Charlier C, Colin C, Merville M P, Gielen J, Lambotte R, Plomteux G, Castronovo V
Laboratoire de Recherche sur les Métastases, Université de Liège, Belgique.
J Gynecol Obstet Biol Reprod (Paris). 1994;23(7):751-6.
Tamoxifen is the most often prescribed non steroidal antioestrogenic agent in the world for breast cancer. Worldwide collaboration. has centralized the results, of different trials throughout the world on oral adjuvant therapy in the early stages of breast cancer. A significative regression of the tumour was observed in most cases. Moreover, recent epidemiological studies suggest that tamoxifen could prevent new contralateral primary tumours. The risk of the disease should thus be reduced by the prophylactic use of antioestrogens such as tamoxifen. Investigations using a variety of models have evaluated the effect of tamoxifen on tumour promotion and cell growth. Tamoxifen-induced growth inhibition is associated with major changes in biochemical events in cultured human breast cancer cells including cell proliferation or growth factor production. Growth inhibition of oestrogen-responsive human breast cancer cells is associated with an induced secretion of autoinhibitory polypeptides (TGF beta) and an antagonistic effect on the synthesis of proliferative proteins (TGF alpha,...). The first step in the mechanism of action of the drug is binding of tamoxifen to the oestrogen receptors. Development of resistance to tamoxifen treatment is a great problem in treatment of breast cancer patients and the mechanism of resistance will require further study: under the influence of the drug, tumours could become remodelled as selected subpopulations emerge resistant-tamoxifen. The fact that some breast cancers which are oestrogen receptor-negative respond to antioestrogen suggests that parallel but separate pathways for oestrogen and antioestrogen action may exist. This paper summarizes the results of the most recent studies concerning this promising drug.
他莫昔芬是世界上治疗乳腺癌最常用的非甾体类抗雌激素药物。全球合作汇总了世界各地关于乳腺癌早期口服辅助治疗的不同试验结果。在大多数病例中观察到肿瘤有显著消退。此外，最近的流行病学研究表明，他莫昔芬可以预防新的对侧原发性肿瘤。因此，通过预防性使用他莫昔芬等抗雌激素药物，疾病风险应该会降低。使用多种模型的研究评估了他莫昔芬对肿瘤促进和细胞生长的影响。他莫昔芬诱导的生长抑制与培养的人乳腺癌细胞生化事件的重大变化有关，包括细胞增殖或生长因子产生。雌激素反应性人乳腺癌细胞的生长抑制与自抑制多肽（转化生长因子β）的诱导分泌以及对增殖蛋白（转化生长因子α等）合成的拮抗作用有关。该药物作用机制的第一步是他莫昔芬与雌激素受体结合。对他莫昔芬治疗产生耐药性是乳腺癌患者治疗中的一个重大问题，耐药机制需要进一步研究：在药物影响下，随着对他莫昔芬耐药的亚群出现，肿瘤可能会发生重塑。一些雌激素受体阴性的乳腺癌对抗雌激素有反应，这一事实表明雌激素和抗雌激素作用可能存在平行但独立的途径。本文总结了关于这种有前景药物的最新研究结果。
