Clinico-pathologic characteristics.

<p>Clinico-pathologic characteristics.</p

Breast cancer specific survival according to Ki67 expression.

<p>Survival curves (Kaplan-Meier) are shown for Ki67 expression on WS (A); TMA (B) and CNB (C). Cut-off points at the median were applied for all specimen categories. The number of events and total number of patients in each group are shown beside the description of each curve. Numbers at risk are presented below each curve.</p

Ki67 counts according to tissue categories.

<p>WS, whole sections; CNB, core needle biopsies; TMA, tissue micro arrays.</p><p>Ki67 counts according to tissue categories.</p

Box plots of tumor cell proliferation by Ki67 expression according to breast cancer molecular subgroups in different specimen categories.

<p>Horizontal lines inside the boxes represent the median value; box limits indicate the 25th and 75th percentiles; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles.</p

Frequency of cases in the Luminal/HER2- subgroup showing high proliferation when applying a Ki67 cutoff-point of 14% to different specimen categories.

<p>WS (<i>n</i> = 415), CNB (<i>n</i> = 125), TMA (<i>n</i> = 350).</p

Multivariate survival analysis (Cox′ proportional hazards method) using different specimen categories.

<p>HR, Hazard ratio; CI, confidence interval.</p><p>Final models after initial inclusion of age, tumor diameter, histologic grade, nodal status and Ki67.</p><p>5 cases (WS), 1 case (CNB) and 4 cases (TMA) were excluded due to missing information on lymph node status.</p>a<p>Likelihood ratio.</p>b<p>Cut-off point at the median.</p><p>Multivariate survival analysis (Cox′ proportional hazards method) using different specimen categories.</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 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

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