The antitumor immune response in HER-2 positive, metastatic breast cancer patients

The aim of this study was to determine the basis for anti-tumor immune reactivity observed in patients with human epidermal growth factor receptor-2 (HER-2) (3+) breast carcinoma using an in vitro model in which the role of the HER-2-specific monoclonal antibody Herceptin was also investigated. Patients with metastatic breast cancer who had their primary tumor resected were included in this study. Peripheral blood mononuclear cell (PBMC)-dependent cytotoxicity in the presence or absence of Herceptin were assessed using the survival of target breast adenocarcinoma MDA-MB-361 cells as a parameter in a (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test. We observed a significant increase in PBMC-dependent cytotoxicity when autologous serum was introduced in the assay. Furthermore, the addition of Herceptin significantly increases their cytotoxicity. These data suggest that autologous serum constitutively contains factors that might affect PBMC-dependent cytotoxic activity against HER-2 positive cancer cells

Trefoil Factor 1 in Early Breast Carcinoma: A Potential Indicator of Clinical Outcome during the First 3 Years of Follow-Up

Background. A role of an estrogen-regulated, autocrine motogenic factor was assumed to be a major biological role of trefoil factor 1 (TFF1) in breast cancer. TFF1 is regarded as a predictive factor for positive response to endocrine therapy in breast cancer patients. The aim of our study was to examine TFF1 level distribution in breast carcinomas in order to distinguish estrogen-independent from estrogen-dependent TFF1 expression and to evaluate clinical usefulness of TFF1 status in early breast cancer during the first 3 years of follow-up. Methods. The study included 226 patients with primary operable invasive early breast carcinomas for whom an equal, a 3-year follow-up was conducted. TFF1 levels as well as estrogen receptor (ER) and progesterone receptor (PR) levels were measured in cytosolic extracts of tumor samples by immunoradiometric assay or by use of classical biochemical method, respectively. Non-parametric statistical tests were applied for data analyses. Results. Statistical analysis revealed that TFF1 levels were significantly higher in premenopausal patients (p=0.02), or in tumors with: lower histological grade (p LT 0.001), positive ER or PR status (p LT 0.001, in both cases). On the basis of TFF1 level distribution between ER-negative and ER-positive postmenopausal patients with tumors of different histological grade, 14 ng/mg was set as the cut-off value to distinguish estrogen-independent from estrogen-dependent TFF1 expression in breast cancer. Depending on menopausal and PR status, positive TFF1 status identified patients at opposite risk for relapse among ER-positive patients with grade II tumors. Among ER-and and PR-positive premenopausal patients with grade II tumors, TFF1 status alone identified patients at opposite risk for relapse. Conclusions. Determination of TFF1 status might identify patients at different risk for relapse and help in making decision on administering adjuvant therapy for early breast cancer patients during the first 3 years of follow-up

Cathepsin D as an indicator of clinical outcome in early breast carcinoma during the first 3 years of follow-up

Aim: The aim of this study was to evaluate clinical usefulness of cathepsin D status in early breast cancer during the first 3 years of follow-up. Patients and methods: The study included 226 patients with histologically verified, primary operable invasive early breast carcinomas. Concentrations of estrogen receptor (ER) and progesterone receptor (PR) in breast tumor cytosols were measured by use of the classical biochemical method. The concentration of three cathepsin D forms (52-, 48- and 34-kDa proteins) was determined by a radioimmunoassay Results: On the basis of differences in cathepsin D levels either within an ER-/PR- phenotype or between this and either ER+/PR+ or ER+/PR- phenotypes, a concentration of 39 pmol/mg was determined as the cutoff value for distinguishing estrogen-regulated cathepsin D expression. Estrogen-regulated cathepsin D expression was recognized as a high-risk biomarker for low-risk (histological grade I) breast cancer patients and as a low-risk biomarker for high-risk patients (pN(+) pT2,3). Conclusion: Determination of cathepsin D status in breast cancer might identify patients at different risk for relapse and might facilitate the selection of more or less aggressive adjuvant therapy for early breast cancer patients during the first 3 years of follow-up

Different associations of estrogen receptor beta isoforms, ER beta 1 and ER beta 2, expression levels with tumor size and survival in early- and late-onset breast cancer

Background: In breast cancer, little is known about the consequences of co-expression of ER alpha with the second estrogen receptor, ER beta, and its isoforms in light of their joint prognostic value. Previously reported correlations have been based mostly on independent ER alpha and ER beta expression levels in breast tumors. Purpose: To address whether the expression ratio of ER alpha and ER beta and its isoforms may be a more important parameter than their absolute levels, we analyzed relative mRNA expression ratios of ER beta 1 to ER beta 2 and ER alpha in 74 clinical samples of invasive breast cancer including 39 early-onset and 35 late-onset breast cancers. Expression levels were correlated with clinical and histopathological parameters and disease-free interval. Results: A specific correlation of ER beta 1 expression levels with tumor size was detected in early-onset breast cancer patients and of ER beta 2 levels with tumor size in late-onset patients. Expression of both ER beta isoforms inversely correlated with expression of the two estrogen regulated genes, progesterone receptor and pS2 in both groups. Higher levels of ER beta 2 than ER beta 1 isoform were associated with a better outcome in late-onset patients. Conclusions: Our results suggest that different isoforms of ER beta may be involved in suppression of tumor growth in young and elder patients and may have different prognostic values. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Elevated plasma TGF-beta(1) levels correlate with decreased survival of metastatic breast cancer patients

Background: The role of circulating TGF-beta(1) in prognosis of breast cancer (BC) was investigated with an intention to define TGF-beta(1)-dependent high risk and low risk subsets of patients. Methods: Fifty three BC patients of all clinical stages and 37 healthy donors (HD) were analyzed for plasma TGF-beta(1) by the T beta RII receptor-based Quantikine TGF-beta(1) ELISA kit. Results: The plasma TGF-beta(1) level of Stage I/II disease (median: 0.94 ng/ml; n=10)) remained close to HD (median: 1.30 ng/ml; n = 37; p GT 0.1). In contrast, Stage III/IV disease (median: 2.34 ng/ml; n=43) exhibited highly significant TGF-beta(1) elevation (p LT 0.001) relative to HD. Further analysis revealed that TGF-beta(1) increase was predominantly attributed to Stage IV, metastatic disease patients (Q3=4.23 ng/ml) rather than to the group Stage III/IV (Q3=3.58 ng/ml). Using the plasma TGF-beta(1) concentration of 3.00 ng/ml as the cut-off value, two subgroups of patients were formed. Overall 2-year survival of the first subgroup, having elevated plasma TGF-beta(1) ( GT 3.00 ng/ml; n=10), was 10%. This was significantly decreased (p LT 0.05) compared to 52% survival observed for the second subgroup of patients with plasma TGF beta(1) values close to HD ( LT 3.00 ng/ml, n=19). Conclusion: We have performed a pilot study to determine the relationship between overall survival and TGF-beta(1) concentration in the blood of metastatic breast cancer patients. The survival was significantly reduced in the patients with elevated plasma TGF-beta(1) levels compared to that of the patients with plasma TGF-beta(1) levels close to normal. We propose that plasma TGF-beta(1) concentration may be a new tumour marker attributed to the presence of metastatic BC cells that may be used in selection of metastatic BC patients with poor prognosis. (c) 2006 Elsevier B.V. All rights reserved