The equivocally amplified HER2 FISH result on breast core biopsy - Indications for further sampling do affect patient management
ABSTRACT To our knowledge, there are no universally accepted, evidence-based guidelines for how to resolve the HER2 status of tumors demonstrating equivocal amplification. The present study was based on 17 breast core biopsy specimens demonstrating invasive carcinoma with equivocal HER2 amplification, defined as an HER2/chromosome 17 centromere ratio of 1.8 to 2.2. Each case had a corresponding resection specimen, on which HER2 immunohistochemical and repeated fluorescence in situ hybridization analyses were performed. A definitive change in HER2 status based on the resection specimen occurred in 10 (59%) of 17 cases, with 4 patients (24%) becoming eligible for trastuzumab therapy and 6 (35%) triaged as ineligible. These results suggest that genetic and protein expression heterogeneity exists in tumors that show low-level HER2 gene copy numbers. For the purposes of uniform clinical management, HER2 status should be evaluated on a larger tumor sample if the core biopsy specimen demonstrates an equivocal result. These results support the recent American Society of Clinical Oncology/College of American Pathologists recommendations for further testing in cases with equivocal HER2 results.
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ABSTRACT: Accurate determination of human epidermal growth factor receptor 2 (HER2) status is critical for optimizing breast cancer outcomes. In 2007, the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) developed guidelines for HER2 testing to reduce inaccuracy. However, current ASCO/CAP criteria may restrict access to HER2-targeted therapy for some patient groups who would derive a clear clinical benefit. ASCO/CAP are currently reviewing their guidelines to further optimize HER2 testing and include emerging techniques. Guidelines are critical for optimizing care, as is ongoing research into techniques that accurately and reproducibly assess HER2 status.Cancer Treatment Reviews 09/2013; 40(2). DOI:10.1016/j.ctrv.2013.09.001 · 6.47 Impact Factor
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ABSTRACT: Information on hormone receptor and human epidermal growth factor receptor 2 (HER2) is important for making optimal therapeutic decisions for breast cancer patients. Discordance in these biomarkers between primary breast carcinomas and corresponding metastases is well documented and may lead to changes in management option. The underlying mechanisms of biomarker discordance are complicated and multifactorial. Whereas biologic evolution, intratumoral heterogeneity, and subclonal selection may account for discordance, variations in sampling, processing, staining procedure and interpretation are the important contributory yet controllable factors. This article reviews the effects of different factors on the biomarker discordance, the clinical significance and the importance of standardizing methodology and interpretation criteria.Cancer biomarkers: section A of Disease markers 01/2012; 12(6):207-18. DOI:10.3233/CBM-130316 · 1.19 Impact Factor
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ABSTRACT: HER2 breast cancer is an aggressive disease that occurs in 20 - 30% of the breast cancer population. Treatment for HER2 breast cancer includes use of an anti-HER2 monoclonal antibody, trastuzumab. Testing for HER2 is of critical importance due to the adverse side effects and substantial costs associated with this anti-HER2 treatment. Currently, two kinds of tests, Fluorescence In Situ Hybridization (FISH) and Immunohistochemistry (IHC), are FDA approved for determination of HER2 status in breast cancers. Clinical and non clinical factors that affect the choice HER2 test and the use of anti-HER2 therapy in breast cancer were analyzed using a data set containing information from six outpatient oncology clinics in the United States. The analysis showed that geographic location, cancer stage, and diagnosis date (pre- or post-publication of testing guidelines) have significant effects on choice of test. With regard to trastuzumab prescription, geographic location and HER2 status have significant effects on the prescription of trastuzumab. In addition, there was a non-significant trend for certain Medicare patients not to receive trastuzumab therapy. These findings indicate that disparities are present in breast cancer care based on geography and cancer stage, and highlight the importance of testing guidelines. The cost effectiveness of FISH vs. IHC was determined, by considering the financial and health-related costs associated with testing and subsequent treatment as well as the accuracy of each test. The results show that FISH is the optimal choice for HER2 testing and is more cost-effective than IHC. Ph.D. Committee Chair: Griffin, Paul; Committee Member: Butera, Robert; Committee Member: Halpern, Michael; Committee Member: Nichols, Richard; Committee Member: Vidakovic, Brani