HER2 testing in the UK: consensus from a national consultation

Abstract

Objective: To gain an understanding of current attitudes among oncologists and pathologists to prospective HER2 testing in breast cancer and to gauge whether a national consensus exists regarding extent and quality of testing. Design: Qualitative study, with semi-quantitative components, using emailed questionnaires and open-ended discussion documents. Participants: 186 relevant specialists, including 76 breast oncologists and 99 pathologists, representing all but three of the UK cancer networks. Results: A strong consensus was seen in favour of universal, non-selective testing for HER2 at the point of breast cancer diagnosis. Similarly, an overwhelming majority of participants agreed that, to optimise the quality of test results, all laboratories undertaking HER2 testing should be CPA-accredited, participate in the recognised national external quality assessment scheme (UK NEQAS), and carry out a formal annual audit of its testing service. A further recommendation that testing be restricted to laboratories undertaking a minimum 250 tests per annum for immunohistochemistry and 100 tests per annum for in situ hybridisation techniques met with majority support. However, this was not a clear consensus; a significant minority of participants favoured continued use of local services falling short of these criteria. Conclusion: This study was successful in gauging national specialist opinion regarding the extent and quality assurance of HER2 testing in the UK.T he significance of HER2 overexpression in breast cancer, and its relevance to management decisions involving trastuzumab (Herceptin), has been well publicised following publication of data from landmark trials showing substantial benefit from adjuvant trastuzumab in women with HER2-positive disease.

Comprehensive immunohistochemical analysis of Her-2/neu oncoprotein overexpression in breast cancer: HercepTest™ (Dako) for manual testing and Her-2/neuTest 4B5 (Ventana) for Ventana BenchMark automatic staining system with correlation to results of fluorescence in situ hybridization (FISH)

“…Several different laboratory methods exist to identify women with a Her-2/neu amplification or overexpression. Some authors prefer the more reproducible in situ hybridizations with fluorescence, chromogen, or silver to prove the oncogene amplification [15][16][17]; others depend on immunohistochemistry to prove the protein overexpression [9,18] and, if required, applying FISH in addition. As is known, there is a big spectrum of Fig.…”

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

“…Because most of the submitting laboratories were reference laboratories that cannot control tissue fixation or storage, it has been suggested that preanalytical issues may not be the major cause of interlaboratory variability. In the United Kingdom, it has been recommended that HER-2 testing be restricted to laboratories undertaking an annual minimum of 250 IHC tests (and/or 100 FISH tests) [169]. Results from the United Kingdom National External Quality Assessment Scheme for Immunohistochemistry also suggested that the lack of reproducibility of HER-2 scoring between laboratories was not the result of tumor heterogeneity or differences in fixation or processing but rather the result of how the scoring system was applied [170].…”

HER2 discordance between primary breast cancer and its paired metastasis: tumor biology or test artefact? Insights through meta-analysis

“…HER2 status refers to the extent of HER2 protein over-expression on immunohistochemistry (IHC), or HER2 gene amplification determined by in situ hybridization (ISH) techniques. Guidelines recommend evaluation of HER2 status in every IBC [1,[12][13][14] primarily to guide treatment with molecularly targeted agents directed against the HER2 receptor. In practice, HER2 status of a primary breast cancer guides not only initial therapy but is often the basis for selection of patients with metastatic disease who may benefit from anti-HER2-directed therapies.…”