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. Jens en discovered the physiologic target, the estrogen receptor, that regulates estrogen action in its target tissues and Lerner discovered the first nons teroidal antiestrogen MER25. However, the success of tamoxifen as a treatme nt of breast cancer opened the door for the testing of the worth of tamoxif en to reduce breast cancer incidence in high-risk women. In 1998, Fisher sh owed that tamoxifen could reduce breast cancer incidence by 50%. Neverthele ss, only half the women who develop breast cancer have risk factors other t han age, so what can be done for women without risk factors? The recognitio n that nonsteroidal antiestrogens have the ability to modulate estrogen act ion selectively has advanced the design and development of new drug for mul tiple diseases. Tamoxifen and raloxifene maintain bone density and raloxife ne 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 a s selective estrogen receptor modulators (SERMs) and the challenge is to de sign new agents for multiple applications. If the 20th century was the era of chemotherapy, the 21st century will be the era of chemoprevention. (C) 2 000 Elsevier Science Ltd. All rights reserved.