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.
"central comparisons, this refers to the number of specimens graded as positive for HER2 by the local laboratory and confirmed positive in central laboratory; in the central vs. central comparison, this refers to the number of concordant results assessed by 3 pathologists at 3 central laboratories. that there is clinical support for the ASCO/CAP recommendations for resampling and testing HER2 status in cancers that show an equivocal result on initial FISH testing . Other data, however, suggest that the guideline-prescribed change in criteria used to define HER2-positive status may have a negative impact on patient care by restricting access to HER2-tar- geted treatment in patients who could benefit from such treatment. "
[Show abstract][Hide abstract] 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 · 7.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Identifying breast cancers with HER2 overexpression or amplification is critical as these usually imply the use of HER2-targeted
therapies. DNA (amplification) and protein (overexpression) HER2 abnormalities usually occur simultaneously and both in situ hybridisation and immunohistochemistry may be accurate methods for the evaluation of these abnormalities. However, recent
studies, including those conducted by the Association for Quality Assurance of the Spanish Society of Pathology, as well as
the experience of a number of HER2 testing National Reference Centres have suggested the existence of serious reproducibility
issues with both techniques. To address this issue, a joint committee from the Spanish Society of Pathology (SEAP) and the
Spanish Society of Medical Oncology (SEOM) was established to review the HER2 testing guidelines. Consensus recommendations
are based not only on the panellists’ experience, but also on previous consensus guidelines from several countries, including
the USA, the UK and Canada. These guidelines include the minimal requirements that pathology departments should fulfil in
order to guarantee proper HER2 testing in breast cancer. Pathology laboratories not fulfilling these standards should make
an effort to meet them and, until then, are highly encouraged to submit to reference laboratories breast cancer samples for
which HER2 determination has clinical implications for the patients.
[Show abstract][Hide abstract] 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
Sally R. Coassin, Byung-Chul Kim, Hans E. Johansson
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