

<p><b>Number of events (46/115)</b>. Final model after including primary tumor diameter, histologic grade, no. of positive nodes, EVI, and perpendicular diameter of ENE.</p

Multivariate survival analysis (Cox`s proportional hazards method)

<p>Final model after initial inclusion of tumor diameter, histologic grade, Ki-67 in PT ^b, Ki-67 in LN ^b, MC in PT ^b, MC in LN ^b (<i>n</i> = 168).</p

Kaplan-Meier curves showing the relationship between types of ENE (A), number of ENE foci (B), CD-ENE (C), PD-ENE (D) and time to first event.

<p>The number of events/number of cases in each subgroup is given in parenthesis. Abbreviations; ENE, extra-nodal extension; CD-ENE, circumferential diameter of extra-nodal extension; PD-ENE, perpendicular diameter of extra-nodal extension. One case had missing data on measurement of extra-nodal extension diameters because of extensive fat infiltration combined with inappropriate orientation of the section.</p