title: Histopathological features of 'BRCAX' familial breast cancers in the kConFab resource.
abstract: OBJECTIVE
  In recent years histopathology has made an important contribution to the study of familial breast cancer, largely on the basis of the distinctive cancer phenotype commonly identified in BRCA1-mutation carriers. The aim of this study was to identify this phenotype amongst index cases from families in the kConFab familial breast cancer resource with no known pathogenic mutation ('BRCAX' families).
  
  
  METHODS
  The histopathology of breast cancer from 180 individuals was reviewed: 132 members of individual BRCAX families, 26 BRCA1 and 15 BRCA2 mutation carriers and seven mutation negative individuals from families with a known pathogenic mutation.
  
  
  RESULTS
  BRCAX breast cancers were a heterogeneous group with 25.8% grade 1, 37.9% grade 2 and 36.4% grade 3. Overall, 45/180 (25%) cases were designated 'BRCA1-phenotype' including 22/132 (16.7%) BRCAX cases, 18/26 (69.2%) BRCA1 and 5/15 (33.3%) BRCA2 mutation carriers. For BRCAX cases, a BRCA1 phenotype designation was negatively correlated with age.
  
  
  CONCLUSIONS
  Characteristic breast cancer pathology is not diagnostic of a germline BRCA1 mutation, but it does indicate a pathogenic mechanism that occurs with increased frequency in BRCA1 mutation carriers. In BRCAX families, BRCA1 tumour phenotype may signal the presence of an unidentified BRCA1 mutation. However, this finding must be interpreted with regard to limits of the association between histopathology and genotype, and the importance of clinical context.
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Victoria.
authors.forename: Maurice
authors.initials: M
authors.lastname: Loughrey
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Provan
authors.forename: Karen
authors.initials: K
authors.lastname: Byth
authors.forename: Rosemary L
authors.initials: RL
authors.lastname: Balleine
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics