The strategic use of antiestrogens to control the development and growth of breast cancer.

Tamoxifen has become the endocrine treatment of choice for all stages of breast cancer. Its low incidence of side effects and proven survival advantage observed during adjuvant therapy in postmenopausal women with node-positive disease has encouraged the use of long-term treatment for patients to benefit fully from therapy. The drug has an appropriate level of estrogen-like effects that could be beneficial to maintain bone density and prevent development of coronary heart disease by lowering circulating cholesterol. These effects might be useful in all patients with estrogen receptor-positive breast cancer who currently are receiving no therapy. This antiestrogenic agent could be effective therapy to deter recurrence, and the estrogen-like side effects support the physiologic processes of the patient as hormone-replacement therapy. In the laboratory, a tamoxifen-stimulated breast cancer model has been described in vivo. This form of drug resistance may occur in patients after long-term or indefinite adjuvant therapy. Novel pure antiestrogenic drugs have been discovered that soon will become available as second-line therapy after tamoxifen failure. In addition, tamoxifen is being evaluated in the United Kingdom as chemosuppressive therapy to prevent the development of breast cancer in high-risk women. A similar clinical evaluation is underway in the United States.