Oncogenes, breast cancer, and chemoprevention

Perturbations of oncogenes in breast carcinoma include amplifications of the HER-2/neu and PRAD1 genes, as well as p53 mutations. Some of these lesions frequently appear in early cancers such as ductal carcinoma in situ and are stable as the tumors become invasive and metastasize. Thus these findings suggest that oncogene mutations may define a point of origin for a given breast cancer, and are fixed lesions during tumor progression. Such germline abnormalities may occur at the BRCA1, H-RAS VNTR, and p53 loci. The rational use of genetics may be to identify women at high risk for the development of breast cancer so that they may be enrolled in future chemoprevention trials.