title: Tumour morphology predicts PALB2 germline mutation status.
abstract: BACKGROUND
  Population-based studies of breast cancer have estimated that at least some PALB2 mutations are associated with high breast cancer risk. For women carrying PALB2 mutations, knowing their carrier status could be useful in directing them towards effective cancer risk management and therapeutic strategies. We sought to determine whether morphological features of breast tumours can predict PALB2 germline mutation status.
  
  
  METHODS
  Systematic pathology review was conducted on breast tumours from 28 female carriers of PALB2 mutations (non-carriers of other known high-risk mutations, recruited through various resources with varying ascertainment) and on breast tumours from a population-based sample of 828 Australian women diagnosed before the age of 60 years (which included 40 BRCA1 and 18 BRCA2 mutation carriers). Tumour morphological features of the 28 PALB2 mutation carriers were compared with those of 770 women without high-risk mutations.
  
  
  RESULTS
  Tumours arising in PALB2 mutation carriers were associated with minimal sclerosis (odds ratio (OR)=19.7; 95% confidence interval (CI)=6.0-64.6; P=5 × 10(-7)). Minimal sclerosis was also a feature that distinguished PALB2 mutation carriers from BRCA1 (P=0.05) and BRCA2 (P=0.04) mutation carriers.
  
  
  CONCLUSIONS
  This study identified minimal sclerosis to be a predictor of germline PALB2 mutation status. Morphological review can therefore facilitate the identification of women most likely to carry mutations in PALB2.
authors.affiliation: Genetic Epidemiology Laboratory, The University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: Z L
authors.initials: ZL
authors.lastname: Teo
authors.forename: E
authors.initials: E
authors.lastname: Provenzano
authors.forename: G S
authors.initials: GS
authors.lastname: Dite
authors.forename: D J
authors.initials: DJ
authors.lastname: Park
authors.forename: C
authors.initials: C
authors.lastname: Apicella
authors.forename: S D
authors.initials: SD
authors.lastname: Sawyer
authors.forename: P A
authors.initials: PA
authors.lastname: James
authors.forename: G
authors.initials: G
authors.lastname: Mitchell
authors.forename: A H
authors.initials: AH
authors.lastname: Trainer
authors.forename: G J
authors.initials: GJ
authors.lastname: Lindeman
authors.forename: K
authors.initials: K
authors.lastname: Shackleton
authors.forename: L
authors.initials: L
authors.lastname: Cicciarelli
authors.forename: S S
authors.initials: SS
authors.lastname: Buys
authors.forename: I L
authors.initials: IL
authors.lastname: Andrulis
authors.forename: A M
authors.initials: AM
authors.lastname: Mulligan
authors.forename: G
authors.initials: G
authors.lastname: Glendon
authors.forename: E M
authors.initials: EM
authors.lastname: John
authors.forename: M B
authors.initials: MB
authors.lastname: Terry
authors.forename: M
authors.initials: M
authors.lastname: Daly
authors.forename: F A
authors.initials: FA
authors.lastname: Odefrey
authors.forename: T
authors.initials: T
authors.lastname: Nguyen-Dumont
authors.forename: G G
authors.initials: GG
authors.lastname: Giles
authors.forename: J G
authors.initials: JG
authors.lastname: Dowty
authors.forename: I
authors.initials: I
authors.lastname: Winship
authors.forename: D E
authors.initials: DE
authors.lastname: Goldgar
authors.forename: J L
authors.initials: JL
authors.lastname: Hopper
authors.forename: M C
authors.initials: MC
authors.lastname: Southey
mesh_terms: D000328:Adult; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D012306:Risk; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins