Studies on biomarker development in breast cancer

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Copyright: Millar, Ewan
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Abstract
Aim: To identify new prognostic and predictive biomarkers for clinical breast cancer, thereby improving patient selection for currently available therapies. Methods: Data derived from gene expression profiling of human breast cancer or human breast cancer cell lines, were interrogated to identify putative biomarkers in ER positive and ER negative disease. These findings were validated using immunohistochemistry on tissue microarrays constructed from the development of two independent clinical breast cancer cohorts (n=292 and n=498). Results: Prognosis in ER+ disease can be predicted by expression of BAG-1, PUMA, c-Myc and an improved biomarker signature for Luminal A and B cancer which includes Ki67 and p53. Studies identifying abnormalities in signalling pathways (PI3-kinase, Hedgehog, STARD10), HIF-1α (CAIX, FOXP3/CXCR4, SIAH2), proliferation (cyclin D1b) and DNA repair pathways (Rad21) have also identified potential biomarkers and therapeutic targets for ER negative and basal-like breast cancer. Conclusions: New biomarkers for clinical breast cancer have been identified which have the potential to improve patient selection and therapeutic decision making. Validation studies are underway in independent international randomised clinical trials to confirm these findings. The use of immunohistochemistry allows the potential rapid translation of these findings into routine Hospital Pathology clinical practice.
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Author(s)
Millar, Ewan
Supervisor(s)
Sutherland, Robert
Hawkins, Nick
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Publication Year
2011
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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