MacMahon B
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02192-3115, USA.
Semin Oncol. 1997 Feb;24(1 Suppl 1):S1-122-S1-39.
The epidemiologic studies relevant to the hypothesis that exposure to tamoxifen is associated with risk of cancer of the endometrium and perhaps other organs are described, summarized, and evaluated. One large body of data comes from the randomized trials of tamoxifen as a therapeutic agent against established breast cancer. With respect to endometrial cancer, these studies suggest that an association with tamoxifen use exists. However, the evidence is far from conclusive: the association is not seen in all the reported randomized trials, there appears to be a deficit of endometrial cancer in the comparison groups in two of the most important studies, none of the studies has adequately addressed the problems of confounding by prior hysterectomy and/or hormone replacement therapy, and none addresses the issue of detection bias. One nonrandomized cohort study shows findings similar to those from the randomized studies but also has similar problems, in addition to the problems associated with the lack of randomization of exposure. Case control studies were also considered, with the conclusion that they show results similar to those from the cohort studies (randomized and nonrandomized); that is, that the evidence leans toward the view that there is an association between tamoxifen use and endometrial cancer risk, but that it is incomplete and inconclusive. The issues of detection bias and potential confounding variables are better dealt with in the case control studies than in the cohort studies. One important question raised in one of the major case control studies is whether the apparent association is stronger with total dose of tamoxifen or with duration of use. Some investigators have reported an association between tamoxifen use and cancers other than those of the endometrium, but for none of these cancers is the evidence consistent between studies and the associations lack the theoretical underpinning that might be invoked for endometrial cancer, if in fact the existence of an association were established empirically for the latter site.
本文描述、总结并评估了与他莫昔芬暴露与子宫内膜癌及其他器官癌症风险相关假说的流行病学研究。大量数据来自他莫昔芬作为治疗已确诊乳腺癌的治疗药物的随机试验。关于子宫内膜癌，这些研究表明他莫昔芬的使用与之存在关联。然而，证据远非确凿：并非所有报告的随机试验中都能看到这种关联，在两项最重要的研究中，对照组的子宫内膜癌似乎有所不足，没有一项研究充分解决了既往子宫切除术和/或激素替代疗法造成的混杂问题，也没有一项研究解决检测偏倚问题。一项非随机队列研究显示的结果与随机研究相似，但也存在类似问题，此外还存在暴露缺乏随机性的相关问题。还考虑了病例对照研究，其结论是，这些研究显示的结果与队列研究（随机和非随机）相似；也就是说，证据倾向于认为他莫昔芬的使用与子宫内膜癌风险之间存在关联，但证据不完整且不确定。病例对照研究比队列研究更好地处理了检测偏倚和潜在混杂变量的问题。一项主要病例对照研究中提出的一个重要问题是，这种明显的关联与他莫昔芬的总剂量还是使用持续时间更强。一些研究人员报告了他莫昔芬的使用与子宫内膜癌以外的其他癌症之间的关联，但对于这些癌症中的任何一种，研究之间的证据都不一致，而且这些关联缺乏如果事实上通过经验确定了子宫内膜癌存在关联时可能援引的理论基础。
