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

Sunil R. Lakhani, Jorge S. Reis-Filho, Laura Fulford, Frederique Renault-Llorca, Marc Der Van Vijver, Suzanne Parry, Timothy Bishop, Javier Benitez, Carmen Rivas, Yves Jean Bignon, Jenny Chang-Claude, Ute Hamann, Cees J. Cornelisse, Peter Devilee, Matthias W. Beckmann, Carolin Nestle-Krämling, Peter A. Daly, Neva Haites, Jenny Varley, Fiona LallooGareth Evans, Christine Maugard, Hanne Meijers-Heijboer, Jan G.M. Klijn, Edith Olah, Barry A. Gusterson, Silvana Pilotti, Paolo Radice, Siegfried Scherneck, Hagay Sobol, Jocelyne Jacquemier, Teresa Wagner, Julian Peto, Michael R. Stratton, Lesley McGuffog, Douglas F. Easton

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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.

Original languageEnglish
Pages (from-to)5175-5180
Number of pages6
JournalClinical Cancer Research
Volume11
Issue number14
DOIs
Publication statusPublished - Jul 15 2005

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lakhani, S. R., Reis-Filho, J. S., Fulford, L., Renault-Llorca, F., Van Vijver, M. D., Parry, S., Bishop, T., Benitez, J., Rivas, C., Bignon, Y. J., Chang-Claude, J., Hamann, U., Cornelisse, C. J., Devilee, P., Beckmann, M. W., Nestle-Krämling, C., Daly, P. A., Haites, N., Varley, J., ... Easton, D. F. (2005). Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clinical Cancer Research, 11(14), 5175-5180. https://doi.org/10.1158/1078-0432.CCR-04-2424