Prevalence of BRCA1 and BRCA2 Mutations in Women Diagnosed With Ductal Carcinoma In Situ

THERE EXISTS AN EVER-ENLARGing literature on the prevalence of disease-associated mutations in 2 breast cancer susceptibility genes, BRCA1 and BRCA2, among women diagnosed with invasive breast cancer (IBC). Estimates of mutation rates are currently available for a number of population-based as well as high-risk groups, including women of Ashkenazi Jewish background or women with multiple family members diagnosed with breast or ovarian cancer. Studies of mutation rates among IBC cases in the general population (among women unselected for family history or ethnicity) exist for a variety of ages at onset. The most recent analyses place the prevalence of BRCA1 and BRCA2 mutations among all women diagnosed with IBC at between 0.4% to 2.6% and 1.4% to 1.5%, respectively, combined across all age groups. Carrier prevalence estimates in population-based IBC cases diagnosed at an early age ( 45 years) are generally higher and range from 1.9% to 7.5% for BRCA1 and 2.2% to 2.7% for BRCA2, with estimates for BRCA2 varying less with age than those for BRCA1. Estimates of mutation rates in high-risk groups are markedly higher, including a rate of approximately 20% associated with the BRCA1 185delAG mutation among Ashkenazi Jewish women with IBC diagnosed before 42 years and a rate of 24% associated with the BRCA2 999del5 mutation in Icelandic women diagnosed with IBC before 40 years. Controversy exists regarding the role of ductal carcinoma in situ (DCIS) with Author Affiliations: Department of Epidemiology and Public Health (Dr Claus and Ms Petruzella), Yale Comprehensive Cancer Center (Ms Matloff ), and Department of Pathology (Dr Carter), Yale University School of Medicine, New Haven, Conn; and Department of Neurosurgery, Brigham and Women’s Hospital, Boston, Mass (Dr Claus). Corresponding Author: Elizabeth B. Claus, MD, PhD, Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St, PO Box 208034, New Haven, CT 06520-8034 (elizabeth.claus @yale.edu). Context The distribution of BRCA1 and BRCA2 mutations in women diagnosed with noninvasive breast carcinoma is unknown.