TAMOXIFENS ROLE IN CHEMOPREVENTION OF BREAST-CANCER - AN UPDATE

Tamoxifen is an oral antiestrogen first used in metastatic breast canc er in the early 1970s. Large clinical trials were initiated in the lat e 1970s and early 1980s to test the drug's role as adjuvant therapy in early stage breast cancer. Observations of marked decreases in the de velopment of contralateral breast cancer among tamoxifen recipients su ggested potential for the drug in chemoprevention of breast cancer, an d a large clinical trial to test the efficacy of tamoxifen in preventi on of invasive breast cancer among women at increased risk was impleme nted in the United States in 1992. This paper reviews the rational for the clinical studies of tamoxifen as a chemopreventive agent for brea st cancer and summarizes new information that has contributed to our u nderstanding of tamoxifen's actions at the molecular and clinical leve ls. Current knowledge about the drug's mechanism of estrogenic and ant iestrogenic action and its beneficial effects on blood Lipids and bone metabolism will be presented. Recent research findings about DNA addu ct formation and hepatic lesions, tamoxifen-associated gynecologic con ditions, and the occurrence of second primary cancers in other organ s ystems will also be discussed. (C) 1995 Wiley-Liss, Inc.