Triple-negative breast cancer: Present challenges and new perspectives

Abstract 

Triple-negative breast cancers (TNBC), characterized by absence of estrogen receptor (ER), progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), are typically associated with poor prognosis, due to aggressive tumor phenotype(s), only partial response to chemotherapy and present lack of clinically established targeted therapies. Advances in the design of individualized strategies for treatment of TNBC patients require further elucidation, by combined ‘omics’ approaches, of the molecular mechanisms underlying TNBC phenotypic heterogeneity, and the still poorly understood association of TNBC with BRCA1 mutations. An overview is here presented on TNBC profiling in terms of expression signatures, within the functional genomic breast tumor classification, and ongoing efforts toward identification of new therapy targets and bioimaging markers. Due to the complexity of aberrant molecular patterns involved in expression, pathological progression and biological/clinical heterogeneity, the search for novel TNBC biomarkers and therapy targets requires collection of multi-dimensional data sets, use of robust multivariate data analysis techniques and development of innovative systems biology approaches.

Keywords: Triple-negative breast cancer, Systems biology, BRCA1, BRCA2, Chemotherapy, Targeted therapies

Abbreviations: aCGH, array comparative genomic hybridization, CK, cytokeratin, CI, confidence interval, EGF, epidermal growth factor, EGFR (or HER1), epidermal growth factor receptor, EMT, epithelial–mesenchymal transition, ER, estrogen receptor, HER2 (or Her2/neu, or ErbB2), human epidermal growth factor receptor 2, HMMR, hyaluronan-mediated mobility receptor, HR-MAS, high resolution magic angle spinning, IHC, immunohistochemistry, LC, liquid chromatography, MNI, mode-of-action by network identification, MRI, magnetic resonance imaging, MRS, magnetic resonance spectroscopy, MRSI, magnetic resonance spectroscopic imaging, ODE, ordinary differential equation, PARP, poly(ADP-ribose) polymerase, PCA, principal component analysis, PET, positron emission tomography, PR, progesterone receptor, Rb, retinoblastoma, ROC, receiver operating characteristic, TK, tyrosine kinase, TKI, tyrosine kinase inhibitor, TNBC, triple-negative breast cancer