| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Breast Cancer Research | ||||
| Publisher: | BIOMED CENTRAL LTD | ||||
| Place of Publication: | LONDON | ||||
| Volume: | 11 | ||||
| Number of Issue or Book Chapter: | 4 | ||||
| Date: | 2009 | ||||
| Institutions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Pathologie | ||||
| Identification Number: |
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| Keywords: | GROWTH-FACTOR RECEPTOR; INTRACELLULAR DOMAIN 4ICD; CARCINOMA IN-SITU; TRASTUZUMAB RESISTANCE; ERBB4 ISOFORM; HER2-TARGETED THERAPY; MONOCLONAL-ANTIBODY; CELL-PROLIFERATION; ESTROGEN-RECEPTOR; TYROSINE KINASES; | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 67511 |
Web of ScienceAbstract
Introduction HER2 overexpression, or rather HER2 gene amplification, is indicative for Herceptin therapy in both metastatic and pre-metastatic breast cancer patients. Patient's individual sensitivity to Herceptin treatment, however, varies enormously and spans from effectual responsiveness over acquired insensitivity to complete resistance from the outset. Thus no predictive information can be ...
Abstract
Introduction HER2 overexpression, or rather HER2 gene amplification, is indicative for Herceptin therapy in both metastatic and pre-metastatic breast cancer patients. Patient's individual sensitivity to Herceptin treatment, however, varies enormously and spans from effectual responsiveness over acquired insensitivity to complete resistance from the outset. Thus no predictive information can be deduced from HER2 determination so that molecular biomarkers indicative for Herceptin sensitivity or resistance need to be identified. Both ErbB receptor-dependent signalling molecules as well as HER2-related ErbB receptor tyrosine kinases, known to mutually interact and to cross-regulate each other are prime candidates to be involved in cellular susceptibility to Herceptin. Methods Using immunohistochemistry and fluorescence in situ hybridisation, we retrospectively investigated primary breast cancer tissues from 48 patients who were under Herceptin treatment. We quantified the gene copy numbers of all HER receptors and evaluated their coexpression profile. Moreover the HER2 phosphorylation state, the ratio of native to truncated HER2, p27(kip1) and PTEN expression were objects of this study. Results Above all markers investigated in this study Kaplan-Meier and Cox regression analysis revealed a significant positive impact of HER4 (co-)expression on overall survival from beginning of antibody therapy. Both HER4 expression and HER4 gene amplification emerged as independent prognostic markers in Herceptin-treated breast cancer patients and responsiveness to Herceptin turned out to be more efficient if tumour cells show HER4 expression. Conclusions Although HER4 is known to potentially exert a tumour cell killing activity and in turn to have a favourable impact in breast cancer patients we demonstrate here the first time that HER4 expression prolongs overall survival in Herceptin-treated patients. Elucidating HER4 receptor function in the context of Herceptin treatment will advance the design of highly efficient receptor targeting. By then we need to extend the analysis of breast cancer by allowing for HER2/HER4 coexpression by which valuable additional prognostic and predictive information might possibly be revealed.
Metadata last modified: 19 Dec 2024 12:11
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