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[乳腺癌化学预防的突破]

[Breakthrough in breast cancer chemoprevention].

作者信息

Kahán Zsuzsanna, Thurzó László

机构信息

Szegedi Tudományegyetem, Altalános Orvostudományi Kar, Szent-Györgyi Albert Orvos- és Gyógyszerésztudományi Centrum Onkoterápiás Klinika.

出版信息

Orv Hetil. 2003 Mar 30;144(13):597-603.

Abstract

Breast cancer is the most frequent female malignant disease in developed countries. Various approaches are being developed for breast cancer prevention. Medical prevention called chemoprevention is reviewed. Prior to any intervention estimation of breast cancer risk is mandatory. For practical reasons distinction of two risk groups is useful. In the high risk group inherited gene mutation showing high penetrance may be suspected, while in the medium risk group hormonal factors play an important role. The antiestrogen tamoxifen has been extensively investigated in breast cancer and also tested for the prevention of breast cancer. The results of four randomized tamoxifen prevention studies have been published. In the largest, American trial the number of invasive or "in situ" breast cancers was halved by tamoxifen. Particularly estrogen receptor positive and relatively good prognosis breast cancers were reduced. Similar results were obtained in the "International Breast Intervention Study". Tamoxifen has been registered for breast cancer prevention for high risk individuals in the United States. The Italian and English ("Royal Marsden Hospital") studies did not prove significant preventative effect for tamoxifen that may be explained by the characteristics of the study protocols and study populations. Increased rates of endometrial cancer, thromboembolic events and cataract were observed under tamoxifen treatment, especially over the age of 50. Prevention has an increased importance in gene mutation carriers. Besides prophylactic mastectomy and close surveillance tamoxifen and bilateral oophorectomy or the use of gonadotropin releasing-hormone analogs seem efficient in this group. Various new chemoprevention strategies are under testing. Raloxifene and the aromatase inhibitors show advantage in menopausal women, the retinoid fenretinide and the gonadotropin releasing-hormone analogs seem promising for premenopausal individuals. The use of these agents are investigated in clinical trials. It is likely that not one single method will be applied for breast cancer prevention in the future. Preferably individual prevention strategies based on individual risk assessment will be developed.

摘要

在发达国家,乳腺癌是女性中最常见的恶性疾病。目前正在开发各种预防乳腺癌的方法。本文对称为化学预防的医学预防方法进行综述。在进行任何干预之前,必须对乳腺癌风险进行评估。出于实际原因,区分两个风险组是有用的。在高风险组中,可能怀疑存在具有高外显率的遗传性基因突变,而在中等风险组中,激素因素起重要作用。抗雌激素他莫昔芬已在乳腺癌研究中得到广泛研究,也被用于乳腺癌预防的测试。四项他莫昔芬预防随机研究的结果已经发表。在美国进行的最大规模试验中,他莫昔芬使浸润性或“原位”乳腺癌的数量减半。特别是雌激素受体阳性且预后相对较好的乳腺癌有所减少。在“国际乳腺干预研究”中也获得了类似结果。他莫昔芬已在美国被批准用于高危个体的乳腺癌预防。意大利和英国(“皇家马斯登医院”)的研究未证明他莫昔芬具有显著的预防效果,这可能由研究方案和研究人群的特点来解释。在他莫昔芬治疗下,尤其是50岁以上的患者,子宫内膜癌、血栓栓塞事件和白内障的发生率有所增加。对于基因突变携带者,预防更为重要。除了预防性乳房切除术和密切监测外,他莫昔芬、双侧卵巢切除术或使用促性腺激素释放激素类似物在该组中似乎有效。各种新的化学预防策略正在测试中。雷洛昔芬和芳香化酶抑制剂在绝经后女性中显示出优势,视黄酸类药物芬维A胺和促性腺激素释放激素类似物对绝经前个体似乎很有前景。这些药物的使用正在临床试验中进行研究。未来可能不会只采用单一方法来预防乳腺癌。最好是根据个体风险评估制定个性化的预防策略。

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