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Originally published as JCO Early Release 10.1200/JCO.2008.16.8310 on September 8 2008 © 2008 American Society of Clinical Oncology. Performance of BRCA1/2 Mutation Prediction Models in Asian Americans
From the Departments of Medicine, Health Research and Policy, and Genetics, Stanford University School of Medicine, Stanford; Department of Medicine, University of California at San Francisco, San Francisco, CA; Department of Medical Genetics, The Queen's Medical Center, Honolulu, HI; and the Hereditary Cancer Program, British Columbia Cancer Agency, Vancouver, British Columbia, Canada Corresponding author: Allison W. Kurian, MD, MSc, Stanford University School of Medicine, HRP Redwood Building, Room T254A, Stanford, CA 94305-5405; e-mail: akurian{at}stanford.edu Purpose There are established differences in breast cancer epidemiology between Asian and white individuals, but little is known about hereditary breast cancer in Asian populations. Although increasing numbers of Asian individuals are clinically tested for BRCA1/2 mutations, it is not known whether computer models that predict mutations work accurately in Asian individuals. We compared the performance in Asian and white individuals of two widely used BRCA1/2 mutation prediction models, BRCAPRO and Myriad II. Patients and Methods We evaluated BRCAPRO and Myriad II in 200 Asian individuals and a matched control group of 200 white individuals who were tested for BRCA1/2 mutations at four cancer genetics clinics, by comparing numbers of observed versus predicted mutation carriers and by evaluating area under the receiver operating characteristic curve (AUC) for each model.
Results BRCAPRO and Myriad II accurately predicted the number of white BRCA1/2 mutation carriers (25 observed v 24 predicted by BRCAPRO; 25 predicted by Myriad II, P Conclusion Both BRCAPRO and Myriad II underestimated the proportion of BRCA1/2 mutation carriers, and discriminated carriers from noncarriers less well, in Asian compared with white individuals. published online ahead of print at www.jco.org on September 8, 2008 Supported by Susan G. Komen Breast Cancer Research Foundation Award No. POP0503911 and National Institutes of Health K12 Building Interdisciplinary Research Careers in Women's Health Award No. HD043452. Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL. Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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.69), but underpredicted Asian carriers by two-fold (49 observed v 25 predicted by BRCAPRO; 26 predicted by Myriad II; P 
3 x 10–7). For BRCAPRO, this racial difference reflects substantial underprediction of Asian BRCA2 mutation carriers (26 observed v 4 predicted; P = 1 x 10–30); for Myriad II, separate mutation predictions were not available. For both models, AUCs were nonsignificantly lower in Asian than white individuals, suggesting less accurate discrimination between Asian carriers and noncarriers. 
