title: Selecting for BRCA1 testing using a combination of homogeneous selection criteria and immunohistochemical characteristics of breast cancers.
abstract: BACKGROUND
  BRCA1 gene-related tumours are more frequently estrogen receptor (ER) and progesterone receptor (PR) negative with a lower prevalence of human epidermal growth factor receptor 2 (HER2) overexpression or amplification. We evaluated the effectiveness of a combination of homogeneously selected criteria and immunohistochemical (IHC) characteristics of Familial Breast Cancers (FBCs) in detecting BRCA1 mutation carriers.
  
  
  METHODS
  Primary breast tumours from 93 FBC patients defined by specific eligibility criteria, based on personal and familial tumour history, were evaluated by Allred's method. The BRCA1 molecular analysis, including Multiplex Ligation-dependent Probe Amplification (MLPA), was considered as the gold standard assay.
  
  
  RESULTS
  A total of 10 BRCA1 pathogenetic mutations was found. With the exclusion of the tumours characterized by double positive receptorial status and/or strong HER2 positivity (3+), we identified 22 patients, 10 of whom resulted as BRCA1 mutation carriers. The sensitivity, specificity, positive and negative predictive values were 100%, 83.3%, 45.4% and 100% respectively.
  
  
  CONCLUSIONS
  Our findings suggest that the IHC analysis by Allred's method improves our ability to select patients for BRCA1 testing.
authors.affiliation: Department of Molecular Oncology and Translational Research, Division of Experimental Oncology 1, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy. gmiolo@libero.it
authors.forename: GianMaria
authors.initials: G
authors.lastname: Miolo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Canzonieri
authors.forename: Clelia
authors.initials: C
authors.lastname: De Giacomi
authors.forename: Lara Della
authors.initials: LD
authors.lastname: Puppa
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dolcetti
authors.forename: Davide
authors.initials: D
authors.lastname: Lombardi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Perin
authors.forename: Simona
authors.initials: S
authors.lastname: Scalone
authors.forename: Andrea
authors.initials: A
authors.lastname: Veronesi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viel
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human