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Published: 2003

Total Pages: 170

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Breast cancer (BC) is a heterogeneous disease with varying clinical behavior, and response to therapy that cannot be predicted based on existing classifications. It is the primary goal of our research to identify and characterize biological pathways and individual molecular components that play a primary role in BC development and progression. In order to identify genes, gene expression profiles and molecular pathways associated with metastatic BC we performed genome-wide gene expression analysis of a large number of breast cancer samples. Both unsupervised and supervised analyses were used to identify genes differentially expressed among samples and molecular subclasses of breast cancers. We identified a unique subclass of ER-breast carcinoma and characterized the molecular phenotype. In addition formal statistical testing was used to identify genes with marked changes in expression during progression. Lymph node metastases in particular showed significant decreases in the expression of many genes corresponding to extracellular matrix proteins and proteases when compared to matched primaries. Further expression changes in a variety of genes were associated with distant metastases. Immunohistochemistry and in situ hybridization were used to validate and extend findings. A variety of in vitro and in vivo models have been used to elucidate specific molecular correlations.