Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas

Breast Cancer Res. 2007;9(5):R65. doi: 10.1186/bcr1771.


Introduction: Breast cancer is a heterogeneous group of tumors, and can be subdivided on the basis of histopathological features, genetic alterations and gene-expression profiles. One well-defined subtype of breast cancer is characterized by a lack of HER2 gene amplification and estrogen and progesterone receptor expression ('triple-negative tumors'). We examined the histopathological and gene-expression profile of triple-negative tumors to define subgroups with specific characteristics, including risk of developing distant metastases.

Methods: 97 triple-negative tumors were selected from the fresh-frozen tissue bank of the Netherlands Cancer Institute, and gene-expression profiles were generated using 35K oligonucleotide microarrays. In addition, histopathological and immunohistochemical characterization was performed, and the findings were associated to clinical features.

Results: All triple-negative tumors were classified as basal-like tumors on the basis of their overall gene-expression profile. Hierarchical cluster analysis revealed five distinct subgroups of triple-negative breast cancers. Multivariable analysis showed that a large amount of lymphocytic infiltrate (HR = 0.30, 95% CI 0.09-0.96) and absence of central fibrosis in the tumors (HR = 0.14, 95% CI 0.03-0.62) were associated with distant metastasis-free survival.

Conclusion: Triple-negative tumors are synonymous with basal-like tumors, and can be identified by immunohistochemistry. Based on gene-expression profiling, basal-like tumors are still heterogeneous and can be subdivided into at least five distinct subgroups. The development of distant metastasis in basal-like tumors is associated with the presence of central fibrosis and a small amount of lymphocytic infiltrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carcinoma, Adenoid Cystic / genetics
  • Carcinoma, Adenoid Cystic / metabolism
  • Carcinoma, Adenoid Cystic / pathology
  • Carcinoma, Intraductal, Noninfiltrating / genetics
  • Carcinoma, Intraductal, Noninfiltrating / metabolism
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / pathology
  • ErbB Receptors / metabolism
  • Gene Amplification
  • Gene Expression Profiling*
  • Genes, erbB-2
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism


  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ErbB Receptors