Context: The distribution of BRCA1 and BRCA2 mutations in women diagnosed with noninvasive breast carcinoma is unknown.
Objective: To estimate the BRCA1 and BRCA2 mutation prevalence in women with ductal carcinoma in situ (DCIS), unselected for age, family history, or ethnicity.
Design, setting, and participants: The data were 369 DCIS cases diagnosed among female residents aged 20 to 79 years from the state of Connecticut between September 15, 1994, and March 14, 1998. These women were participants in a large population-based case-control study of breast carcinoma in situ. Telephone interviews were used to collect risk factor information and blood or buccal specimens were collected for BRCA1 and BRCA2 mutation testing.
Main outcome measures: Prevalence of disease-associated mutations of BRCA1 and BRCA2 in women diagnosed with DCIS.
Results: Three (0.8%) and 9 (2.4%) of 369 DCIS cases had disease-associated mutations in BRCA1 or BRCA2, respectively. One woman had a mutation in both genes (BRCA1 W321X and BRCA2 3398del5). Carriers were significantly more likely than noncarriers to report a first-degree (mother, sister, or daughter) family history of breast cancer (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.1-12.4), as well as a personal history of ovarian cancer. In addition, carriers were more likely than noncarriers to be diagnosed at an early age (<50 years) (OR, 3.4; 95% CI, 1.0-11.7), as well as to report at least 1 first-degree relative diagnosed with breast cancer before 50 years (OR, 10.6; 95% CI, 3.0-37.0).
Conclusions: Ductal carcinoma in situ is a part of the breast/ovarian cancer syndromes defined by BRCA1 and BRCA2, with mutation rates similar to those found for invasive breast cancer. These findings suggest that patients with breast cancer with an appropriate personal or family history of breast and/or ovarian cancer should be screened and followed according to high-risk protocols, regardless of whether they are diagnosed with in situ or invasive breast cancer.