Exploring Molecular Pathways of Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a high rate of proliferation and metastasis, as well as poor prognosis for advanced-stage disease. Although TNBC was previously classified together with basal-like and BRCA1/2-related breast cancers, genomic profiling now shows that there is incomplete overlap, with important distinctions associated with each subtype. The biology of TNBC is still poorly understood; therefore, to define the relative contributions of major cellular pathways in TNBC, we have studied its molecular signature based on analysis of gene expression. Comparisons were then made with normal breast tissue. Our results suggest the existence of molecular networks in TNBC, characterized by explicit alterations in the cell cycle, DNA repair, nucleotide synthesis, metabolic pathways, NF-κB signaling, inflammatory response, and angiogenesis. Moreover, we also characterized TNBC as a cancer of mixed phenotypes, suggesting that TNBC extends beyond the basal-like molecular signature and may constitute an independent subtype of breast cancer. The data provide a new insight into the biology of TNBC.