The HercepTest Assay: Another Perspective
Authors: Froilan Espinoza, Arturo Anguiano, Patrick C. Roche, James N. Ingle
Journal: Journal of Clinical Oncology (1999)

Article Tools Correspondence Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.7.2293b Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10561288 The HercepTest Assay: Another Perspective Froilan EspinozaxFroilan EspinozaSearch for articles by this author , Arturo AnguianoxArturo AnguianoSearch for articles by this author Patrick C. RochexPatrick C. RocheSearch for articles by this author , James N. InglexJames N. IngleSearch for articles by this author Show More Quest Diagnostics/Nichols Institute, San Juan Capistrano, CAMayo Clinic, Rochester, MN https://doi.org/10.1200/JCO.1999.17.7.2293b First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical Oncology 071999In Reply: We appreciate the comments of Drs Espinoza and Anguiano regarding our recent letter and the sharing of their experience with the Dako HercepTest. The high rate (57%) of HER2 overexpression that we observed in 1,142 patients tested between June and November 1998 was achieved with Dako's polyclonal antibody (same as in the HercepTest) and a separate avidin-biotin complex detection system, not with the HercepTest kit. However, as we stated in our letter, we did have a 90% concordance between our staining system and the HercepTest in a comparison study of 80 patients. The high level of overexpression that we experienced between June and November 1998 may have been due to testing of a larger proportion of patients with recurrent disease following the May 1998 publication of the efficacy of trastuzumab (Herceptin). Between January and April 1999, we have used the HercepTest to assay 1,016 breast cancers. Three hundred sixty-four tumors (36%) were positive for overexpression (3+, n = 229, 23%; 2+, n = 135, 13%), a level that is greater than the 23% reported by Espinoza and Anguiano. We can not readily explain this difference. We still contend, however, that the Dako polyclonal antibody and the HercepTest seem to be more sensitive in formalin-fixed, paraffin-embedded tissue than previously available antibodies for HER2 immunohistochemistry. We believe that the 2+ (weakly positive) category is a manifestation of this increased sensitivity. Our concern with the HercepTest is related to the designation of 2+ staining as overexpression. Our findings in this regard are not unique. The United States Food and Drug Administration–approved package insert for HercepTest states that a result of 2+ on the HercepTest did not correlate well with the clinical trial assay (CTA), in that “approximately 42% of HercepTest 2+ results were negative by CTA (0-1).” We note in the fluorescence in situ hybridization (FISH) data of Espinoza and Anguiano that of the 21 cases that were positive with HercepTest, five (24%) were negative for HER2 amplification by FISH. We are completing our comparison of the HercepTest and HER2 gene amplification by FISH, and our preliminary results indicate that a 2+ result does not correlate with gene amplification. The relevant question that is still unanswered, however, is how well does the Herceptest predict response to Herceptin therapy. A clinical trial is currently under development in the North Central Cancer Treatment Group to determine the value of Herceptin in patients with 2+ staining.