title: Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype.
abstract: OBJECTIVE
  To investigate the proportion of breast cancers arising in patients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients.
  
  
  METHODS
  Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin.
  
  
  RESULTS
  All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls.
  
  
  CONCLUSIONS
  The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.
authors: The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom. s.lakhani@uq.edu.au
authors: Sunil R
authors: SR
authors: Lakhani
authors: Jorge S
authors: JS
authors: Reis-Filho
authors: Laura
authors: L
authors: Fulford
authors: Frederique
authors: F
authors: Penault-Llorca
authors: Marc
authors: M
authors: van der Vijver
authors: Suzanne
authors: S
authors: Parry
authors: Timothy
authors: T
authors: Bishop
authors: Javier
authors: J
authors: Benitez
authors: Carmen
authors: C
authors: Rivas
authors: Yves-Jean
authors: YJ
authors: Bignon
authors: Jenny
authors: J
authors: Chang-Claude
authors: Ute
authors: U
authors: Hamann
authors: Cees J
authors: CJ
authors: Cornelisse
authors: Peter
authors: P
authors: Devilee
authors: Matthias W
authors: MW
authors: Beckmann
authors: Carolin
authors: C
authors: Nestle-Krämling
authors: Peter A
authors: PA
authors: Daly
authors: Neva
authors: N
authors: Haites
authors: Jenny
authors: J
authors: Varley
authors: Fiona
authors: F
authors: Lalloo
authors: Gareth
authors: G
authors: Evans
authors: Christine
authors: C
authors: Maugard
authors: Hanne
authors: H
authors: Meijers-Heijboer
authors: Jan G M
authors: JG
authors: Klijn
authors: Edith
authors: E
authors: Olah
authors: Barry A
authors: BA
authors: Gusterson
authors: Silvana
authors: S
authors: Pilotti
authors: Paolo
authors: P
authors: Radice
authors: Siegfried
authors: S
authors: Scherneck
authors: Hagay
authors: H
authors: Sobol
authors: Jocelyne
authors: J
authors: Jacquemier
authors: Teresa
authors: T
authors: Wagner
authors: Julian
authors: J
authors: Peto
authors: Michael R
authors: MR
authors: Stratton
authors: Lesley
authors: L
authors: McGuffog
authors: Douglas F
authors: DF
authors: Easton
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis*; D018570:Risk Assessment; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D007633:Keratins