BRCA in breast cancer: ESMO clinical recommendations.

Familial susceptibility to breast cancer accounts for 25% of all breast cancer cases. In familial breast cancer, mutations in the BRCA1, BRCA2, CHEK2, TP53 and PTEN genes account for 5–10% of breast and ovarian cancer cases overall. The prevalence of BRCA1 or BRCA2 mutations varies considerably between ethnic groups and geographical areas. Populationspecific mutations have been described in Iceland, the Netherlands, Sweden, Norway, Germany, France, Spain, countries of central and eastern Europe and among Ashkenazi Jews. The prevalence of BRCA mutation carriers in the general population is estimated at between 1/800 and 1/1000. BRCA1 and BRCA2 mutation frequencies in breast and ovarian cancer patients unselected for family history or age at onset are generally low (<1–7% for BRCA1 and 1–3% for BRCA2). Higher prevalence is associated with a family history of breast or ovarian cancer, young age at onset, male breast cancer or multiple tumors (bilateral breast cancer or breast and ovarian cancer in the same patient). Women with an inherited BRCA1 mutation have a lifetime risk of 65–80% of developing breast cancer and 37–62% of developing ovarian cancer, while BRCA2 mutation carriers have a lifetime risk of 45–85% for breast cancer and 11–23% for ovarian cancer. There is an increased risk of prostate cancer among BRCA carriers (5–25%) and breast cancer among males with BRCA2 mutations (6%). Other cancers at increased risk are pancreatic (up to 2%), stomach, and head and neck.