title: Validation of the pedigree assessment tool (PAT) in families with BRCA1 and BRCA2 mutations.
abstract: BACKGROUND
  The lifetime risk of breast cancer (BC) in patients with hereditary breast cancer syndromes is as high as 80%. The Pedigree Assessment Tool (PAT) is a scoring system to aid in identifying these patients. This validation study compares the PAT to BRCA gene mutation probability models in predicting suitability for genetic referral.
  
  
  METHODS
  Retrospective review identified subjects undergoing genetic counseling and BRCA testing from 2001 to 2008 at two institutions. PAT score and BRCA mutation probabilities were calculated using Myriad II and Penn II models. Comparisons were made between models in ability to discriminate patients appropriate for genetic evaluation based on accuracy in predicting a positive test result.
  
  
  RESULTS
  Records evaluated represent 520 families. BRCA testing revealed 146 mutation-positive and 374 mutation-negative families. c-Statistic analysis was used to compare the discriminating ability of the models to correctly assign families as mutation (+) and (-). Both the PAT and Penn II model outperformed the Myriad II model. Using a threshold PAT score >or=8 and mutation probability >or=10% to assign families as mutation (+) versus (-), sensitivity, specificity, and positive and negative predictive values were calculated for each model. The PAT was more sensitive than the Myriad II model and more specific than the Penn II model.
  
  
  CONCLUSIONS
  In overall performance, the PAT is at least comparable to the Myriad II and Penn II models in screening women appropriate for genetic referral. Simplicity and identification of families with non-BRCA hereditary BC syndromes suggest that the PAT is better suited for BC risk screening.
authors.affiliation: Surgical Oncology, Emory University, Atlanta, GA, USA. teller@musc.edu
authors.forename: P
authors.initials: P
authors.lastname: Teller
authors.forename: K F
authors.initials: KF
authors.lastname: Hoskins
authors.forename: A
authors.initials: A
authors.lastname: Zwaagstra
authors.forename: C
authors.initials: C
authors.lastname: Stanislaw
authors.forename: R
authors.initials: R
authors.lastname: Iyengar
authors.forename: V L
authors.initials: VL
authors.lastname: Green
authors.forename: S G A
authors.initials: SG
authors.lastname: Gabram
mesh_terms: D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005188:False Negative Reactions; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity
chemical_list: D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human