The International BRCA1 /2Carrier Cohort Study: Purpose, Rationale, and Study Design

This is the authors' abstract. We don't add key points for this paper.

Breast cancer is the most common cancer affecting women in developed countries. Efforts to decrease breast cancer mortality have focused on early detection and improved treatment. Identification of women at particularly high risk of developing the disease provide a group on whom expensive and rigorous screening programs are cost-effective and a cohort of women who may benefit from trials of chemopreventive agents. The discovery of at least two genes which, when altered, confer markedly increased susceptibility to breast cancer has facilitated the identification of a cohort of individuals at particularly high risk of this disease. Although counseling and genetic testing of at-risk women is now underway in many centers in Europe and North America, the risks of cancer provided to gene carriers is based on limited data obtained from retrospective analyses in families largely selected for high incidence of living affected women. The same limitations apply to our knowledge of the risks of cancer at other sites and the possible interactions of these mutations with other genes and environmental effects (Phelan et al . 1996; Rebbeck et al . 1999; Brunet et al . 1998). These studies estimate a risk of breast cancer in female carriers of ~ 50% by age 50 and a ~ 80% lifetime risk (Easton et al . 1993; Easton et al . 1995; Ford et al . 1998). These two genes also predispose to an approximate 40% risk of ovarian cancer as well as 3 to 4-fold increased risks of colon ( BRCA1 ) and pancreatic cancer ( BRCA2 ) in both male and female carriers and prostate cancer ( BRCA1 and BRCA2 ) in men (Ford et al . 1994; Breast Cancer Linkage Consortium 1999). There have also been published reports that reproductive or other factors may alter the baseline risks conferred by BRCA1 alterations (Goldgar et al . 1995; Narod et al . 1995). Although prophylactic surgery is sometimes used as a means of prevention, there is little or no data regarding the efficacy of these procedures. 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 is a clear need for international coordination of these efforts with a standardized enrollment and follow-up protocol, and for combined data analyses.