title: Performance of BOADICEA and BRCAPRO genetic models and of empirical criteria based on cancer family history for predicting BRCA mutation carrier probabilities: a retrospective study in a sample of Italian cancer genetics clinics.
abstract: OBJECTIVE
  To evaluate in current practice the performance of BOADICEA and BRCAPRO risk models and empirical criteria based on cancer family history for the selection of individuals for BRCA genetic testing.
  
  
  METHODS
  The probability of BRCA mutation according to the three tools was retrospectively estimated in 918 index cases consecutively undergone BRCA testing at 15 Italian cancer genetics clinics between 2006 and 2008.
  
  
  RESULTS
  179 of 918 cases (19.5%) carried BRCA mutations. With the strict use of the criteria based on cancer family history 173 BRCA (21.9%) mutations would have been detected in 789 individuals. At the commonly used 10% threshold of BRCA mutation carrier probability, the genetic models showed a similar performance [PPV (38% and 37%), sensitivity (76% and 77%) and specificity (70% and 69%)]. Their strict use would have avoided around 60% of the tests but would have missed approximately 1 every 4 carriers.
  
  
  CONCLUSIONS
  Our data highlight the complexity of BRCA testing referral in routine practice and question the strict use of genetic models for BRCA risk assessment.
authors.affiliation: Unit of Hereditary Cancer, IRCCS AOU San Martino - IST, Largo Rosanna Benzi, 10, 16132 Genoa, Italy. Electronic address: liliana.varesco@hsanmartino.it.
authors.forename: L
authors.initials: L
authors.lastname: Varesco
authors.forename: V
authors.initials: V
authors.lastname: Viassolo
authors.forename: A
authors.initials: A
authors.lastname: Viel
authors.forename: V
authors.initials: V
authors.lastname: Gismondi
authors.forename: P
authors.initials: P
authors.lastname: Radice
authors.forename: M
authors.initials: M
authors.lastname: Montagna
authors.forename: E
authors.initials: E
authors.lastname: Alducci
authors.forename: L
authors.initials: L
authors.lastname: Della Puppa
authors.forename: C
authors.initials: C
authors.lastname: Oliani
authors.forename: S
authors.initials: S
authors.lastname: Tommasi
authors.forename: M A
authors.initials: MA
authors.lastname: Caligo
authors.forename: C
authors.initials: C
authors.lastname: Vivanet
authors.forename: M
authors.initials: M
authors.lastname: Zuradelli
authors.forename: P
authors.initials: P
authors.lastname: Mandich
authors.forename: M G
authors.initials: MG
authors.lastname: Tibiletti
authors.forename: P
authors.initials: P
authors.lastname: Cavalli
authors.forename: E
authors.initials: E
authors.lastname: Lucci Cordisco
authors.forename: D
authors.initials: D
authors.lastname: Turchetti
authors.forename: D
authors.initials: D
authors.lastname: Boggiani
authors.forename: R
authors.initials: R
authors.lastname: Bracci
authors.forename: P
authors.initials: P
authors.lastname: Bruzzi
authors.forename: L
authors.initials: L
authors.lastname: Bonelli
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D018579:Patient Selection; D011237:Predictive Value of Tests; D011336:Probability; D018570:Risk Assessment
keywords: BRCA mutation; Breast cancer; Genetic models; Genetic testing clinical criteria; Risk assessment