Biotechnology Healthcare - September/October 2008 - (Page 24)

gene in breast cancer. Both studies were presented at the June 2007 meeting of the American Society of Clinical Oncology, in Chicago. The prevailing mood among the assembled docs and researchers was summed up by Marc L. Citron, MD, a breast oncologist in Lake Success, N.Y., and professor at Albert Einstein College of Medicine, in the Bronx. Referring to HER2 overexpression in breast cancer, the article quoted Citron as saying, “Here we are 10 years into it, and we don’t know how to test for it.” AN UNPRECEDENTED SURPRISE Both IHC and FISH assays test breast tumor tissue for overexpression or amplification of human epidermal growth factor receptor 2, commonly referred to as HER2. Most women whose tumors test positive for HER2 gene amplification — approximately 30 percent of breast cancer diagnoses — respond well to chemotherapy plus trastuzumab (Herceptin), a monoclonal antibody that binds to the HER2 protein receptors on cancer cells and cancels the instructions that tell the cells to keep growing and dividing. Developed by Genentech, trastuzumab was approved by the U.S. Food and Drug Administration in 1998, and is considered the first of the new generation of “personalized medicines” that are paired with a pharmacogenetic test (in this case, a HER2 assay). One of the studies at the ASCO meeting was presented by Soonmyung Paik, MD, a pathologist and researcher at the National Surgical Adjuvant Breast and Bowel Project (NSABP) in Pittsburgh and principal investigator of NSABP Trial B31. Edith A. Perez, MD, director of the Mayo Clinic Breast Clinic in whether HER2 is a valid marker to Jacksonville, Fla., and principal in- decide whether you’re going to use vestigator of Breast Intergroup Trial Herceptin or not.” Paik further stresses that the reliN9831, presented the other study. The two studies have much in ability of both FISH and IHC results common. Both found that a signifi- are called into question if unqualicant percentage of women whose fied labs perform the tests. breast tumors tested HER2-positive by laboratories in the cities where CULMINATION OF the women were first diagnosed CONCERNS Improving the accuracy of HER2 turned out later to be HER2-negative when tested by the “central testing is exactly what ASCO and labs” that retested tissue samples of the College of American Patholoall enrollees after the trials ended. gists had in mind when they reIn Paik’s trial, 18 percent of the leased their “Guideline Recomlocally tested HER2-positive spec- mendations for Human Epidermal imens were found to be HER2- Growth Factor Receptor 2 Testing negative by central-lab testing in an in Breast Cancer.” Authored by a initial pretrial screening. Entry cri- joint ASCO/CAP expert panel that teria were tightened, and when each included Paik and Perez, the 28enrollee’s tumor tissue page document was pubspecimen was central-lab lished simultaneously in tested, using both IHC the January 2007 issues of and FISH assays at the the Journal of Clinical end of the trial, 9.7 perOncology and Archives of cent of the enrollees tested Pathology & Laboratory HER2-negative. Medicine (Wolff 2007a, Discrepancies between Wolfe 2007b). test results from local labs In the estimaThe guideline recomand central labs are com- tion of Jeffrey S. mendations are an attempt mon. What made news Ross, MD, 3 to 4 to address concerns about this time was that, in both percent of all the accuracy of HER2 trials, even HER2-nega- immunohistotesting, concerns that pretive women in the adju- chemistry assays date Paik’s and Perez’s vant setting (those whose in the U.S. gener- studies by several years. ate a false negatumors were surgically Those concerns are subtive and are not excised before enrolling followed by a stantiated by the guideline in the trial) seem to have FISH test. recommendations, which benefited from being concede that “Approxitreated with trastuzumab. This was mately 20 percent of current HER2 unprecedented. Trastuzumab is con- testing may be inaccurate.” sidered effective only in HER2One reason why the accuracy of positive women with metastatic HER2 testing deteriorated in the breast cancer, not in the adjuvant first place may be economics. A lab setting. can buy commercially available, “There are two issues here,” says FDA-approved HER2 test kits, or it Paik, summing up the significance can develop its own in-house HER2 of the two studies. “One is how test, also known as a home brew. reproducible currently available This is a perfectly legitimate stratHER2 tests are. Number two is egy, provided the lab makes sure 24 BIOTECHNOLOGY HEALTHCARE · SEPTEMBER/OCTOBER 2008

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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