الفهرس 
List of TablesOnly 14 pages are availabe for public view
 |  | from | 141 |  |  |
| | | from | 141 | | |
Abstract
Breast cancer is the most common malignant tumor among females around the world. The Triple-Negative Breast Cancer (TNBC) group often shows a more aggressive course than other molecular subtypes.
Not all patients with TNBC will respond equally to therapy. Choice of therapy would ideally be guided by identification of drug targets and/or surrogate predictive biomarkers. Such an approach would impart a degree of pre-treatment certainty of benefit. Factors impacting on efficacy will reflect underlying biological diversity, particularly which pathways and pathway cross talk are dominant for tumour survival and proliferation (239).
TNBC is marked by a high rates of dysfunctional DNA repair, BRCA mutation or dysfunction, p53 mutation, aberrant apoptosis, dysregulated angiogenesis, variable expression of immune response genes and high proliferation. Such features may evolve as predictive of specific treatment benefit. Other hypotheses for potential predictive tools, not restricted to TNBC, include overexpression of the anthracycline drug target, topoisomerase II alpha protein, in predicting anthracycline benefit, or analysis of the p53 pathway in predicting p53-independent taxane activity (240).
1. DNA damage
Dysfunctional DNA repair in TNBC, reflected in high genomic instability, may render TNBC particular sensitivity to DNA damaging therapy. Tools to assess tumour capacity for DNA repair may aid choice of therapy. Evaluation of baseline DNA damage may identify patients most likely to benefit from DNA targeted therapy, such as anthracyclines, platinums and PARP inhibitors, whilst treatment associated DNA damage may reflect efficacy. The Comet assay, an example of such a tool, uses single-cell gel electrophoresis to assess DNA breaks and break frequency by the appearance and intensity of a comet (Error! Reference source not f ound.) . The Comet assay may be combined with fluorescence in situ hybridisation, using labelled probes to particular DNA sequences for analysis at an even finer level of resolution (241).