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Original article
Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer
  1. Karin Kast1,2,
  2. Kerstin Rhiem3,
  3. Barbara Wappenschmidt3,
  4. Eric Hahnen3,
  5. Jan Hauke3,
  6. Britta Bluemcke3,
  7. Verena Zarghooni3,
  8. Natalie Herold3,
  9. Nina Ditsch4,
  10. Marion Kiechle5,
  11. Michael Braun6,
  12. Christine Fischer7,
  13. Nicola Dikow7,
  14. Sarah Schott8,9,
  15. Nils Rahner10,
  16. Dieter Niederacher11,
  17. Tanja Fehm11,
  18. Andrea Gehrig12,
  19. Clemens Mueller-Reible12,
  20. Norbert Arnold13,
  21. Nicolai Maass13,
  22. Guntram Borck14,
  23. Nikolaus de Gregorio15,
  24. Caroline Scholz16,
  25. Bernd Auber16,
  26. Raymonda Varon-Manteeva17,
  27. Dorothee Speiser18,
  28. Judit Horvath19,
  29. Nadine Lichey19,
  30. Pauline Wimberger1,2,
  31. Sylvia Stark20,
  32. Ulrike Faust21,
  33. Bernhard H F Weber22,
  34. Gunter Emons23,
  35. Silke Zachariae24,
  36. Alfons Meindl5,
  37. Rita K Schmutzler3,
  38. Christoph Engel24
  39. on behalf of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC)
  1. 1Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
  2. 2German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany
  3. 3Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO) and Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany
  4. 4Department for Gynecology and Obstetrics, LMU Munich, Munich, Germany
  5. 5Department for Gynecology and Obstetrics, Technical University of Munich, Munich, Germany
  6. 6Breast Center, Department of Gynecology, Red Cross Hospital, Munich, Germany
  7. 7Institute of Human Genetics, Heidelberg University, Heidelberg, Germany
  8. 8Department of Gynecology and Obstetrics, Heidelberg University Hospital, Heidelberg, Germany
  9. 9German Cancer Consortium (DKTK), NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany
  10. 10Medical Faculty, Institute of Human Genetics and Anthropology, Heinrich-Heine University, Düsseldorf, Germany
  11. 11Department of Gynecology and Obstetrics, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
  12. 12Department of Human Genetics, University of Wuerzburg, Würzburg, Germany
  13. 13Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany
  14. 14Institute of Human Genetics, University of Ulm, Ulm, Germany
  15. 15Department of Gynecology and Obstetrics, University Hospital, Universität Ulm, Ulm, Germany
  16. 16Institute of Human Genetics, Hannover Medical School, Hannover, Germany
  17. 17Institute of Medical and Human Genetics, Charite-University Medical Center, Berlin, Germany
  18. 18Department of Gynecology, Charité University Medicine Berlin, Berlin, Germany
  19. 19Institute for Human Genetics, University of Muenster, Münster, Germany
  20. 20Department of Gynecology and Obstetrics, University of Leipzig, Leipzig, Germany
  21. 21Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tübingen, Germany
  22. 22Institute of Human Genetics, University of Regensburg, Regensburg, Germany
  23. 23Department of Obstetrics and Gynecology, University of Göttingen, Göttingen, Germany
  24. 24Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
  1. Correspondence to Karin Kast, Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, TU Dresden, Fetscherstraße 74, Dresden 01069, Germany; karin.kast{at}


Purpose To characterise the prevalence of pathogenic germline mutations in BRCA1 and BRCA2 in families with breast cancer (BC) and ovarian cancer (OC) history.

Patients and methods Data from 21 401 families were gathered between 1996 and 2014 in a clinical setting in the German Consortium for Hereditary Breast and Ovarian Cancer, comprising full pedigrees with cancer status of all individual members at the time of first counselling, and BRCA1/2 mutation status of the index patient.

Results The overall BRCA1/2 mutation prevalence was 24.0% (95% CI 23.4% to 24.6%). Highest mutation frequencies were observed in families with at least two OCs (41.9%, 95% CI 36.1% to 48.0%) and families with at least one breast and one OC (41.6%, 95% CI 40.3% to 43.0%), followed by male BC with at least one female BC or OC (35.8%; 95% CI 32.2% to 39.6%). In families with a single case of early BC (<36 years), mutations were found in 13.7% (95% CI 11.9% to 15.7%). Postmenopausal unilateral or bilateral BC did not increase the probability of mutation detection. Occurrence of premenopausal BC and OC in the same woman led to higher mutation frequencies compared with the occurrence of these two cancers in different individuals (49.0%; 95% CI 41.0% to 57.0% vs 31.5%; 95% CI 28.0% to 35.2%).

Conclusions Our data provide guidance for healthcare professionals and decision-makers to identify individuals who should undergo genetic testing for hereditary breast and ovarian cancer. Moreover, it supports informed decision-making of counselees on the uptake of genetic testing.

  • Mutation prevalences
  • BRCA1
  • BRCA2
  • risk criteria

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