Research article
Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas
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* Corresponding author: Marc J van de Vijver m.vd.vijver@nki.nl
1 Division of Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
2 Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
3 Division of Diagnostic Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Breast Cancer Research 2007, 9:R65 doi:10.1186/bcr1771
See related letters by Rakha et al., http://breast-cancer-research.com/content/9/6/404 and Kreike et al., http://breast-cancer-research.com/content/9/6/405
Published: 2 October 2007Abstract
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.