Abstract
HER2 or c-ERBB2/neu is a member of the epidermal growth factor receptor (EGFR) family and encodes a tyrosine kinase receptor. Overexpression of HER2 protein is generally attributable to gene amplification. HER2 is overexpressed in 20–30% of primary invasive breast carcinomas and in a greater proportion of in situ breast cancers. Invasive breast cancers that overexpress HER2 are generally higher stage, show lymph node positivity, and have higher S-phase. Moreover, they are often associated with poor prognosis, particularly in node-positive patients. Microarray studies have subdivided breast cancers into several subtypes. HER2-overexpressing ER-negative tumors are generally classified within a single subtype denoted ERBB2-overexpressing. However, ER-positive HER2-overexpressing tumors are usually intermixed with other ER-positive tumors that do not show HER2 overexpression. Our recent population-based study evaluating HER2 overexpression and hormone receptor status has unexpectedly found that the majority of HER2-overexpressing tumors are hormone receptor-positive and are more common than HER2-overexpressing ER-negative breast cancers. This implies that the ERBB2-overexpressing molecular subtype, which is associated with ER-negative status, only includes a minority of HER2-overexpressing tumors. We therefore studied gene expression patterns of HER2-overexpressing breast cancers and found several tumor subtypes with distinctive molecular signatures. These ERBB2-overexpressing subtypes spanned the range of hormone receptor status and highlighted different biological characteristics. Since the clinical course varies among patients with HER2-positive tumors, as does their response to targeted therapy, differences in global gene expression among HER2-overexpressing tumors could be important in distinguishing patients for the design and delivery of individualized targeted therapies.
Highlights
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
We found that the frequency of the IVS10-6T>G is characterized by multiple physiologic abnormalities, including mutation was not increased in breast cancer cases as compared with neurodegeneration, immunologic abnormalities, cancer predisposition, controls
We examined the incidence of tumors the hypothesis that Single nucleotide polymorphisms (SNPs) in the regulatory regions of genes that create formed in these ERα knockout mice bearing the Wnt-1 transgene
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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