Progress in the prevention of breast cancer: concept to reality.

In 1936, Professor Antoine Lacassagne suggested that breast cancer could be prevented by developing drugs to block estrogen action in the breast. Jensen discovered the physiologic target, the estrogen receptor, that regulates estrogen action in its target tissues and Lerner discovered the first nonsteroidal antiestrogen MER25. However, the success of tamoxifen as a treatment of breast cancer opened the door for the testing of the worth of tamoxifen to reduce breast cancer incidence in high-risk women. In 1998, Fisher showed that tamoxifen could reduce breast cancer incidence by 50%. Nevertheless, only half the women who develop breast cancer have risk factors other than age, so what can be done for women without risk factors? The recognition that nonsteroidal antiestrogens have the ability to modulate estrogen action selectively has advanced the design and development of new drug for multiple diseases. Tamoxifen and raloxifene maintain bone density and raloxifene is now used to prevent osteoporosis and is being tested as a preventive for coronary heart disease and breast cancer. The drug group is now known as selective estrogen receptor modulators (SERMs) and the challenge is to design new agents for multiple applications. If the 20th century was the era of chemotherapy, the 21st century will be the era of chemoprevention.