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Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype

Item Type:Article
Title:Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype
Creators Name:Lakhani, S.R. and Reis-Filho, J.S. and Fulford, L. and Penault-Llorca, F. and van der Vjiver, M. and Parry, S. and Bishop, T. and Benitez, J. and Rivas, C. and Bignon, Y.J. and Chang-Claude, J. and Hamann, U. and Cornelisse, C.J. and Devilee, P. and Beckmann, M.W. and Nestle-Kramling, C. and Daly, P.A. and Haites, N. and Varley, J. and Lalloo, F. and Evans, G. and Maugard, C. and Meijers-Heijboer, H. and Klijn, J.G.M. and Olah, E. and Gusterson, B.A. and Pilotti, S. and Radice, P. and Scherneck, S. and Sobol, H. and Jacquemier, J. and Wagner, T. and Peto, J. and Stratton, M.R. and McGuffog, L. and Easton, D.F.
Abstract:Purpose: 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. Experimental Design: 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. Conclusion: 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.
Keywords:Biological Tumor Markers, Breast Neoplasms, BRCA1 Genes, BRCA2 Genes, Case-Control Studies, DNA Mutational Analysis, Estrogen Receptors, Germ-Line Mutation, Immunohistochemistry, Keratins, Multivariate Analysis, Phenotype, Prognosis, Risk Assessment, Sensitivity and Specificity
Source:Clinical Cancer Research
Publisher:American Association for Cancer Research
Page Range:5175-5180
Date:15 July 2005
Official Publication:https://doi.org/10.1158/1078-0432.CCR-04-2424
PubMed:View item in PubMed

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