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[Cancer Research 64, 830-835, February 1, 2004]
© 2004 American Association for Cancer Research


Advances in Brief

The Prognostic Implication of the Basal-Like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) Phenotype of BRCA1-Related Breast Cancer

William D. Foulkes1–4,7,8, Jean-Sébastien Brunet1,9, Ingunn M. Stefansson10, Oddbjørn Straume10, Pierre O. Chappuis7, Louis R. Bégin5,6, Nancy Hamel1,7, John R. Goffin2, Nora Wong3,8, Michel Trudel6, Linda Kapusta11, Peggy Porter12 and Lars A. Akslen10

1 Program in Cancer Genetics and Departments of 2 Oncology, 3 Human Genetics, 4 Medicine, 5 Surgery, and 6 Pathology, 7 Research Institute of the McGill University Health Centre, and 8 Cancer Prevention Centre, Sir M. B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada; 9 Algorithme Pharma, Montreal, Quebec, Canada; 10 Department of Pathology, The Gade Institute, Haukeland University Hospital, Bergen, Norway; 11 Department of Pathology, Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; and 12 Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center and Department of Pathology, University of Washington, Seattle, Washington

Previous studies have shown that BRCA1-related breast cancers are often high-grade tumors that do not express estrogen receptors, HER2, p27Kip1, or cyclin D1, but do express p53 and cyclin E. In addition, the expression of cytokeratin 5/6 (CK5/6), indicating a basal epithelial phenotype, is frequent in BRCA1-related breast cancer. Here, in a series of 247 breast cancers, we demonstrate that CK5/6 expression was associated with nearly all of the features of BRCA1-related breast cancer and was also associated with a poor prognosis. In a parsimonious multivariable proportional hazards model, protein levels of cyclin E, p27Kip1, p53, and the presence of glomeruloid microvascular proliferation all independently predicted outcome after breast cancer. In this model, only cyclin E and p27Kip1 levels were independent predictors in lymph node-negative cancers, whereas glomeruloid microvascular proliferation and tumor size independently predicted outcome in node-positive disease. The molecular determinants of the basal epithelial phenotype encapsulate many of the key features of breast cancers occurring in germ-line BRCA1 mutation carriers and have independent prognostic value. Basal breast cancer deserves recognition as an important subtype of breast cancer.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2004 by the American Association for Cancer Research.