Assessment of HER2 testing patterns, HER2+ disease, and the utilization of HER2-directed therapy in early breast cancer

Abstract

David D Stenehjem,1,2 Minkyoung Yoo,1 Sudhir K Unni,1 Mukul Singhal,1 Hillevi Bauer,1 Kim Saverno,1 Cheng Quah,3 Anthony Masaquel,3 Diana I Brixner1,41Pharmacotherapy Outcomes Research Center (PORC), College of Pharmacy, University of Utah, Salt Lake City, UT, USA; 2Huntsman Cancer Institute, Salt Lake City, UT, USA; 3Genentech, Inc., South San Francisco, CA, USA; 4Program in Personalized Health Care, University of Utah, Salt Lake City, UT, USAContext: Determining human epidermal growth factor receptor 2 (HER2) status is critical for the management of early-stage breast cancer (ESBC). An understanding of HER2 testing practices can provide insight into how test results influence the use of HER2-directed therapy.Objective: To assess HER2 testing, HER2+ disease, and HER2-directed therapy in ESBC at the Huntsman Cancer Institute before and after the 2007 American Society of Clinical Oncology and College of American Pathologist (ASCO/CAP) guidelines on HER2 testing were published.Methods: Patients were identified from an institutional tumor registry. HER2 testing patterns and results were examined using a chart review of pathology and clinical notes. Patient characteristics, HER2+ rate, and trastuzumab use were evaluated descriptively. Discordance rate with reflex testing (immunohistochemistry [IHC]2+ retested by fluorescence in situ hybridization [FISH]) was also evaluated.Results: A total of 1,459 women were included (mean age: 57 years). The rate of HER2+ disease was 17% (number [N] =245). The discordance rate between IHC2+ and FISH was 10%. After the 2007 ASCO/CAP guidelines, fewer tumors were classified as IHC3+ (16% post- versus 21.9% pre-2007), more tumors were characterized as IHC2+ (26.4% post- versus 20.7% pre-2007), and the overall HER2+ rate was decreased (18.7% versus 21.9%), but this was not statistically significant (P=0.519). Most patients with HER2+ ESBC received HER2-targeted therapy (N=185).Conclusion: The HER2+ rate was 17% and within the range of the reported rates in the literature. Reflex testing identified additional HER2+ tumors by approximately 10%, and should be considered a potential quality indicator. ASCO/CAP HER2 testing guidelines in 2007 appeared to impact the interpretation and classification of HER2+ tumors.Keywords: human epidermal growth factor receptor 2, HER2, early-stage breast cancer, immunohistochemistry, FISH, HER2-targeted therapy