Background: Breast cancer patients comprise a prognostic heterogeneous group. Stroma-tissue surrounding cancer cells plays an important role in tumor behavior. The prognostic value of the tumor-stroma ratio was evaluated.Material and Methods: A cohort of 574 patients with early breast cancer, primarily treated by surgery between 1985 and 1994 was analyzed. The percentage of intra-tumoral stroma was visually estimated on haematoxylin-eosin-stained histological sections from primary tumor tissue by two observers. Patients with more than 50% intra-tumor stroma were quantified as stroma-rich and patients with less than 50% intra-tumor stroma as stroma-poor.Results: Of all tumors, 68% were classified as stroma-rich and 32% as stroma-poor. Cohen's kappa coefficient revealed an almost perfect agreement in classification (kappa=0.85; 94% concordance in classification) between the two observers. For the total group of patients, stroma-rich tumors had a shorter relapse free period (RFP) (Hazard ratio (HR) 1.62; 95%CI 1.23-2.13; p=0.001) and overall survival (OS) (HR1.29; 95%CI 1.03-1.60; p=0.025) compared to stroma-poor tumors. Tumor-stroma ratio was an independent prognostic parameter for all patients (p<0.001) and in stratified analysis for patients that received systemic treatment. Importantly, within the triple-negative-cancer (TNC) subpopulation, patients with stroma-rich tumors had a 3.19 times higher risk of relapse (p=0.003) compared to patients with stroma-poor tumors, independently of grade and lymph node status. Five year RFP-rates for patients with stroma-rich compared to stroma-poor tumors were 56% and 81% respectively.Discussion: Tumor-stroma ratio was an independent prognostic factor for RFP in breast cancer patients, especially in TNC. The tumor-stroma ratio is easy to apply, of low cost and reproducible. It is a candidate parameter that can easily be implemented in routine daily diagnostics to optimize risk-stratification for breast cancer patients and should therefore be considered to be implemented in standard pathology reports. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3049.

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Purpose: New prognostic and predictive factors are sought for improvement of tailored treatment in early breast cancer. We examined the clinical impact of cell adhesion molecules (CAM): E-cadherin, N-cadherin, Ep-CAM and CEA. Patients and Methods: Our study population (n=574) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. A tissue micro array (TMA) of formalin-fixed paraffin-embedded tumor tissue was immunohistochemically stained for expression of mentioned CAM. The percentage of membranous stained cells was microscopically analyzed. Based on the median score, all CAM were classified in two groups: low expression versus high expression. For CEA, high expression was further subdivided based on the intensity of staining: high expression and highest expression. Results: High expression was seen for E-cadherin, N-cadherin and Ep-CAM in 49%, 46%, 27% of patients respectively. Low expression, high expression and highest expression were found in respectively 48%, 45% and 8% of cases for CEA. Low expression of E-cadherin (p=0.015) and higher expression levels of N-cadherin, Ep-CAM, CEA (p=0.004; 0.046; 0.001 respectively) all resulted in a worse relapse free period (RFP) of patients. Multivariate analysis revealed only E-cadherin and CEA to be independent prognostic variables. A combination variable was created with expression of both markers: (1) E-cadherin high expression, (2) E-cadherin low or CEA low or high expression (3) CEA highest expression. This variable revealed to be an independent prognostic parameter with high discriminative power for RFP (P<0.001, E-cadherin low or CEA low or high expression versus E-cadherin high expression: Hazard Ratio (HR)= 1.9; CEA highest expression versus E-cadherin high expression: HR= 3.6). A statistically significant interaction was found between expression of both CAM (P<0.001), suggesting a biological connection in their functioning. Conclusion: We have demonstrated that E-cadherin, N-cadherin, Ep-CAM and CEA are of prognostic influence on outcome concerning RFP in breast cancer patients. A combined variable of E-cadherin and CEA expression revealed to have prognostic influence on RFP with high discriminative power and therefore is a candidate parameter for future outcome prediction of patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-07-02.