Geburtshilfe Frauenheilkd 2016; 76 - P079
DOI: 10.1055/s-0036-1592705

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

S Kommoss 1, P Harter 2, J Hauke 3, F Heitz 2, A Reuss 4, F Marmé 5, A Heimbach 3, K Prieske 6, L Richters 3, A Burges 7, G Neidhardt 3, N de Gregorio 8, A El-Balat 9, F Hilpert 10, W Meier 11, M Heubner 12, K Kast 13, I Braicu 14, E Hahnen 3, R Schmutzler 3
  • 1Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland
  • 2Kliniken Essen-Mitte (KEM), Essen, Deutschland
  • 3Universitätsklinikum Köln, Zentrum Familiärer Brust- und Eierstockkrebs, Köln, Deutschland
  • 4Universität Marburg, Koordinierungszentrums für klinische Studien, Marburg, Deutschland
  • 5Nationales Zentrum für Tumorerkrankungen, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
  • 6Universitätsklinikum Hamburg-Eppendorf, Abteilung für Gynäkologie und Gynäkologische Onkologie, Hamburg, Deutschland
  • 7Klinikum der Universität München – Großhadern, Klinik für Frauenheilkunde und Geburtshilfe, München, Deutschland
  • 8Universitätsklinikum Ulm, Frauenklinik, Ulm, Deutschland
  • 9Universitätsklinikum Frankfurt, Frauenheilkunde und Geburtshilfe, Frankfurt a.M., Deutschland
  • 10Onkologisches Therapiezentrum am Krankenhaus Jerusalem, Hamburg, Deutschland
  • 11Evangelisches Krankenhaus Düsseldorf, Frauenklinik, Düsseldorf, Deutschland
  • 12Universitätsklinikum Essen, Frauenklinik, Essen, Deutschland
  • 13Universitätsklinikum Dresden, Abteilung für Frauenheilkunde und Geburtshilfe, Dresden, Deutschland
  • 14Charité, Campus Virchow Klinikum, Klinik für Frauenheilkunde, Berlin, Deutschland

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.