IntroductionBreast 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 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 based on 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 (hazard rate (HR) = 0.30, 95% confidence interval (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.
Conclusions:
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 in at least five distinct subgroups. The development of distant metastasis in basal-like tumors is associated with presence of central fibrosis and a small amount of lymphocytic infiltrate.