© 2003 by Oxford University Press
© 2003 Oxford University Press
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Germline BRCA1 Mutations and a Basal Epithelial Phenotype in Breast Cancer
Affiliations of authors: W. D. Foulkes (Program in Cancer Genetics, Departments of Oncology and Human Genetics, and Department of Medicine), P. O. Chappuis (Department of Medicine, and Research Institute of the McGill University Health Centre), L. R. Bégin (Departments of Surgery and Pathology); J. R. Goffin (Department of Oncology); N. Wong (Department of Human Genetics, and Cancer Prevention Centre, Sir M. B. Davis-Jewish General Hospital), M. Trudel (Department of Pathology), McGill University, Montreal, Quebec, Canada; I. M. Stefansson, L. A. Akslen, Department of Pathology, The Gade Institute, Haukeland University Hospital, Bergen, Norway.
Correspondence to: William D. Foulkes, MB, PhD, Rm. L10–116, Division of Medical Genetics, Department of Medicine, McGill University Health Centre, 1650 Cedar Ave., Montreal, Quebec, Canada H3G 1A4 (e-mail: william.foulkes{at}mcgill.ca).
ABSTRACT
A basal epithelial phenotype is found in not more than 15% of all invasive breast cancers. Microarray studies have shown that this phenotype is associated with breast cancers that express neither estrogen receptor (ER) nor erbB-2 (HER2/neu) (i.e., ER/erbB-2–negative tumors). The ER/erbB-2– negative phenotype is also found in breast cancers occurring in BRCA1 mutation carriers (i.e., BRCA1-related breast cancers). We tested the hypothesis that BRCA1-related breast cancers are more likely than non–BRCA1/ 2-related breast cancer to express a basal epithelial phenotype. Among 292 breast cancer specimens previously analyzed for ER, erbB-2, p53, and germline mutations in BRCA1 and BRCA2, we identified 76 that did not overexpress ER or erbB-2. Of the 72 specimens with sufficient material for testing, 40 expressed stratified epithelial cytokeratin 5 and/or 6 (5/6). In univariate analysis, the expression of cytokeratin 5/6 was statistically significantly associated with BRCA1-related breast cancers (odds ratio = 9.0, 95% confidence interval = 1.9 to 43; P = .002, two-sided Fisher’s exact test). Thus, germline BRCA1 mutations appear to be associated with a distinctive breast cancer phenotype.
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Correspondence about this Article
- Re: Germline BRCA1 Mutations and a Basal Epithelial Phenotype in Breast Cancer
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J Natl Cancer Inst 2004 96: 712-713.[Extract] [Full Text] [PDF]
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- José Palacios, Emiliano Honrado, Ana Osorio, Orland Diez, Carmen Rivas, and Javier Benítez
J Natl Cancer Inst 2004 96: 712-714.[Extract] [Full Text] [PDF]
- RESPONSE: Re: Germline BRCA1 Mutations and a Basal Epithelial Phenotype in Breast Cancer
- William D. Foulkes and Lars A. Akslen
J Natl Cancer Inst 2004 96: 714.[Extract] [Full Text] [PDF]
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J. B. Arnes, J.-S. Brunet, I. Stefansson, L. R. Begin, N. Wong, P. O. Chappuis, L. A. Akslen, and W. D. Foulkes Placental Cadherin and the Basal Epithelial Phenotype of BRCA1-Related Breast Cancer Clin. Cancer Res., June 1, 2005; 11(11): 4003 - 4011. [Abstract] [Full Text] [PDF]
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K. Collett, I. M. Stefansson, J. Eide, A. Braaten, H. Wang, G. E. Eide, S. O. Thoresen, W. D. Foulkes, and L. A. Akslen A Basal Epithelial Phenotype Is More Frequent in Interval Breast Cancers Compared with Screen Detected Tumors Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1108 - 1112. [Abstract] [Full Text] [PDF]
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S. A. Narod and K. Offit Prevention and Management of Hereditary Breast Cancer J. Clin. Oncol., March 10, 2005; 23(8): 1656 - 1663. [Full Text] [PDF]
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S. GANESAN, A.L. RICHARDSON, Z.C. WANG, J.D. IGLEHART, A. MIRON, J. FEUNTEUN, D. SILVER, and D.M. LIVINGSTON Abnormalities of the Inactive X Chromosome Are a Common Feature of BRCA1 Mutant and Sporadic Basal-like Breast Cancer Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 93 - 97. [Abstract] [PDF]
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A.N.J. TUTT, C.J. LORD, N. MCCABE, H. FARMER, N. TURNER, N.M. MARTIN, S.P. JACKSON, G.C.M. SMITH, and A. ASHWORTH Exploiting the DNA Repair Defect in BRCA Mutant Cells in the Design of New Therapeutic Strategies for Cancer Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 139 - 148. [Abstract] [PDF]
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T. O. Nielsen, F. D. Hsu, K. Jensen, M. Cheang, G. Karaca, Z. Hu, T. Hernandez-Boussard, C. Livasy, D. Cowan, L. Dressler, et al. Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma Clin. Cancer Res., August 15, 2004; 10(16): 5367 - 5374. [Abstract] [Full Text] [PDF]
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P. van der Groep, A. Bouter, R. van der Zanden, F. H. Menko, H. Buerger, R. H.M. Verheijen, E. van der Wall, and P. J. van Diest Re: Germline BRCA1 Mutations and a Basal Epithelial Phenotype in Breast Cancer J Natl Cancer Inst, May 5, 2004; 96(9): 712 - 713. [Full Text] [PDF]
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J. Palacios, E. Honrado, A. Osorio, O. Diez, C. Rivas, and J. Benitez Re: Germline BRCA1 Mutations and a Basal Epithelial Phenotype in Breast Cancer J Natl Cancer Inst, May 5, 2004; 96(9): 712 - 714. [Full Text] [PDF]
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