title: Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer.
abstract: 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.
authors.affiliation: 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.
authors.forename: Karin
authors.initials: K
authors.lastname: Kast
authors.affiliation: 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.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Rhiem
authors.affiliation: 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.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wappenschmidt
authors.affiliation: 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.
authors.forename: Eric
authors.initials: E
authors.lastname: Hahnen
authors.affiliation: 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Hauke
authors.affiliation: 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.
authors.forename: Britta
authors.initials: B
authors.lastname: Bluemcke
authors.affiliation: 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.
authors.forename: Verena
authors.initials: V
authors.lastname: Zarghooni
authors.affiliation: 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.
authors.forename: Natalie
authors.initials: N
authors.lastname: Herold
authors.affiliation: Department for Gynecology and Obstetrics, LMU Munich, Munich, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Ditsch
authors.affiliation: Department for Gynecology and Obstetrics, Technical University of Munich, Munich, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Kiechle
authors.affiliation: Breast Center, Department of Gynecology, Red Cross Hospital, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Braun
authors.affiliation: Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Fischer
authors.affiliation: Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Dikow
authors.affiliation: Department of Gynecology and Obstetrics, Heidelberg University Hospital, Heidelberg, Germany German Cancer Consortium (DKTK), NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schott
authors.affiliation: Medical Faculty, Institute of Human Genetics and Anthropology, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Rahner
authors.affiliation: Department of Gynecology and Obstetrics, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Niederacher
authors.affiliation: Department of Gynecology and Obstetrics, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.affiliation: Department of Human Genetics, University of Wuerzburg, Würzburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gehrig
authors.affiliation: Department of Human Genetics, University of Wuerzburg, Würzburg, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Mueller-Reible
authors.affiliation: Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Arnold
authors.affiliation: Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Maass
authors.affiliation: Institute of Human Genetics, University of Ulm, Ulm, Germany.
authors.forename: Guntram
authors.initials: G
authors.lastname: Borck
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital, Universität Ulm, Ulm, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: de Gregorio
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Scholz
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Auber
authors.affiliation: Institute of Medical and Human Genetics, Charite-University Medical Center, Berlin, Germany.
authors.forename: Raymonda
authors.initials: R
authors.lastname: Varon-Manteeva
authors.affiliation: Department of Gynecology, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Speiser
authors.affiliation: Institute for Human Genetics, University of Muenster, Münster, Germany.
authors.forename: Judit
authors.initials: J
authors.lastname: Horvath
authors.affiliation: Institute for Human Genetics, University of Muenster, Münster, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Lichey
authors.affiliation: 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.
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.affiliation: Department of Gynecology and Obstetrics, University of Leipzig, Leipzig, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Stark
authors.affiliation: Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tübingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Faust
authors.affiliation: Institute of Human Genetics, University of Regensburg, Regensburg, Germany.
authors.forename: Bernhard H F
authors.initials: BH
authors.lastname: Weber
authors.affiliation: Department of Obstetrics and Gynecology, University of Göttingen, Göttingen, Germany.
authors.forename: Gunter
authors.initials: G
authors.lastname: Emons
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Zachariae
authors.affiliation: Department for Gynecology and Obstetrics, Technical University of Munich, Munich, Germany.
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.affiliation: 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.
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Engel
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D015995:Prevalence
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA1; BRCA2; Mutation prevalences; risk criteria