title: The penetrance of ductal carcinoma in situ among BRCA1 and BRCA2 mutation carriers.
abstract: Ductal carcinoma in situ (DCIS) is a precancerous lesion of the female breast and is strongly suspected to be a precursor of invasive breast cancer (IBC). Our goal is the estimation of the age-specific and lifetime penetrances of DCIS among carriers of either a BRCA1 or BRCA2 deleterious mutation. We jointly re-analyze the SEER9 database and a previous study by Claus et al. (JAMA 293:964-969, 2005). Estimation is performed via Bayes theorem after the evaluation of the ratio of age-specific DCIS incidences, and extrapolation to the general population of the study-specific penetrance obtained from Claus et al. From the SEER9 database, we estimate the lifetime risk of DCIS to be 0.98 %, in contrast to value of 12.5 % usually reported for IBC. By extending the result in Claus et al. to the general population, we obtain a lifetime risk for carriers of a deleterious mutation of either BRCA1 or BRCA2 of 6.21 % (95 % CI 6.09-6.33 %). The increase in lifetime risk of DCIS for a BRCA mutation carrier compared to a non-carrier is therefore about six-fold. Our quantification is directly relevant to the identification and genetic counseling of BRCA mutation carriers, and emphasizes the potential importance of including information on diagnoses of DCIS in counseling of individuals who are at familial risk for breast cancer. All these factors can contribute to a more specific and targeted prevention, potentially reducing the impact of IBC among BRCA mutation carriers.
authors.affiliation: Department of Biostatistics, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215-5450, USA. mazzola@jimmy.harvard.edu
authors.forename: Emanuele
authors.initials: E
authors.lastname: Mazzola
authors.forename: Su-Chun
authors.initials: SC
authors.lastname: Cheng
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parmigiani
mesh_terms: D000328:Adult; D000368:Aged; D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000235:genetics*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D019683:Penetrance; D012189:Retrospective Studies; D012306:Risk; D018426:SEER Program; D055815:Young Adult