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In this review, the results of the FOCUS (Female breast cancer in the elderly: Optimizing Clinical guidelines USing clinico-pathological and molecular data) program are summarized. This study was originally designed with the aim to define guidelines for the treatment of older women with breast cancer. With data from several studies within FOCUS, a prediction model can be constructed. Such a model helps to define individualized treatment for older patients with breast cancer, taking into account tumour characteristics and patient-related factors. At a clinical level, this model can provide the physician and the patient with accurate prediction to assist on the decision making of treatment strategies: this results into individualized treatment, not based on one individual marker, but on different pillars related to the patient, the tumour and the most suitable, appropriate treatment.

Background Cell adhesion molecules (CAMs) play an important role in the process of metastasis. The prognostic value of tumour expression of N-cadherin, E-cadherin, carcinoembryonic antigen (CEA) and epithelial CAM (Ep-CAM) was evaluated in patients with breast cancer. Methods A tissue microarray of the patient cohort was stained immunohistochemically for all markers and analysed by microscopy. Expression was classified into two categories, with the median score as cut-off level. For CEA, the above-median category was further subdivided in two subgroups based on staining intensity (low or high intensity). Results The cohort consisted of 574 patients with breast cancer with a median follow-up of 19 years. Below-median expression of E-cadherin (P = 0·015), and above-median expression of N-cadherin (P = 0·004), Ep-CAM (P = 0·046) and CEA (P = 0·001) all resulted in a shorter relapse-free period. Multivariable analysis revealed E-cadherin and CEA to be independent prognostic variables. Combined analysis of CEA and E-cadherin expression showed a 3·6 times higher risk of relapse for patients with high-intensity expression of CEA, regardless of E-cadherin expression, compared with patients with below-median CEA and above-median E-cadherin tumour expression (hazard ratio 3·60, 95 per cent confidence interval 2·12 to 6·11; P < 0·001). An interaction was found between expression of these two CAMs (P < 0·001), suggesting a biological association. Conclusion Combining E-cadherin and CEA tumour expression provides a prognostic parameter with high discriminative power that is a candidate tool for prediction of prognosis in breast cancer.

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 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.

Background: Classical patient and tumour characteristics are the benchmark of personalised breast cancer (BC) management. Recent evidence has demonstrated that immune and molecular profiling of BC may also play an important role. Despite evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they are infrequently accounted for when making treatment decisions for individual patients. The purpose of this study was to investigate the relevance of the tumour immune response in the major histological subtypes of BC. We also assessed the relationship between immune responses and molecular subtypes and their prognostic potential. Methods: Immunostains were done for HLA-I, HLA-E, HLA-G, Tregs, NK cells and CTLs for the composition of the immune profiles and Ki67, EGFR, CK5/6, ER, PR and HER2 for molecular profiles in 714 breast cancer patients who underwent primary surgery. Results: No significant association was found between IDC (90.6%) and ILC (9.4%) and tumour immune subtypes (P=0.4) and molecular subtypes (P=0.4). However, for the relapse-free period (RFP) tumour immune subtyping was prognostic (P=0.002) in IDC, but not ILC. Contrary to ILC, IDC patients frequently expressed higher cleaved caspase-3 and Ki67, which was prognostic. Intermediate immune-susceptible IDC expressing high cleaved caspase-3 or Ki67 showed worse RFP than those with low expression (caspase-3: P=0.004; Ki67: P=0.002); this was not seen for ILC or in high or low immune-susceptible tumour types for either IDC or ILC. Conclusions: Tumour immune characteristics and host immune responses are prognostic in IDC, but not ILC. In addition, tumour immune profiles are only prognostic in Luminal A tumours.

Comment on: The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer

Tuberculous aortitis with a tuberculous mycotic aneurysm and an aortoduodenal fistula was diagnosed in a 38-year-old man with tuberculous cervical lymphadentitis and a 3-month history of recurrent gastrointestinal bleeding, in whom extensive investigation of the digestive tract had not revealed a bleeding lesion. Either by septic embolism or by direct extension from a neighboring focus, tuberculous infection can cause a mycotic aortic aneurysm with subsequent fistulation to the duodenum.

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 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3049.

A simple method for the determination of human corneal epithelial permeability to fluorescein is presented. The method consists of applying a 1% sodium fluorescein solution to the cornea for 8 minutes by means of an eye bath, rinsing the eye, and measuring corneal fluorescence by fluorophotometry. The permeability value is calculated from the corneal fluorescein concentration immediately after the bathing period. Mean permeability value determined in 86 eyes of 46 volunteers aged 15 to 67 years (mean 30.9 years) was 0.038 nm/s +/- 0.017 SD. No significant correlation with age was found (corr. coeff. = 0.17, P = 0.28). The reproducibility was within 10%.