title: Evaluation of BRCA1/2 mutational status among German and Austrian women with triple-negative breast cancer.
abstract: OBJECTIVE
  Testing for BRCA1 and BRCA2 mutations in breast cancer patients is used to identify the risk of second primary cancers and the risk of cancer in the patients' family. Women with triple-negative breast cancer (TNBC) are thought to be more likely to be BRCA1/2 mutation carriers, but most national guidelines for genetic testing, including those used in Germany and Austria, do not consider receptor triple negativity.
  
  
  METHODS
  We determined the prevalence of BRCA1 and BRCA2 mutations within a cohort of 100 unselected TNBC cases, including patients from Germany and Austria to identify those BRCA-positive patients with a masked family history and who would have been missed due to respective current national guidelines. Double-stranded Sanger sequencing of all exons of BRCA1 and BRCA2, respectively, was performed.
  
  
  RESULTS
  We identified a total of 13 deleterious mutations in BRCA1 and a total of four deleterious mutations in BRCA2. The total rate of deleterious BRCA1/2 mutation carriers was 21 % in our cohort. Six novel mutations, including two deleterious mutations, have been identified, which have not been described in public mutation databases so far. According to current German and Austrian national guidelines for genetic testing, 38.1 and 52.4 %, respectively, of BRCA1/2 mutation carriers would have been overlooked.
  
  
  CONCLUSIONS
  We conclude that the prevalence of BRCA1 and BRCA2 mutations is high in TNBC patients and that BRCA1/2 mutations are not restricted to young women or patients with a positive family history. Receptor triple negativity should therefore be considered in BRCA1/2 genetic testing guidelines.
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria.
authors.forename: Axel
authors.initials: A
authors.lastname: Muendlein
authors.affiliation: GATC Biotech AG, Constance, Germany.
authors.forename: Bettina H
authors.initials: BH
authors.lastname: Rohde
authors.affiliation: Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Gasser
authors.affiliation: Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
authors.forename: Anton
authors.initials: A
authors.lastname: Haid
authors.affiliation: Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Rauch
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria.
authors.forename: Elena
authors.initials: E
authors.lastname: Kinz
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Drexel
authors.affiliation: LifeCodexx AG, Constance, Germany.
authors.forename: Wera
authors.initials: W
authors.lastname: Hofmann
authors.affiliation: GATC Biotech AG, Constance, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Schindler
authors.affiliation: GATC Biotech AG, Constance, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Kapoor
authors.affiliation: Onkologie Ravensburg, Ravensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria. labor@vivit.at.|Academic Teaching Hospital Feldkirch, Feldkirch, Austria. labor@vivit.at.
authors.forename: Alois H
authors.initials: AH
authors.lastname: Lang
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria / Q000453:epidemiology; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA1; BRCA2; Genetic testing; Guidelines; Triple-negative breast cancer