title: The prevalence of BRCA1 mutations among young women with triple-negative breast cancer.
abstract: BACKGROUND
  Molecular screening for BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer. Features of hereditary breast cancer include an early age-of-onset and over-representation of the 'triple-negative' phenotype (negative for estrogen-receptor, progesterone-receptor and HER2). The decision to offer genetic testing to a breast cancer patient is usually based on her family history, but in the absence of a family history of cancer, some women may qualify for testing based on the age-of-onset and/or the pathologic features of the breast cancer.
  
  
  METHODS
  We studied 54 women who were diagnosed with high-grade, triple-negative invasive breast cancer at or before age 40. These women were selected for study because they had little or no family history of breast or ovarian cancer and they did not qualify for genetic testing using conventional family history criteria. BRCA1 screening was performed using a combination of fluorescent multiplexed-PCR analysis, BRCA1 exon-13 6 kb duplication screening, the protein truncation test (PTT) and fluorescent multiplexed denaturing gradient gel electrophoresis (DGGE). All coding exons of BRCA1 were screened. The two large exons of BRCA2 were also screened using PTT. All mutations were confirmed with direct sequencing.
  
  
  RESULTS
  Five deleterious BRCA1 mutations and one deleterious BRCA2 mutation were identified in the 54 patients with early-onset, triple-negative breast cancer (11%).
  
  
  CONCLUSIONS
  Women with early-onset triple-negative breast cancer are candidates for genetic testing for BRCA1, even in the absence of a family history of breast or ovarian cancer.
authors.affiliation: Women's College Research Institute, Department of Public Health, The University of Toronto, Toronto, Canada. sryoung37@aol.com
authors.forename: S R
authors.initials: SR
authors.lastname: Young
authors.forename: Robert T
authors.initials: RT
authors.lastname: Pilarski
authors.forename: Talia
authors.initials: T
authors.lastname: Donenberg
authors.forename: Charles
authors.initials: C
authors.lastname: Shapiro
authors.forename: Lyn S
authors.initials: LS
authors.lastname: Hammond
authors.forename: Judith
authors.initials: J
authors.lastname: Miller
authors.forename: Karen A
authors.initials: KA
authors.lastname: Brooks
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cohen
authors.forename: Beverly
authors.initials: B
authors.lastname: Tenenholz
authors.forename: Damini
authors.initials: D
authors.lastname: Desai
authors.forename: Inuk
authors.initials: I
authors.lastname: Zandvakili
authors.forename: Robert
authors.initials: R
authors.lastname: Royer
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone