Biotechnology Healthcare - September/October 2008 - (Page 27)

As many as 2,000 women a year whose IHC test resulted in a false HER2negative and who might have benefitted from trastuzumab therapy will relapse with breast cancer, according to one expert. mendations are, there is reason to believe that they have missed an opportunity to raise the quality bar for HER2 assays even higher. Press is a coauthor of the ASCO/ CAP Guideline Recommendations, and he agrees with “95 percent” of the finished document. “However, I don’t agree with the ASCO/CAP Guidelines that suggest that immunohistochemistry is OK,” says Press. “I do not think that immunohistochemistry done even in the best laboratories and with the best pathologists is good enough, because the method is flawed.” This is hardly news, at least not after 20 years of research published in peer-reviewed journals. Even more curious is that consumer Web sites such as «www.breastcancer. org» repeat Press’s and Ross’s assertions almost verbatim. Here’s an excerpt from this site’s text on Immunohistochemistry under “Will Herceptin Work for You?”: “The IHC test results are most reliable for fresh or frozen tissue samples. IHC tends to be an unreliable way to test tissue that’s preserved in wax or other chemicals. FISH testing is the preferred way to assess preserved tissue samples.”2 affected by conditions of the testing procedures. These include: time to fixation, duration of fixation, processing, denaturation, heating, antigen retrieval, the staining procedure used, and the interpretation of staining. Although there are antigen retrieval techniques in use, these may result in false-positive IHC results. FISH measures HER2 DNA. Some fixatives, chemicals or heat, may interfere with the FISH assay. However, an internal control is used to distinguish between a FISH-negative and a non-informative result.3 Genentech’s «www.Herceptin. com» site includes the following under FAQs: Q. Which variables can affect the performance of IHC and FISH? A: IHC detects HER2 overexpression at the protein level, and may be The ASCO/CAP Guideline Recommendations mention a newly available bright field [as opposed to fluorescent] ISH assay and a new chromogenic assay in the FDA pipeline. Until these new assays prove themselves in practice, surgeons and radiologists will continue to send tissue samples for IHC and FISH HER2 testing, and breast oncologists will continue to weigh the results along with other prognostic factors in planning treatment for their patients. Citron, the breast oncologist from Einstein College of Medicine, is sticking by his initial reaction at the 2007 ASCO meeting that we still don’t know how to test for HER2. He’s also not convinced that FISH is any kind of gold standard, pointing out that “Table 2 of the package insert for Herceptin shows IHC pre2 dicts better than FISH for response to the drug.” Citron is concerned, however, that the ASCO/CAP Guideline Recommendations appear to have eliminated the possibility of false positive HER2 test results, regardless of which assay is used. “The problem is that clinicians may get discrepant values, for example, between a patient who tests positive on core [biopsy], and then is negative on the specimen for IHC and for FISH,” Citron explains. “According to the ASCO/ CAP Guidelines, any patient who tests positive either by IHC or by FISH is a candidate for trastu zumab. It’s possibly a false positive, but there’s no way to prove that right now, and those patients end up being treated as HER2positive patients.” REFERENCES Pollack A. Cancer drug may elude many women who need it. New York Times. June 12, 2007. «http://www.nytimes. com/2007/06/12/health/12canc.html». Accessed Sept. 5, 2008. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007a;25: 118–145. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007b;131:18. 3 «http://www.breastcancer.org/treatment/ targeted_therapies/herceptin/ will_it_work.jsp» «http://www.herceptin.com/herceptin/ professional/testing/faqs.jsp» Bob Carlson, MHA, writes exclusively about healthcare. He lives near Zionsville, Ind. SEPTEMBER/OCTOBER 2008 · BIOTECHNOLOGY HEALTHCARE 27 http://www.breastcancer.org http://www.breastcancer.org http://www.nytimes.com/2007/06/12/health/12canc.html http://www.nytimes.com/2007/06/12/health/12canc.html http://www.Herceptin.com http://www.Herceptin.com http://www.breastcancer.org/treatment/targeted_therapies/herceptin/for_you.jsp http://www.herceptin.com/herceptin/professional/testing/faqs.jsp

Table of Contents Feed for the Digital Edition of Biotechnology Healthcare - September/October 2008

Biotechnology Healthcare - September/October 2008 Openers Editorial/David B. Nash, MD, MBA Contents At a Glance: Multiple Sclerosis Drug Track Personalized Medicine Healthcare Reform’s Effects on Biologic Access Breast Cancer Status Testing: A Crapshoot With Deadly Odds Trends, Issues, and Perspectives In the Management of MS So High-Tech, Yet So Simple The Evolution of Ascertaining the Value Proposition Specialty Pharmacy Employer to Employer Health Plan Confidential Trends

Biotechnology Healthcare - September/October 2008

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