Chemoprevention with antiestrogens: the beginning of the end for breast cancer. Daniel G. Miller Lecture.
In the 1960s, compounds known as nonsteroidal antiestrogens were identified as potential contraceptives, but the drugs caused the induction of ovulation in subfertile women. Tamoxifen and clomiphene were marketed for this indication. However, tamoxifen was advanced for the treatment of breast cancer in the 1970s through a close cooperation between the laboratory and the clinical trials community. The extensive use of long-term adjuvant tamoxifen has resulted in saving the lives of 400,000 women with breast cancer. Tamoxifen is a selective estrogen receptor modulator (SERM) that produces antiestrogenic actions in the breast but estrogen-like actions in bone and lowers serum cholesterol. These properties not only allowed the application of tamoxifen as the first chemopreventive in high-risk pre- and postmenopausal women but also the development of raloxifene to prevent osteoporosis with the potential to prevent breast cancer in postmenopausal women. The future development of SERMs holds the promise of preventing osteoporosis and coronary heart disease as well as breast and endometrial cancer.
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Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611, USA. vcjordan@northwestern.edu
D019943:Amino Acid Substitution; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D015195:Drug Design; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D047628:Estrogen Receptor alpha; D004967:Estrogens; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000517:prevention & control; D051379:Mice; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000517:prevention & control; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use; D051381:Rats; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016588:Anticarcinogenic Agents; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D004967:Estrogens; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride