Mutations in the BRCA1 gene result in an elevated risk of breast cancer (BC) and ovarian cancer (OC). However, risk estimates vary depending on the study population and statistical methodology used, and there are indications that the birth cohort and location of the mutation influence cancer risk. We investigated the risks for BC and OC associated with BRCA1 mutations in a young cohort of female mutation carriers who were identified by molecular genetic testing and belonged to a genetically heterogeneous Central European population. The study included 106 healthy and 158 affected carriers identified at an Austrian risk evaluation center. Risk estimation employed the product limit method. The log rank test was used to compare different strata. The risk of developing cancer to age 70 was found to be 85% for BC (95% CI 75-97%) and 53% for OC (95% CI 37-68%). Female mutation carriers born in 1958 or later were subject to a significantly higher risk of BC (P=0.005; 27% vs. 46% to age 40) and OC (P=0.006; 2% vs. 8% to age 40) than those born earlier. Mutations in exon 11 were associated with lower BC risk than mutations in exons 1-10 (P=0.008) and exons 12-24 (P=0.0006). OC risk was not influenced by mutation location (P=0.86). We conclude that female BRCA1 mutation carriers should be counseled about their cohort-dependent cancer risk. Further research into variables that affect cancer risk and are amenable to modification (e.g., lifestyle-related factors) should be considered a priority.

BRCA1 mutation carriers should be informed of the fact that pre-malignant and even malignant changes are frequently found in PM specimens despite normal radiological findings.

Mutations in the BRCA1 or BRCA2 genes result in a significantly increased risk of breast and ovarian cancer. Austrian women who carry a BRCA1 mutation have a risk of 85% for breast cancer and 53% for ovarian cancer up to 70 years of age. At-risk women have 2 medical options: closely monitored early detection using mammography, breast ultrasound, and MRI, as well as tumor markers and vaginal ultrasound, or real risk reduction through prophylactic removal of the breast tissue and/or the ovaries. As awareness of such a high risk of disease may cause a great deal of distress, and because prophylactic surgeries offer only very drastic measures for risk reduction, a special multidisciplinary care concept is of particular importance. This care starts with comprehensive genetic counseling before performing molecular genetic analysis and must be continued after a genetic predisposition for breast and ovarian cancer has been identified. Right from the start, special schooling in Austria has ensured that patients in all cooperating genetic counseling centers are counseled, selected, and followed- up according to the same criteria.