The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer

Cancer Res. 2004 Feb 1;64(3):830-5. doi: 10.1158/0008-5472.can-03-2970.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • 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
  • Middle Aged
  • Mutation
  • Prognosis
  • Proportional Hazards Models
  • Survival Rate
  • Tumor Suppressor Protein p53 / biosynthesis*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics

Substances

  • Cell Cycle Proteins
  • Cyclin E
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Keratins