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.
References
Struewing JP, Hartge P, Wacholder S et al (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336(20):1401–1408
Ford D, Easton DF, Bishop DT et al (1994) Breast Cancer Linkage Consortium: risks of cancer in BRCA1 mutation carriers. Lancet 343(8899):692–695
Easton DF, Ford D (1995) Bishop DT Breast and ovarian cancer incidence in BRCA1 mutation carriers: Breast Linkage Consortium. Am J Hum Genet 56(1):265–271
Ford D, Easton DF, Stratton M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families: the Breast Cancer Linkage Consortium. Am J Hum Genet 62(3):676–689
Thorlacius S, Struewing JP, Hartge P et al (1998) Population-based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet 352:1337–1339
King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Sci Agric 302:643–646
Begg CB, Haile RW, Borg A et al (2008) Variation of breast cancer risk among BRCA1/2 carriers. JAMA 299(2):194–201
Claus EB, Petruzella S, Matloff E et al (2005) Prevalence of BRCA1 and BRCA2 mutations in women diagnosed with ductal carcinoma in situ. JAMA 293(8):964–969
Frank TS, Deffenbaugh AM, Reid JE et al (2002) Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol 20(6):1480–1490
Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25(11):1329–1333
Parmigiani G, Berry DA, Aguilar O (1998) Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. Am J Hum Genet 62:145–158
Antoniou AC, Pharoah PP, Smith P et al (2004) The BOADICEA model of genetic susceptibility to breast and ovarian cancer. Br J Cancer 91:1580–1590
Tyrer J, Duffy SW, Cuzick J (2004) A breast cancer prediction model incorporating familial and personal risk factors. Stat Med 23:1111–1130
Altekruse SF, Kosary CL, Krapcho M et al (2010) SEER cancer statistics review, 1975–2007. NCI, Bethesda
Cheng S, Wang W, Broman KW et al (2004) BayesMendel: an R environment for Mendelian risk prediction. Stat Appl Genet Mol Biol 3(1):article 21
Acknowledgments
This work was supported by the Susan G Komen Breast Cancer Foundation (KG081303) and by the NCI comprehensive cancer center core grant 5P30 CA006516-46.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mazzola, E., Cheng, SC. & Parmigiani, G. The penetrance of ductal carcinoma in situ among BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat 137, 315–318 (2013). https://doi.org/10.1007/s10549-012-2345-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-012-2345-5