Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

摘要

Cancer is a highly heterogeneous disease, both morphologically and genetically. A current shortcoming in cancer prognosis and treatment is a lack of methods that adequately address the complexity and diversity of the disease. Genome wide studies can provide molecular characterization or fingerprints of cancer phenotypes linked to clinical information. The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b: refine stage-specific disease phenotypes by integration of molecular profiles with known risk factors of breast cancer such as reproductive characteristics, medical history, and histologic parameters of breast carcinomas. We will examine 100 cases in each disease stage category of 0, 1, 2, 3, 4 and unknown to evaluate 120 breast cancer associated gene markers distributed throughout the human genome. Molecular fingerprints identified from genome wide studies should delineate patterns of genomic imbalances at the level of stage -specific gene loci, providing a novel index to estimate the extent of genomic abnormality with disease progression. This knowledge should allow the integration of stage- specific therapeutic targets as treatment intervention strategies in the management of breast cancer.