Specificity of HercepTest in determining HER-2/neu status of breast cancers using the united states food and drug administration-approved scoring system

Purpose: To evaluate the specificity of the HercepTest for Immunoenzymatic Staining (Dako Corp, Carpinteria, CA) for determining HER-2/neu protein exp ression in breast cancer. Materials and Methods: Forty-eight invasive breast cancers previously found to be HER-S/neu-negative by two different immunohistochemical (IHC) assays and not amplified for the HER-S/neu gene by fluorescence in situ hybridiza tion were studied using the HercepTest kit. HercepTest was performed accord ing to the manufacturer's guidelines, and the results were scored on a 0 to 3+ scale using the United States Food and Drug Administration (FDA)-approv ed grading system. In this system, cases scored as 2+ or 3+ are considered HER-S/neu-positive. Results: Among these 48 cases, the IHC score using the FDA-approved scaring system wets 0 in four cases (8.3%), 1+ in 16 (33.3%), 2+ in 21 (43.8%), an d 3+ in seven (14.6%), Therefore, 58.4% of these cases were categorized as HER-2/neu-positive, and the specificity of the HercepTest kit for HER-2/neu expression was 41.6%. However, with the use of a modified scaring system t hat took into account the level of staining of nonneoplastic epithelium, th e specificity increased to 93.2%. Conclusion: Our results indicate that the HercepTest kit, when used in acco rdance with the manufacturer's guidelines and the FDA-approved scoring syst em, results in a large proportion of breast cancers being categorized as po sitive for HER-2/neu protein expression and that many of these seem to be f alse-positives. Consideration of the level of staining of nonneoplastic epi thelium resulted in improved specificity. The current FDA-approved scoring system for HercepTest results should be reevaluated before its widespread u se in clinical practice. (C) 1999 by American Society of Clinical Oncology.