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Journal of Clinical Oncology, Vol 25, No 22 (August 1), 2007: pp. 3383-a-3384 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.12.3489
One Risk Fits All?Department of Epidemiology, Department of Gynaecology, Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands To the Editor: In the April 10, 2007, issue of the Journal of Clinical Oncology, Chen and Parmigiani present a set of cancer risk estimates for counseling and management of BRCA1 and BRCA2 mutation carriers.1 Based on 10 very different studies regarding the inclusion of patients, the authors calculated overall estimates for mean cumulative cancer risks at age 70. Though the authors observed significant between-study heterogeneity and discussed several possible sources, they could not explain it. We have two concerns regarding the presented risk tables. First, the studied populations included in the meta-analysis are very heterogeneous indeed, comprising very high-risk research families (Breast Cancer Linkage Consortium) as well as high-risk families ascertained through familial cancer clinics and also cases with Ashkenazi-based populations. In doing so, the obtained data will actually be applicable to neither of these groups nor to the population that attend family cancer clinics and are in need of tailored risk figures for counseling and management. Second, ever since the first reports on cancer risks in BRCA1 and BRCA2 mutation carriers, the penetrance figures show an overall decreasing trend in subsequent studies. This is partly due to the fact that initial families that came for counseling were very strongly affected and to the fact that inclusion criteria for genetic testing have become less strict over the last decade. Indeed, in the manuscript it is mentioned that the three most recent familial cancer clinic–based studies on the penetrance of BRCA1 and BRCA2 mutations have lower risk estimates.2-4 These studies seem to come closest to the current setting of familial cancer clinic counseling; therefore, we suggest that the included studies should not only be stratified by ascertainment, but also by year of publication. Up-to-date cancer risk tables for BRCA1 and BRCA2 are definitely needed for counseling and management, but we suggest that we should further explore and not pool the sources of heterogeneity and variation in penetrance. By doing so, we can make cancer risk tables more population-specific with respect to sources of heterogeneity—such as ascertainment, ethnic background, family history, and possibly genotype—to facilitate tailored risk counseling. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Chen S, Parmigiani G: Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25:1329-1333, 2007 2. Scott CL, Jenkins MA, Southey MC, et al: Average age-specific cumulative risk of breast cancer according to type and site of germline mutations in BRCA1 and BRCA2 estimated from multiple-case breast cancer families attending Australian family cancer clinics. Hum Genet 112:542-551, 2003[CrossRef][Medline] 3. Marroni F, Aretini P, D'Andrea E, et al: Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations. Eur J Hum Genet 12:899-906, 2004[CrossRef][Medline] 4. Chen S, Iversen ES, Friebel T, et al: Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol 24:3312-3313, 2006 Related Reply
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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