title: Prevalence of BRCA mutations in an unselected population of triple-negative breast cancer.
abstract: BACKGROUND
  This study assessed BRCA1 and BRCA2 mutation prevalence in an unselected cohort of patients with triple-negative breast cancer (BC).
  
  
  METHODS
  One hundred ninety-nine patients were enrolled. Triple negativity was defined as <1% estrogen and progesterone staining by immunohistochemistry and HER-2/neu not overexpressed by fluorescence in situ hybridization. Having given consent, patients had BRCA1 and BRCA2 full sequencing and large rearrangement analysis. Mutation prevalence was assessed among the triple-negative BC patients and the subset of patients without a family history of breast/ovarian cancer. Independent pathological review was completed on 50 patients.
  
  
  RESULTS
  Twenty-one deleterious BRCA mutations were identified--13 in BRCA1 and 8 in BRCA2 (prevalence, 10.6%). In 153 patients (76.9%) without significant family history (first-degree or second-degree relatives with BC aged <50 years or ovarian cancer at any age), 8 (5.2%) mutations were found. By using prior National Comprehensive Cancer Network (NCCN) guidelines recommending testing for triple-negative BC patients aged <45 years, 4 of 21 mutations (19%) would have been missed. Two of 21 mutations (10%) would have been missed using updated NCCN guidelines recommending testing for triple-negative BC patients aged <60 years.
  
  
  CONCLUSIONS
  The observed mutation rate was significantly higher (P = .0005) than expected based on previously established prevalence tables among patients unselected for pathology. BRCA1 mutation prevalence was lower, and BRCA2 mutation prevalence was higher, than previously described. Additional mutation carriers would have met new NCCN testing guidelines, underscoring the value of the updated criteria. Study data suggest that by increasing the age limit to 65 years, all carriers would have been identified.
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah 84020, USA. anhartma@myriad.com
authors.forename: Anne-Renee
authors.initials: AR
authors.lastname: Hartman
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Kaldate
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sailer
authors.forename: Lisa
authors.initials: L
authors.lastname: Painter
authors.forename: Charles E
authors.initials: CE
authors.lastname: Grier
authors.forename: Robbin R
authors.initials: RR
authors.lastname: Endsley
authors.forename: Marlena
authors.initials: M
authors.lastname: Griffin
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Hamilton
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Frye
authors.forename: Mark A
authors.initials: MA
authors.lastname: Silberman
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wenstrup
authors.forename: John F
authors.initials: JF
authors.lastname: Sandbach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D059645:Mutation Rate; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics