Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer

Abstract

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. 1 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 3ϩ 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 3ϩ. 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. 2 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 clin-ical 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.

Effects of the Change in Cutoff Values for Human Epidermal Growth Factor Receptor 2 Status by Immunohistochemistry and Fluorescence In Situ Hybridization: A Study Comparing Conventional Brightfield Microscopy, Image Analysis-Assisted Microscopy, and Interobserver Variation

“…However, it is not known how many patients the new guidelines will affect by providing either a different, or a double equivocal, diagnosis. [16][17][18] To investigate the effect of part of these new guidelines, and especially the new cutoff values (ie, 3+ at 30%), we initiated a study of 150 invasive breast cancer specimens, interpreted by the FDA-approved HER2 FISH pharmDx assay (Dako) and the HercepTest, and scored by 7 different pathologists. The results were compared with the ASCO/CAP criteria for HER2 FISH and to a 30% cutoff (30% cutoff for all scores: 1+, 2+, and 3+).…”

Twenty-five years with HER2 targeted therapy

“…To standardize and improve the accuracy of HER2 testing in breast cancer, the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) issued a clinical practice guideline in 2007 ( 67 ). One of the problems with this first version of the guideline was that the scoring criteria deviated from the FDA-approved scoring criteria, which until then had been used in all pivotal clinical trials with trastuzumab ( 68 , 69 ). However, with the revision of the ASCO/CAP guidelines in 2013 and 2018, the scoring criteria became similar to the original FDA-approved criteria ( 70 , 71 ).…”

A Companion Diagnostic With Significant Clinical Impact in Treatment of Breast and Gastric Cancer

“…As part of the guideline, in order to improve the robustness of the HercepTest ™ scoring, it was suggested to change the requirements for HER2 IHC3+ from a > 10% strong complete membrane staining of the tumor cells to > 30%. This change was highly questioned as no clinical outcome data was available to support the 30% requirement, as all pivotal clinical trials with trastuzumab had used the original FDA approved scoring criteria (37,38). The use of the suggested ASCO/CAP scoring criteria would identify a slightly different patient population compared to the populations in the different clinical trials with trastuzumab (39).…”