Current status of HER2 testing: caught between a rock and a hard place.

The analysis of breast cancer specimens for alterations in the HER2/neu (c-erb-B2) gene or its protein product has become common practice in surgical pathology laboratories. Although some clinicians use the information derived from these assays for assessing patient prognosis and evaluating the likelihood of response to various chemotherapeutic agents and to tamoxifen, the major clinical role of assessment of HER2 status is to help determine patient suitability for treatment with trastuzumab (Herceptin), a monoclonal antibody targeted to the HER2 protein.1,2 Although there are a variety of methods available to assess HER2 status in clinical breast cancer specimens, assessment of protein overexpression using immunohistochemical analysis and evaluation of gene amplification using fluorescence in situ hybridization (FISH) are the methods most commonly used in clinical practice today.3,4 There are currently 4 commercially available, US Food and Drug Administration–approved assays for determining HER2 status in breast cancer samples, although these have not all been approved for the same purpose ❚Table 1❚. Among these 4 assays, 2 are immunohistochemical assays (HercepTest, DAKO, Carpinteria, CA; and Pathway, Ventana Medical Systems, Tucson, AZ) and 2 are FISH assays (PathVysion, Vysis, Downers Grove, IL; and Inform, Ventana). All of these assays can be performed using automated instrumentation. In addition, there are numerous commercially available anti-HER2 primary antibodies and immunohistochemical detection systems for HER2 testing for which Food and Drug Administration approval has not been sought or received. While the clinical value of assessing HER2 status in human breast cancers to help determine suitability for trastuzumab therapy is indisputable, the manner in which the test should be performed and the results evaluated and reported is a matter of heated debate and controversy involving several groups with somewhat different (and sometimes conflicting) agendas including pathologists, medical oncologists, basic scientists, commercial vendors, the lay press, and patients and their families. The College of American Pathologists recently issued recommendations regarding HER2 testing for patients with breast cancer.5 However, these recommendations largely reflect the current lack of consensus with regard to how best to evaluate HER2 status.