Family history of breast and ovarian cancer and the risk of breast carcinoma in situ

A family history of breast cancer is an important risk factor for breast carcinoma in situ (BCIS), however, there are no detailed analyses of its variation in effect by number, type, laterality or age at onset of affected relatives nor by association with ovarian cancer. In addition, the role of the breast cancer susceptibility genes, BRCA1 and BRCA2, in the development of BCIS is unclear. Objective. To better define the role of: (1) a family history of breast and ovarian cancer and (2) the cancer susceptibility genes, BRCA1 and BRCA2, in the development of BCIS. Methods. The data are 875 ductal carcinoma in situ (DCIS) and 123 lobular carcinoma in situ (LCIS) cases diagnosed among residents of the state of Connecticut from September 15, 1994 to March 14, 1998 and between the age of 20 and 79 years. Controls (n = 999 are female Connecticut residents collected via random-digit-dial and frequency matched to the cases by 5-year age intervals. Telephone interviews were used to collect information on risk factors and cancer screening history. Logistic regression was used to provide maximum likelihood estimates of the odds ratios (OR) with 95% confidence intervals (95% CI). The probability of being a BRCA1 and/or BRCA2 gene carrier was calculated for each case and control, using family history of breast and ovarian cancer, age/age at diagnosis for relatives, prevalence and penetrance data for BRCA1/BRCA2, and self-report of Jewish heritage. Results. Cases with DCIS or LCIS were significantly more likely to report a first degree family history of breast cancer (OR: 1.6, 95% CI: 1.3, 2.1 and 1.8, 95% CI: 1.2, 2.9, respectively) than were controls. In addition, DCIS cases were 2.4 (95% CI: 0.8, 7.2) times more likely than controls to report both an affected mother and sister. An inverse association was suggested between age at onset and DCIS risk with cases aged 49 years or younger at 2.1 (95% CI: 1.3, 3.4) times the risk of controls (95% CI) versus 1.5 (95% CI: 1.1, 2.0) for cases older than 49 years. An elevated risk of DCIS was associated with a family history of ovarian cancer but did not reach statistical significance (OR: 1.3, 95% CI: 0.7, 2.5). Approximately 3.7% and 1.9% of DCIS cases were predicted to carry a mutation in BRCA1 and BRCA2, respectively. Conclusions. A family history of breast cancer is associated with an increased risk of DCIS and LCIS, particularly among women with multiple relatives affected at early ages. Statistical risk models predict a low prevalence rate of BRCA1 and BRCA2 in DCIS; these estimates await confirmation through laboratory testing.