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Originally published as JCO Early Release 10.1200/JCO.2008.20.7191 on December 15 2008 © 2009 American Society of Clinical Oncology.
In ReplyDepartments of Health Research and Policy and Medicine, Stanford University School of Medicine, Stanford, CA
Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA
Department of Medicine, Stanford University School of Medicine, Stanford, CA We appreciate the opportunity to respond to the letter by Chen et al regarding our recent article.1 Chen et al present a modified version of the BRCAPRO model (version 2.0-2), incorporating updated allele frequencies of BRCA1 and BRCA2 and reduced background incidence of breast and ovarian cancer in Asian-Americans who do not carry BRCA1/2 mutations. Per Table 1 of Chen et al, version 2.0-2 offers an improvement over the version we evaluated (1.2-1) in an independent cohort of Asian-Americans, particularly among those with at most 50% predicted probability of mutation carriage. We agree with the authors' conclusion that this modification to the BRCAPRO model may explain some portion of the difference which we observed. We also concur with the recommendation that a larger-scale validation study investigate how much of the underprediction we found in Asian-Americans is resolved by this change, versus by other potential causes such as differences in mutation prevalence or penetrance. Given that we observed similar underprediction by the Myriad II model as by BRCAPRO, we suggest that similar modifications to Myriad II may be justified to improve its performance in Asian-Americans.
Since people of Asian descent comprise a substantial proportion of the global population, further research on BRCA1/2 mutation epidemiology and predictive model performance in this racial/ethnic group remains a high priority. We thank Chen et al for their interesting and helpful response to our article, which may improve clinical BRCA1/2 mutation prediction among Asian-Americans. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Kurian AW, Gong GD, Chun NM, et al: Performance of BRCA1/2 prediction models in Asian-Americans. J Clin Oncol 26:4752–4758, 2008.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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