( Michael S. Singer M.D. Ph.D. Harva...)Breast Cancer and HER-2/neu: Diagnostic Tools for Targeted Therapy,Health

With over 200,000 new cases and 40,000 deaths per year, breast cancer undoubtedly qualifies as one of Americas most serious health problems. Recently, efforts to develop early detection methods and more effective therapy have made important progress. This is particularly true at the molecular level, where discoveries on protein expression have translated into new diagnostic tests and targeted therapies. An example is the finding that tumors expressing estrogen receptors (so called ER+ tumors) tend to respond to tamoxifen, a selective estrogen receptor modulator. Conversely, ER tumors tend to respond better to chemotherapy and not to tamoxifen. Another revolutionary example is that of Her-2/neu protein (also called c-erbB2), which is overexpressed in approximately 2530% of breast cancers. With herceptin (trastuzumab) and other preferential medications available to treat these patients, the need has emerged for routine laboratory methods to detect Her-2/neu overexpression. A wide array of tools has arrived to fulfill this purpose.

Human cells normally carry and express two copies of Her-2/neu, which is located on chromosome 17 and encodes a cell-surface receptor for epidermal growth factor. Like many growth factor receptors, Her-2/neu functions as a tyrosine kinase and moves cells forward on the cell cycle, which involves DNA replication and cell division. Her-2/neu therefore falls into the class of proto-oncogenes. A key discovery is that some 2530% of breast cancers carry amplifications (multiple copies) of the Her-2/neu gene, which lead to overexpression of Her-2/neu protein. The over-abundance of Her-2/neu receptor accelerates the cell cycle and causes cells to divide more rapidly and haphazardly. This explain why Her-2/neu overexpression is associated with more rapid tumor growth and a worse prognosis.

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