Incidence of germline mutations in risk genes including BRCA1/2 in consecutive ovarian cancer (OC) patients (AGO TR-1)

Background: Identification of families at risk for OC including recommendation for prophylactic surgery is the only effective method to reduce OC mortality. In addition, BRCA1/2 mutations are known as prognostic factor and target for treatment. Methods: Prospective counseling and testing of consecutive patients with first diagnosis or platinum sensitive relapse of invasive epithelial OC. Testing of 25 risk genes related to ovarian cancer. A positive mutation was defined as class 4/5 mutation and a positive family history was defined as at least one relative with breast cancer (BC) or OC or BC in personal history. Results: In total, 529 pts entered the study, of which 507 were analyzed so far: 270 (53%) patients with first diagnosis of OC and 237 (47%) patients with platinum sensitive relapse. In total, 21% were BRCA1 / 2 positive ( BRCA positive) and 27% for a mutation in at least one risk gene. The incidence of mutations in BRCA1 was 15%, BRCA2 : 6%, RAD51C : 1.8%, PALB2 : 1.2%. Mutations in all others were found less frequently (< 1%). In elderly patients (> 70 years), 13% carried a mutation in a risk gene compared to 31% of patients ≤70 years (p < 0.001). Family history identified 69% of the BRCA1/2 positive patients, but missed 31%. Conclusions: 27% of all OC pts harbor a positive mutation in the genes analyzed. Age and FH are insufficient for identifying these patients. Genetic testing should therefore be offered to every patient with invasive epithelial ovarian cancer; limiting testing to BRCA1/2 analysis seems insufficient.