Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer

Mod Pathol. 2007 Aug;20(8):864-70. doi: 10.1038/modpathol.3800830. Epub 2007 Jun 1.


Although breast cancer is the second most common cause of central nervous system (CNS) metastases with a notable increase of incidence, only few studies on brain-metastasizing breast cancer are available. In this immunohistochemical and fluorescence in situ hybridization (FISH) study, metastases to the CNS (n=85) and primary breast cancers, with known involvement of the CNS (n=44) including paired primary and metastasized tumours (n=23), were investigated retrospectively for the expression of oestrogen- (ER) and progesterone- (PR) hormone receptors, Her-2/neu, epidermal growth factor receptor (EGFR), Ki-67, and cytokeratins (CKs) 5/14. The majority of brain metastases were steroid hormone receptor negative (ER 66%, PR 82%) corresponding to the findings in primary tumours with known involvement of the CNS (68% ER-negative, 75% PR-negative). The frequency of HER-2/neu-overexpressing or -amplified cancers was increased in both groups (34 and 32%, respectively). EGFR expression was more frequent in metastases (41%) than in primary tumours (16%). The proportions of cases with a basal phenotype were 26 and 30%, respectively. In paired primary tumours and metastases to the CNS, constancy of Her-2/neu status was observed in 87% of cases with only one sample turning Her-2/neu-negative and two samples acquiring overexpression/amplification in brain metastases. In contrast, steroid hormone receptors exhibited more frequently a loss of expression (17%) than a gain (9%) with 74% revealing a constant phenotype. We conclude that brain-metastasizing breast cancer belongs predominantly to the basal type or Her-2/neu type. Primary and metastatic tumours differ from each other only in a minority of cases, leading rather to a loss of steroid hormone receptors and to a gain of EGFR and Her-2/neu.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / chemistry*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • ErbB Receptors / analysis
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry / methods
  • In Situ Hybridization, Fluorescence
  • Keratin-14 / analysis
  • Keratin-5 / analysis
  • Ki-67 Antigen / analysis
  • Neoplasms, Basal Cell / chemistry*
  • Neoplasms, Basal Cell / genetics
  • Neoplasms, Basal Cell / secondary
  • Receptor, ErbB-2 / analysis*
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Retrospective Studies
  • Tissue Array Analysis


  • KRT14 protein, human
  • KRT5 protein, human
  • Keratin-14
  • Keratin-5
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2