Chlebowski R T, Butler J, Nelson A, Lillington L
UCLA School of Medicine, Department of Medicine, Torrance.
Cancer. 1993 Aug 1;72(3 Suppl):1032-7. doi: 10.1002/1097-0142(19930801)72:3+<1032::aid-cncr2820721315>3.0.co;2-o.
Intervention clinical trials are under way to address whether tamoxifen can prevent breast cancer development. This effort is based on laboratory evidence that tamoxifen interferes with the initiation and promotion of mammary cancer, clinical evidence of decreased breast cancer incidence in the opposite breast of women participating in tamoxifen adjuvant breast cancer trials, and a favorable toxicity profile of tamoxifen providing reasonable assurance of drug safety when used in a population without cancer. The apparently favorable effects of tamoxifen on lipid metabolism and bone mineral density provide additional impetus to this evaluation. Potentially life threatening toxicity of thromboembolism and development of a second cancer remain concerns. With respect to implications of such clinical trials, even upon successful study completion, difficult issues will remain; these issues include the potential for interaction between tamoxifen and dietary fat reduction (also proposed as potential breast cancer prevention), the cost and cost-effectiveness of wide scale (or selective) implementation of positive results, and the generalizability of study results to socioeconomically disadvantaged and racial and ethnic minority populations that historically have been under-represented in medical clinical trials. These important issues should be addressed concurrently as large-scale prevention trials go forward to optimize the practical utility of efficacy data obtained.
干预性临床试验正在进行，以探讨他莫昔芬是否能够预防乳腺癌的发生。这项工作基于以下几点：实验室证据表明他莫昔芬会干扰乳腺癌的起始和发展过程；参与他莫昔芬辅助性乳腺癌试验的女性对侧乳房患癌率降低的临床证据；以及他莫昔芬良好的毒性特征，这为在无癌症人群中使用该药时的药物安全性提供了合理保障。他莫昔芬对脂质代谢和骨密度的明显有益作用为这项评估提供了额外动力。血栓栓塞这一潜在的危及生命的毒性以及第二种癌症的发生仍然令人担忧。关于此类临床试验的影响，即使研究成功完成，难题依然存在；这些问题包括他莫昔芬与减少膳食脂肪（也被认为是潜在的乳腺癌预防措施）之间相互作用的可能性、大规模（或选择性）实施阳性结果的成本和成本效益，以及研究结果在社会经济地位不利群体和种族及少数族裔群体中的普遍性，而这些群体在医学临床试验中的代表性历来不足。随着大规模预防试验的推进，这些重要问题应同时得到解决，以优化所获疗效数据的实际效用。
