Tagnon H J
Cancer. 1977 Jun;39(6 Suppl):2959-64. doi: 10.1002/1097-0142(197706)39:6<2959::aid-cncr2820390682>3.0.co;2-2.
The antiestrogens represent a group of compounds, not necessarily steroidal, which are able to decrease the specific uptake of estrogens in vitro and in vivo by various target tissues in the rat and in man. This action is explained either by competitive binding to estrogen receptor sites or, more probably, by failure of the antiestrogen complex, translocated into the nucleus, to stimulate neoformation of receptors in the cytoplasm. This explains the transient estrogenic effect of antiestrogen. Antiestrogens used in humans are hormone specific and antagonize also non-steroidal estrogens, like stilbestrol. Three compounds have been used in advanced breast cancer with the same indications as the older hormonal treatments. They are clomiphene citrate, nafoxidine and tamoxifen. Nafoxidine and tamoxifen are probably equally active. The response rate is between 28 and 35%, with a median duration of nine months. Nafoxidine is toxic for the skin and tamoxifen is the preferred compound. A randomized trial comparing ethinyl estradiol and an antiestrogen showed similar rates of response with the two compounds in advanced breast cancer. The uniformity of results of treatment of advanced breast cancer by hormonal agents including antiestrogens and their limitations, probably justifies the present-day concept which assigns hormonal treatment a secondary role, either as a supplement to cytotoxic chemotherapy or for old and debilitated patients. However, as a supplemented to chemotherapy, hormonal agents are probably important since recent studies have shown that apparently all breast cancers have positive receptor sites, albeit in variable amounts. Because of their lack of toxicity, antiestrogens are probably the best hormonal agents available at present.
抗雌激素药物是一类化合物，不一定是甾体类，它们能够在体外和体内降低大鼠和人体各种靶组织对雌激素的特异性摄取。这种作用要么是通过与雌激素受体位点竞争性结合来解释，要么更可能是由于转运到细胞核中的抗雌激素复合物未能刺激细胞质中受体的重新形成。这就解释了抗雌激素的短暂雌激素效应。用于人类的抗雌激素药物具有激素特异性，也能拮抗非甾体雌激素，如己烯雌酚。有三种化合物已用于晚期乳腺癌，其适应证与较老的激素治疗相同。它们是枸橼酸氯米芬、萘福昔定和他莫昔芬。萘福昔定和他莫昔芬可能具有同等活性。缓解率在28%至35%之间，中位持续时间为9个月。萘福昔定对皮肤有毒性，他莫昔芬是首选化合物。一项比较炔雌醇和一种抗雌激素的随机试验表明，在晚期乳腺癌中，这两种化合物的缓解率相似。包括抗雌激素药物在内的激素制剂治疗晚期乳腺癌的结果的一致性及其局限性，可能证明了目前将激素治疗视为次要作用的观念是合理的，要么作为细胞毒性化疗的补充，要么用于老年和体弱患者。然而，作为化疗的补充，激素制剂可能很重要，因为最近的研究表明，显然所有乳腺癌都有阳性受体位点，尽管数量各不相同。由于抗雌激素药物没有毒性，它们可能是目前可用的最好的激素制剂。
