Characterization of Breast Cancer Progression by Analysis of Genetic Markers.

Abstract : The earliest events in the pathogenesis of breast cancer typically involve the loss of a normal growth regulatory mechanism by a ductal or lobular epithelial cell. Progression of the disease through the stages of intraductal proliferation to invasive carcinoma and then to metastatic disease appears to require additional alterations in growth regulatory pathways. A substantial body of evidence now supports the idea that these alterations in growth regulation result from genetic events such as point mutation, deletion, and gene amplification 1-4. Our study alms to characterize genetic alterations in breast tumors at the various stages of tumor progression. If metastasis requires additional genetic events beyond those responsible for the intraductal and invasive components of the tumor, one should find genetic alterations in the metastasis that are not present in primary tumor. Alternatively, there may be certain genetic lesions which occur early in tumor development that can predispose a tumor to metastasize without the acquisition of additional genetic defects. The identification of such a lesion would provide an important prognostic indicator, because it would provide a means for predicting the likelihood of the development of metastatic disease in tumors identified at an early stage. The characterization of genetic changes present in individual tumor components thus offers the possibility of identifying new prognostic indicators as well as helping to elucidate the significance of genetic events to tumor progression.