Nayfield S G
Community Oncology and Rehabilitation Branch, Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892, USA.
J Cell Biochem Suppl. 1995;22:42-50. doi: 10.1002/jcb.240590807.
Tamoxifen is an oral antiestrogen first used in metastatic breast cancer in the early 1970s. Large clinical trials were initiated in the late 1970s and early 1980s to test the drug's role as adjuvant therapy in early stage breast cancer. Observations of marked decreases in the development of contralateral breast cancer among tamoxifen recipients suggested potential for the drug in chemoprevention of breast cancer, and a large clinical trial to test the efficacy of tamoxifen in prevention of invasive breast cancer among women at increased risk was implemented in the United States in 1992. This paper reviews the rational for the clinical studies of tamoxifen as a chemopreventive agent for breast cancer and summarizes new information that has contributed to our understanding of tamoxifen's actions at the molecular and clinical levels. Current knowledge about the drug's mechanism of estrogenic and antiestrogenic action and its beneficial effects on blood lipids and bone metabolism will be presented. Recent research findings about DNA adduct formation and hepatic lesions, tamoxifen-associated gynecologic conditions, and the occurrence of second primary cancers in other organ systems will also be discussed.
他莫昔芬是一种口服抗雌激素药物，于20世纪70年代初首次用于转移性乳腺癌的治疗。20世纪70年代末和80年代初开展了大型临床试验，以测试该药物在早期乳腺癌辅助治疗中的作用。对接受他莫昔芬治疗的患者中对侧乳腺癌发病率显著降低的观察结果表明，该药物在乳腺癌化学预防方面具有潜力，1992年在美国实施了一项大型临床试验，以测试他莫昔芬对高危女性预防浸润性乳腺癌的疗效。本文回顾了他莫昔芬作为乳腺癌化学预防剂临床研究的理论依据，并总结了有助于我们在分子和临床水平上理解他莫昔芬作用的新信息。将介绍有关该药物雌激素和抗雌激素作用机制及其对血脂和骨代谢有益影响的现有知识。还将讨论有关DNA加合物形成和肝脏病变、他莫昔芬相关妇科疾病以及其他器官系统中第二原发性癌症发生情况的最新研究发现。
