Cuzick J
Imperial Cancer Research Fund, 61 Lincoln's Inn Fields, London, UK.
IARC Sci Publ. 1996(139):99-114.
Many of the most common cancers occur in sites that are under hormonal regulation by the steroid sex hormones. These include the breast, ovary, endometrium and possibly the colon for women, and the prostate and testes for men. Much information on chemoprevention of these cancers has accrued indirectly as a result of the use of estrogens and progestagens for contraception or postmenopausal hormone replacement therapy. Estrogen-based contraceptives clearly reduce the risk of ovarian cancer, but without an opposing progestagen they increase the risk of endometrial cancer. Progestagens reduce the risk of endometrial cancer and when used premenopausally appear to be able to more than counteract the carcinogenic effect of exogenous estrogens at this site. The effect of oral contraceptives on breast cancer appears to be quite minimal, but probably increases risk when taken for long periods at a young age. Recent studies suggest that the use of an agonist of leuteinizing hormone releasing hormone as a contraceptive may reduce the risk of breast cancer. Estrogens used in postmenopausal hormone replacement therapy increase the risk of both breast and endometrial cancer, but addition of a progestagen may counteract the increased risk to the endometrium. The agent most intensively under study for breast cancer prevention is tamoxifen, which has proven effectiveness as a therapeutic agent. When taken for more than two years it has been shown to reduce the occurrence of new contralateral tumours by about 50% in women who have had breast cancer. Three large international trials are currently evaluating its role in a preventive setting. For men, interest has centred on the use of 5 alpha-reductase inhibitors to block the prostatic conversion of testosterone to dehydrotestosterone and potentially inhibit the development of prostate cancer. The 5 alpha-reductase inhibitor finasteride is currently under test in a prevention trial.
许多最常见的癌症发生在受类固醇性激素激素调节的部位。对于女性来说，这些部位包括乳房、卵巢、子宫内膜，可能还包括结肠；对于男性来说，则包括前列腺和睾丸。由于使用雌激素和孕激素进行避孕或绝经后激素替代疗法，已经间接积累了许多关于这些癌症化学预防的信息。基于雌激素的避孕药显然能降低卵巢癌风险，但如果没有孕激素的拮抗作用，会增加子宫内膜癌风险。孕激素可降低子宫内膜癌风险，在绝经前使用时似乎能够抵消该部位外源性雌激素的致癌作用。口服避孕药对乳腺癌的影响似乎很小，但年轻时长期服用可能会增加风险。最近的研究表明，使用促黄体生成素释放激素激动剂作为避孕药可能会降低乳腺癌风险。绝经后激素替代疗法中使用的雌激素会增加乳腺癌和子宫内膜癌的风险，但添加孕激素可能会抵消子宫内膜癌风险的增加。正在进行最深入研究的预防乳腺癌的药物是他莫昔芬，它已被证明是一种有效的治疗药物。对于患有乳腺癌的女性，服用两年以上已被证明可使对侧新肿瘤的发生率降低约50%。目前有三项大型国际试验正在评估其在预防方面的作用。对于男性，人们的兴趣集中在使用5α-还原酶抑制剂来阻断睾酮向脱氢睾酮的前列腺转化，并可能抑制前列腺癌的发展。5α-还原酶抑制剂非那雄胺目前正在一项预防试验中进行测试。
