Human epidermal growth factor receptor 2 testing in breast cancer

TO THE EDITOR: We read with great interest the joint recommendations from the American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) concerning human epidermal growth factor receptor 2 (HER-2) testing in breast cancer. The new recommendations are highly appreciated, and the validation, standardization, and accreditation initiatives are very important for increasing accuracy in HER-2 testing. The joint ASCO/CAP guideline is based on a comprehensive review of published data on HER-2 testing, except for the recommendation for changing the cutoff of stained cells from 10% to 30%. Most published data are based on results obtained using a US Food and Drug Administration (FDA) –approved test that defines a positive 3 staining as being uniform, intensive membrane staining of more than 10% of invasive tumor cells. The new guideline recommends a different cutoff of 30% for 3 . It is not clear whether there are data that support this new cutoff, and we recommend the publication of data from clinical trials to do so. As a point of correction, we wish to bring to your attention that Dako (Glostrup, Denmark) has a US FDA–approved assay, the HER2 FISH (fluorescence in situ hybridization) pharmDx Kit (Dako Denmark A/S). This kit is indicated as an aid in the assessment of patients for whom Herceptin treatment is being considered. The cutoff stated in the package inserts of the approved tests will still be the legally valid cutoff, and it will be impossible to change it without presenting the US FDA with valid data that correlate to clinical outcome. We are concerned that the divergence between the recommendations in the package inserts of the approved HER-2 tests and the ASCO/CAP guideline concerning cutoff will generate confusion rather than clarification.