The prognostic implication of the basal-like (cyclin Ehigh/p27low/p53+/ glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer

Previous studies have shown that BRCA1-related breast cancers are often high-grade tumors that do not express estrogen receptors, HER2, p27(Kip1), 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 freque...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2004-02, Vol.64 (3), p.830-835
Main Authors: FOULKES, William D, BRUNET, Jean-Sébastien, KAPUSTA, Linda, PORTER, Peggy, AKSLEN, Lars A, STEFANSSON, Ingunn M, STRAUME, Oddbjørn, CHAPPUIS, Pierre O, BEGIN, Louis R, HAMEL, Nancy, GOFFIN, John R, WONG, Nora, TRUDEL, Michel
Format: Article
Language:English
Subjects:
Adult
Aged
Antineoplastic agents
Biological and medical sciences
Breast Neoplasms - blood supply
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Cycle Proteins - biosynthesis
Cell Cycle Proteins - genetics
Cyclin E - biosynthesis
Cyclin E - genetics
Cyclin-Dependent Kinase Inhibitor p27
Female
Genes, BRCA1
Humans
Keratins - biosynthesis
Keratins - genetics
Medical sciences
Middle Aged
Mutation
Pharmacology. Drug treatments
Prognosis
Proportional Hazards Models
Survival Rate
Tumor Suppressor Protein p53 - biosynthesis
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Proteins - biosynthesis
Tumor Suppressor Proteins - genetics
Tumors
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Summary:Previous studies have shown that BRCA1-related breast cancers are often high-grade tumors that do not express estrogen receptors, HER2, p27(Kip1), 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, p27(Kip1), p53, and the presence of glomeruloid microvascular proliferation all independently predicted outcome after breast cancer. In this model, only cyclin E and p27(Kip1) 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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-03-2970