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Targeted therapy in breast cancer: the HER-2/neu gene and protein
Jeffrey S Ross1, Jonathan A Fletcher, Kenneth J Bloom
1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY 12208, USA. rossj@mail.amc.edu
Abstract:
The HER-2/neu oncogene, a member of the epidermal growth factor receptor or erb gene family, encodes a transmembrane tyrosine kinase receptor that has been linked to prognosis and response to therapy with the anti-HER-2-humanized monoclonal antibody, trastuzumab (Herceptin, Genentech, South San Francisco, CA) in patients with advanced metastatic breast cancer. HER-2/neu status has also been tested for its ability to predict the response of breast cancer to other therapies including hormonal therapies, topoisomerase inhibitors, and anthracyclines. This review includes an analysis of 80 published studies encompassing more than 25,000 patients designed to consider the relative advantages and disadvantages of the various methods of measuring HER-2/neu in clinical breast cancer specimens. Southern blotting, PCR amplification detection, and fluorescence in situ hybridization assays designed to detect HER-2/neu gene amplification are compared with HER-2/neu protein overexpression assays performed by immunohistochemical techniques applied to frozen and paraffin-embedded tissues and enzyme immunoassays performed on tumor cytosols. The significance of HER-2/neu overexpression in ductal carcinoma in situ and the HER-2/neu status in uncommon female breast conditions and male breast cancer are also considered. The role of HER-2/neu testing for the prediction of response to trastuzumab therapy in breast cancer is reviewed along with the current studies designed to test whether HER-2/neu status can predict the response to standard and newer hormonal therapies, cytotoxic chemotherapy, and radiation. The review will also evaluate the status of serum-based testing for circulating HER-2/neu receptor protein and its ability to predict disease outcome and therapy response.
Insights
HER-2/neu testing is crucial for predicting breast cancer patient response to trastuzumab and other therapies. This review analyzes methods for measuring HER-2/neu status, aiding treatment decisions.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The HER-2/neu oncogene encodes a receptor tyrosine kinase implicated in breast cancer prognosis and therapy response.
- HER-2/neu status influences treatment decisions, particularly for anti-HER-2 therapies like trastuzumab.
Purpose of the Study:
- To review and compare various methods for measuring HER-2/neu in clinical breast cancer specimens.
- To evaluate the predictive value of HER-2/neu status for response to trastuzumab, hormonal therapies, chemotherapy, and radiation.
- To assess the utility of serum-based HER-2/neu testing for predicting outcomes.
Main Methods:
- Analysis of 80 published studies involving over 25,000 patients.
- Comparison of gene amplification detection methods (Southern blotting, PCR, FISH) with protein overexpression assays (IHC, EIAs).
- Review of studies on HER-2/neu in ductal carcinoma in situ, uncommon breast conditions, and male breast cancer.
Main Results:
- Various methods exist for HER-2/neu assessment, each with advantages and disadvantages.
- HER-2/neu status is a key predictor for trastuzumab efficacy.
- HER-2/neu testing also shows potential for predicting response to other breast cancer treatments.
Conclusions:
- Accurate HER-2/neu testing is vital for personalized breast cancer therapy.
- Understanding HER-2/neu status guides the selection of targeted therapies, improving patient outcomes.
- Further research into serum-based testing may offer non-invasive predictive capabilities.
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