title: BRCA1 and BRCA2 mutation status and cancer family history of Danish women affected with multifocal or bilateral breast cancer at a young age.
abstract: BACKGROUND
  A small fraction of breast cancer is the result of germline mutations in the BRCA1 and BRCA2 cancer susceptibility genes. Mutation carriers frequently have a positive family history of breast and ovarian cancer, are often diagnosed at a young age, and may have a higher incidence of double or multiple primary breast tumours than breast cancer patients in general.
  
  
  OBJECTIVE
  To estimate the prevalence and spectrum of BRCA1 and BRCA2 mutations in young Danish patients affected with bilateral or multifocal breast cancer and to determine the relationship of mutation status to family history of cancer.
  
  
  METHODS
  From the files of the Danish Breast Cancer Cooperative Group (DBCG), we selected 119 breast cancer patients diagnosed before the age of 46 years with either bilateral (n=59) or multifocal (n=61) disease.
  
  
  METHODS
  DNA from the subjects was screened for BRCA1 and BRCA2 mutations using single strand conformation analysis (SSCA) and the protein truncation test (PTT). Observed and expected cancer incidence in first degree relatives of the patients was estimated using data from the Danish Cancer Registry.
  
  
  RESULTS
  Twenty four mutation carriers were identified (20%), of whom 13 had a BRCA1 mutation and 11 carried a BRCA2 mutation. Two mutations in BRCA1 were found repeatedly in the material and accounted for seven of the 24 (29%) mutation carriers. The mutation frequency was about equal in patients with bilateral (22%) and multifocal breast cancer (18%). The incidence of breast and ovarian cancer was greatly increased in first degree relatives of BRCA1 and BRCA2 mutation carriers, but to a much lesser degree in relatives of non-carriers. An increased risk of cancer was also noted in brothers of non-carriers.
  
  
  CONCLUSIONS
  A relatively broad spectrum of germline mutations was observed in BRCA1 and BRCA2 and most of the mutations are present in other populations. Our results indicate that a diagnosis of bilateral and multifocal breast cancer is predictive of BRCA1 and BRCA2 mutation status, particularly when combined with information on the patients' age at diagnosis and family history of breast/ovarian cancer.
authors.affiliation: Department of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark. nonni@rsp.is
authors.forename: J T
authors.initials: JT
authors.lastname: Bergthorsson
authors.forename: B
authors.initials: B
authors.lastname: Ejlertsen
authors.forename: J H
authors.initials: JH
authors.lastname: Olsen
authors.forename: A
authors.initials: A
authors.lastname: Borg
authors.forename: K V
authors.initials: KV
authors.lastname: Nielsen
authors.forename: R B
authors.initials: RB
authors.lastname: Barkardottir
authors.forename: S
authors.initials: S
authors.lastname: Klausen
authors.forename: H T
authors.initials: HT
authors.lastname: Mouridsen
authors.forename: K
authors.initials: K
authors.lastname: Winther
authors.forename: K
authors.initials: K
authors.lastname: Fenger
authors.forename: A
authors.initials: A
authors.lastname: Niebuhr
authors.forename: T L
authors.initials: TL
authors.lastname: Harboe
authors.forename: E
authors.initials: E
authors.lastname: Niebuhr
mesh_terms: D000328:Adult; D017668:Age of Onset; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D003718:Denmark; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors