The International BRCA1/2 Carrier Cohort Study (IBCCS)


Breast cancer is the most common cancer affecting women in developed countries. Germ line mutations in the BRCA1 and BRCA2 genes confer high lifetime risks of breast and ovarian cancer. In population based studies, the risk of breast cancer by age 70 has been estimated to be about 65% in BRCA1 mutation carriers and 45% in BRCA2 carriers. Many other risk factors for breast cancer are known, however, and an important unresolved question is the extent to which other risk factors modify the cancer risk in carriers.
While several countries have begun national or regional efforts to address these issues prospectively, the sample sizes required for adequate precision of risk estimates and power for detection of risk modification are often beyond the scope of any one center. Accordingly, there was a clear need for international coordination of these efforts with a standardized enrollment and follow-up protocol, and for combined data analyses.
The IBCCS was initiated in 1997 as a collaborative European study of women carrying a deleterious mutation in BRCA1 or BRCA2. The general purpose of this study is to estimate prospectively the risks of breast, ovarian, and other cancers in BRCA1 and BRCA2 (BRCA1/2) carriers and to assess lifestyle and genetic factors that may modify the cancer risks.
 Specific aims:
  1. more precisely estimate the age-, sex-, and site-specific cancer risks due to mutations in the BRCA1 and BRCA2 genes;
  2. assess the importance of risk factors as known in the general population, in determining the cancer risks in the BRCA1/2 mutation carriers;
  3. examine the efficacy of prophylactic surgery and other screening/prevention options in these high risk women;
  4. create an ongoing registry of gene carriers for potential use in future clinical trials
The knowledge gained from this prospective observational study will allow family cancer clinics in each country to provide more accurate risk information to women who are found to be gene carriers. Thus, BRCA1/2 mutation carriers may make more informed choices regarding their options for prevention and screening.
Subjects eligible for the IBCCS must be a carrier of a mutation in either BRCA1 or BRCA2. This includes women who have been diagnosed with cancer (at any site) and those who are currently unaffected, as well as male gene carriers. In addition, they must be more than 18 years of age, mentally capable, and must have been counseled about their mutation status.
The data for the IBCCS is collected at different centers in 15 countries. Dr. David Goldgar started the coordination of the study at the International Agency of Cancer Research (IARC) in Lyon, France. From 2008 onwards Dr. Matti Rookus (m.rookus@nki.nl) coordinates the study at the Netherlands Cancer Institute (NKI) in the Netherlands (data manager: Thea Mooij, MSc, ibccs@nki.nl).