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[乳腺癌激素治疗的前景]

[Perspectives for the hormonal therapy of breast cancer].

作者信息

Eckhardt Sándor

机构信息

Országos Onkológiai Intézet, Budapest 1122, Hungary.

出版信息

Magy Onkol. 2003;47(2):133-40. Epub 2003 Sep 16.

Abstract

The role of estrogens, including its sources, tissue distribution, metabolism, and mechanism of action, is discussed in this review. The ER alpha and beta are functioning separately, and there is a physiological balance between their activity. Whenever this balance is over thrown due to endogenous or exogenous carcinogenic factors, malignancy develops. Risk factors of breast cancer are listed and evaluated individually. It should be stressed however, that their carcinogenic effect sums up. The knowledge of established risk factors rises the possibility of chemoprevention, which might be highly desirable in case of gene carriers. Special emphasis is attached to the SERM molecules which act as antiestrogens. Their antitumour effect is largely used in the treatment of hormone sensitive advanced breast cancer patients, and their efficacy has been proved in adjuvant therapy as well. Their preventive use might also be justified, especially in gene carriers. Aromatase inhibitors form a special class among the SERM molecules. In Hungary, anastrozole, letrozole and exemestane are widely applied for the therapy of breast cancer patients, while raloxifene has only been introduced recently, mainly in order to prevent osteoporosis. The therapeutic value of fulvestrant is unknown yet and its antitumour effect has to be explored. The therapeutic significance of these molecules lies in the fact that they might be effective after the development of tamoxifen resistance. There are several explanations for this phenomenon offering new targets for the further development of a succesful antitumour chemotherapy.

摘要

本综述讨论了雌激素的作用,包括其来源、组织分布、代谢及作用机制。雌激素受体α和β发挥着不同的功能,它们的活性之间存在生理平衡。当这种平衡因内源性或外源性致癌因素而被打破时,就会发生恶性肿瘤。乳腺癌的危险因素被逐一列出并评估。然而,应该强调的是,它们的致癌作用是累积的。对已确定危险因素的了解增加了化学预防的可能性,这对于基因携带者来说可能是非常可取的。特别强调了作为抗雌激素起作用的选择性雌激素受体调节剂(SERM)分子。它们的抗肿瘤作用在激素敏感性晚期乳腺癌患者的治疗中被大量使用,并且其疗效在辅助治疗中也得到了证实。它们的预防性使用也可能是合理的,尤其是在基因携带者中。芳香酶抑制剂在SERM分子中属于特殊类别。在匈牙利,阿那曲唑、来曲唑和依西美坦被广泛应用于乳腺癌患者的治疗,而雷洛昔芬最近才被引入,主要用于预防骨质疏松症。氟维司群的治疗价值尚不清楚,其抗肿瘤作用有待探索。这些分子的治疗意义在于,它们可能在他莫昔芬耐药后仍然有效。对于这一现象有多种解释,为成功的抗肿瘤化疗的进一步发展提供了新的靶点。

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