Abstract
Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. Especially, an accurate method for breast cancer detection based on peripheral blood as a clinical sample will be highly desirable because of the easy accessibility and less-invasive nature by which samples can be obtained. Results demonstrating that peripheral blood can be used to develop a gene expression based test for early detection of breast cancer will be presented. The rationale for using blood cells as monitors for a malignant disease elsewhere in the body is based on the hypothesis that a malignant growth will cause characteristic changes in the biochemical environment of blood. These changes will affect the expression pattern of certain genes in blood cells. We initially conducted a pilot study where the expression pattern of 1368 genes in peripheral blood cells of 24 females with breast cancer and 32 females with no signs of this disease were analyzed using macroarrays and the expression data analyzed by PAM. The results were validated using a standard leave-one-out cross-validation approach. We were able to identify a set of genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of the identified genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defence-related genes was increased in samples from breast cancer patients. In order to revalidate these findings and to increase the repertoire of informative genes, we have now extended the study with a larger number of breast cancer and non-breast cancer samples and used Agilent WG oligo arrays for large-scale gene expression analysis. The preliminary analysis of the data supports our previous finding that a blood-based gene expression test can potentially be developed to detect breast cancer in asymptomatic patients.
Highlights
Endocrine therapy for breast cancer is a major modality for the treatment of breast cancer, producing response rates between 30% and 40% of unselected patients with the minimum of toxicity
We have shown that overexpression of TGF-β1 in mammary epithelial cells suppresses the development of carcinomas and that expression of a dominant negative type II TGF-β receptor (DNIIR) in mammary epithelial cells under control of the MMTV promoter/enhancer increases the incidence of erbB2 in carcinomas accompanied by Tgfbr2fspKO fibroblasts
The present article reviews results from neoadjuvant studies in which endocrine therapy was given to patients whose primary breast cancer was still within the breast so that changes in tumour volume could be used to assess clinical response and so that sequential biopsies could be taken for molecular analyses designed to identify predictive markers
Summary
Endocrine therapy for breast cancer is a major modality for the treatment of breast cancer, producing response rates between 30% and 40% of unselected patients with the minimum of toxicity. Several human genetic diseases are known to be or suspected to be due to defects in DNA repair or cell cycle control Some of these patients are radiation sensitive and/or predisposed for cancer as a cause of mutations in genes involved in these cellular pathways. Microarray-based comparative genomic hybridization (arrayCGH) allows the construction of high-resolution genome-wide maps of copy number alterations, and statistical software packages are available for exploring and analysing array-CGH data (see, for example, [2,3]), facilitating the delineation of the boundaries of CNAs in individual tumors and thereby localizing and identifying potential oncogenes and tumor suppressor genes. The aim of this study was to evaluate the prognostic value of gene expression-based classification as well as established prognostic markers, including mutation status of the TP53 gene, in a group of breast cancer patients with long-term (>10 years) fol The aim of this study was to compare MR spectroscopic findings from breast cancer tissue with histological grading of tumor and patient lymph node status
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