Exploring molecular pathways of triple-negative breast cancer - PubMed (original) (raw)

Exploring molecular pathways of triple-negative breast cancer

Valeria Ossovskaya et al. Genes Cancer. 2011 Sep.

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.

Keywords: DNA repair; NF-κB; cell cycle; molecular pathways; triple-negative breast cancer (TNBC); tumor metabolism.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Valeria Ossovskaya is an employee of BiPar Sciences, Inc. (subsidiary of Sanofi). Yipeng Wang, Adam Budoff, Gordon Vansant, and Joseph Monforte are employees of AltheaDx, Inc. Qiang Xu is a former employee of AltheaDx, Inc. Alexander Lituev and Olga Potapova are employees of Cureline, Inc. Nikolai Daraselia is an employee of Ariadne, Inc.

Figures

Figure 1.

Figure 1.

Gene expression changes in the NF-κB pathway in triple-negative breast cancer. ECM = extracellular matrix.

Figure 2.

Figure 2.

Gene expression changes in DNA repair pathways in triple-negative breast cancer.

Figure 3.

Figure 3.

Gene expression changes in PARP1 pathways in triple-negative breast cancer.

Figure 4.

Figure 4.

Gene expression changes in cell cycle pathways in triple-negative breast cancer.

Figure 5.

Figure 5.

Gene expression changes in apoptotic pathways in triple-negative breast cancer.

Figure 6.

Figure 6.

Heat map depicting patterns of triple-negative breast cancer samples in gene expression selected by the relationship with intrinsic subtypes of breast cancer, such as luminal A, luminal B, HER2-enriched, basal-like, and a normal breast-like group–, (for details of the analysis, see Materials and Methods).

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References

    1. Cleere DW. Triple-negative breast cancer: a clinical update. Community Oncol. 2010;7:203–11
    1. Coughlin SS, Ekwueme DU. Breast cancer as a global health concern. Cancer Epidemiol. 2009;33:315–8 - PubMed
    1. Ismail-Khan R, Bui MM. A review of triple-negative breast cancer. Cancer Control. 2010;17:173–6 - PubMed
    1. Carey LA. Directed therapy of subtypes of triple-negative breast cancer. Oncologist. 2010;15(Suppl 5):49–56 - PubMed
    1. Perou CM. Molecular stratification of triple-negative breast cancers. Oncologist. 2010;15(Suppl 5):39–48 - PubMed

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