Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer.

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

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.

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%).

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.

Journal of medical genetics. 2016 Jan 29 [Epub]

Karin Kast, Kerstin Rhiem, Barbara Wappenschmidt, Eric Hahnen, Jan Hauke, Britta Bluemcke, Verena Zarghooni, Natalie Herold, Nina Ditsch, Marion Kiechle, Michael Braun, Christine Fischer, Nicola Dikow, Sarah Schott, Nils Rahner, Dieter Niederacher, Tanja Fehm, Andrea Gehrig, Clemens Mueller-Reible, Norbert Arnold, Nicolai Maass, Guntram Borck, Nikolaus de Gregorio, Caroline Scholz, Bernd Auber, Raymonda Varon-Manteeva, Dorothee Speiser, Judit Horvath, Nadine Lichey, Pauline Wimberger, Sylvia Stark, Ulrike Faust, Bernhard H F Weber, Gunter Emons, Silke Zachariae, Alfons Meindl, Rita K Schmutzler, Christoph Engel, German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC)

Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany., Center 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., Department for Gynecology and Obstetrics, LMU Munich, Munich, Germany., Department for Gynecology and Obstetrics, Technical University of Munich, Munich, Germany., Breast Center, Department of Gynecology, Red Cross Hospital, Munich, Germany., Institute of Human Genetics, Heidelberg University, Heidelberg, Germany., Department of Gynecology and Obstetrics, Heidelberg University Hospital, Heidelberg, Germany German Cancer Consortium (DKTK), NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany., Medical Faculty, Institute of Human Genetics and Anthropology, Heinrich-Heine University, Düsseldorf, Germany., Department of Gynecology and Obstetrics, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Department of Human Genetics, University of Wuerzburg, Würzburg, Germany., Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany., Institute of Human Genetics, University of Ulm, Ulm, Germany., Department of Gynecology and Obstetrics, University Hospital, Universität Ulm, Ulm, Germany., Institute of Human Genetics, Hannover Medical School, Hannover, Germany., Institute of Medical and Human Genetics, Charite-University Medical Center, Berlin, Germany., Department of Gynecology, Charité University Medicine Berlin, Berlin, Germany., Institute for Human Genetics, University of Muenster, Münster, Germany., Department of Gynecology and Obstetrics, University of Leipzig, Leipzig, Germany., Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tübingen, Germany., Institute of Human Genetics, University of Regensburg, Regensburg, Germany., Department of Obstetrics and Gynecology, University of Göttingen, Göttingen, Germany., Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.