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HER-2 Testing in Breast CancerHER-2

JAMA. 2004;292(15):1817-1818. doi:10.1001/jama.292.15.1817-b
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AUTHOR INFORMATION

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

HER-2 TESTING IN BREAST CANCER

To the Editor: Dr Yaziji and colleagues1 present a cogent argument for a cost-effective algorithmic approach to HER-2 testing of breast carcinoma based on a carefully conducted and executed study of 2963 samples. We would like to point out several issues not directly addressed in the article or the accompanying editorial.2

Three clinical assays have been approved by the Food and Drug Administration (FDA) for determination of HER-2 status of breast cancer: HercepTest (DakoCytomation, Glostrup, Denmark), Pathway (Ventana Medical Systems Inc, Tucson, Ariz), and PathVysion (Abbott Vysis, Abbott Park, Ill). The first 2 are immunohistochemistry (IHC) assays and PathVysion is a fluorescence in situ hybridization (FISH) assay. Standardized scoring criteria have also been specified for each assay. The methods described by Yaziji et al did not use the first 2 FDA-approved IHC assays; rather, the DakoCytomation polyclonal antibody A0485 was used for IHC staining, not the approved HercepTest. Furthermore, the “subtraction score” approach to evaluating IHC preparations does not appear in the scoring specifications for either FDA-approved IHC tests.3 Also, if an FDA IHC kit is modified from the specified protocol, including a customized interpretation that subtracts normal tissue staining in the evaluation of the slide, the test becomes an in-house validated assay since it is not used as approved by the FDA.

The economic conclusions represented by the authors are also of concern. They were based on reagents that are much less expensive than HercepTest. Furthermore, the direct costs of any HER-2 laboratory test become almost trivial when weighed against the enormous total costs incurred in managing a patient treated with trastuzumab.

Financial Disclosure: Drs Tubbs and Hicks currently receive research support from Ventana Medical Systems Inc and Abbott Vysis. Dr Tubbs has also received research support from DakoCytomation.

References
Yaziji H, Goldstein LC, Barry TS.  et al.  HER-2 testing in breast cancer using parallel tissue-based methods.  JAMA. 2004;2911972-1977
PubMed
Wiley EL, Diaz LK. High-Quality HER-2 testing: setting a standard for oncologic biomarker assessment.  JAMA. 2004;2912019-2020
PubMed
Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ. Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration–approved scoring system.  J Clin Oncol. 1999;171983-1987
PubMed

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Yaziji H, Goldstein LC, Barry TS.  et al.  HER-2 testing in breast cancer using parallel tissue-based methods.  JAMA. 2004;2911972-1977
PubMed
Wiley EL, Diaz LK. High-Quality HER-2 testing: setting a standard for oncologic biomarker assessment.  JAMA. 2004;2912019-2020
PubMed
Jacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ. Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration–approved scoring system.  J Clin Oncol. 1999;171983-1987
PubMed
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