Hormonal Therapy and Chemoprevention
Hormonal Therapy and Chemoprevention
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激素治疗和化学预防
DOI：
10.1046/j.1524-4741.2000.20064.x
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
A. Decensi
中科院分区：
文献类型：
--
作者：
B. Bonanni;A. Guerrieri;N. Rotmensz;R. Torrisi;F. Pigatto;M. Cazzaniga;S. Mora;S. Diani;C. Robertson;A. Decensi
摘要：激素替代疗法（HRT）可以提高生活质量和寿命，但长期使用也会增加患乳腺癌的风险。HRT和选择性雌激素受体调节剂（SERM）（如他莫昔芬）的组合可以保留益处，同时降低任何一种药物的风险。意大利他莫昔芬预防研究的事后分析显示，与接受安慰剂的连续HRT使用者相比，连续接受HRT和他莫昔芬的女性乳腺癌发生率显著降低。最近的研究表明，他莫昔芬的标准剂量可以减少到四分之一（即，每隔一天10毫克），而不会失去其有益的生物效应。由于他莫昔芬的子宫内膜效应似乎是剂量和时间依赖性的，因此减少剂量可以大大降低子宫内膜癌的风险，同时保持其预防功效。另一方面，添加含有孕激素的HRT也可以最大限度地降低与他莫昔芬相关的子宫内膜癌的风险。此外，雌激素应该减少血管扩张和泌尿生殖系统症状的发生率，这是预防研究中他莫昔芬停药的主要原因。值得注意的是，在国家外科辅助乳腺项目（NSABP）P-1试验中，50岁或以下的女性不良事件的发生率没有增加，包括子宫内膜癌和静脉血栓栓塞事件。对绝经前无毒性的一个可能解释是存在足够的循环雌激素水平，这阻止了他莫昔芬在这些靶组织中作为雌激素激动剂。此外，来自当前意大利他莫昔芬预防试验的数据表明，与研究期间从未接受HRT的女性相比，从头开始和当前HRT使用者的依从性显著更高。因此，HRT和他莫昔芬在低剂量下的组合可以降低风险和副作用，同时保留任何一种药物的益处。
Abstract: Hormone replacement therapy (HRT) can increase the quality as well as the length of life, but a prolonged use can also increase the risk of breast cancer. The combination of HRT and a selective estrogen receptor modulator (SERM) such as tamoxifen may retain the benefits while reducing the risks of either agent. A post hoc analysis of the Italian Tamoxifen Prevention Study showed a borderline significant reduction of breast cancer among women who were on HRT continuously and tamoxifen as compared with continuous HRT users who received placebo. Recent studies suggest that the standard dose of tamoxifen may be reduced to one‐quarter (i.e., 10 mg every other day) without loss of its beneficial biological effects. Since the endometrial effect of tamoxifen seems to be both dose and time dependent, a dose reduction could substantially reduce the risk of endometrial cancer while retaining its preventive efficacy. On the other hand, the addition of HRT containing progestins could also minimize the risk of endometrial cancer associated with tamoxifen. Moreover, estrogen should reduce the incidence of vasomotor and urogenital symptoms, which are a major reason for tamoxifen withdrawal in prevention studies. Notably, in the National Surgical Adjuvant Breast Project (NSABP) P‐1 trial, women ages 50 or younger had no increased incidence of adverse events, including endometrial cancer and venous thromboembolic events. One possible explanation for the lack of toxicity in premenopause is the presence of adequate circulating estrogen levels which prevent tamoxifen to act as an estrogen agonist at these target tissues. Moreover, data from the current Italian tamoxifen prevention trial indicate that the compliance was substantially higher for de novo and current HRT users as compared to women who never received HRT during the study. The combination of HRT and tamoxifen at low doses could thus reduce the risks and side effects while retaining the benefits of either agent.
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DOI：
10.1097/00006254-199202000-00027
发表时间：
1991-09
期刊：
The New England journal of medicine
影响因子：
--
作者：
M. Stampfer;G. Colditz;W. Willett;J. Manson;B. Rosner;F. Speizer;C. Hennekens
通讯作者：
M. Stampfer;G. Colditz;W. Willett;J. Manson;B. Rosner;F. Speizer;C. Hennekens
DOI：
10.1097/00006254-200007000-00022
发表时间：
2000-02
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
R. Ross;A. Paganini-Hill;Peggy Wan;M. Pike
通讯作者：
R. Ross;A. Paganini-Hill;Peggy Wan;M. Pike
非甾体抗雌激素抑制人乳腺癌细胞生长的机制。
DOI：
10.1016/0022-4731(87)90165-8
发表时间：
1987
期刊：
Journal of steroid biochemistry
影响因子：
--
作者：
Sutherland,RL;Watts,CK;Hall,RE;Ruenitz,PC
通讯作者：
Ruenitz,PC
DOI：
10.1093/jnci/91.3.264
发表时间：
1999-02-03
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Schairer, C;Gail, M;Hoover, RN
通讯作者：
Hoover, RN
DOI：
10.1097/00006254-200006000-00022
发表时间：
2000-01
期刊：
JAMA
影响因子：
--
作者：
C. Schairer;J. Lubin;R. Troisi;S. Sturgeon;L. Brinton;R. Hoover
通讯作者：
C. Schairer;J. Lubin;R. Troisi;S. Sturgeon;L. Brinton;R. Hoover