Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C, Rotmensz N, Boyle P
European Institute of Oncology, Milan, Italy.
Lancet. 1998 Jul 11;352(9122):93-7. doi: 10.1016/s0140-6736(98)85011-3.
Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive.
In October, 1992, we started a double-blind placebo-controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy. Women were randomised to receive tamoxifen 20 mg per day or placebo, both orally for 5 years. The original plan was to follow the intervention phase by 5 years' follow-up. In June, 1997, the trialists and the data-monitoring committee decided to end recruitment primarily because of the number of women dropping out of the study. Recruitment ended on July 11, 1997, and the study will continue as planned. The primary endpoints are the occurrence of and deaths from breast cancer. This preliminary interim analysis is based on intention-to-treat.
5408 women were randomised; participating women have a median follow-up of 46 months for major endpoints. 41 cases of breast cancer occurred so far; there have been no deaths from breast cancer. There is no difference in breast-cancer frequency between the placebo (22 cases) and tamoxifen (19) arms. There is a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone-replacement therapy during the trial: among 390 women on such therapy and allocated to placebo, we found eight cases of breast cancer compared with one case among 362 women allocated to tamoxifen. Compared with the placebo group, there was a significantly increased risk of vascular events and hypertriglyceridaemia among women on tamoxifen.
Although this preliminary analysis has low power, in this cohort of women at low-to-normal risk of breast cancer, the postulated protective effects of tamoxifen are not yet apparent. Women using hormone-replacement therapy appear to have benefited from use of tamoxifen. There were no deaths from breast cancer recorded in women in the study. It is essential to continue follow-up to quantify the long-term risks and benefits of tamoxifen therapy.
他莫昔芬是一种乳腺癌化学预防的候选药物，尽管该药物可能与子宫内膜癌的发生有关。因此，我们在接受子宫切除术的女性中开展了一项他莫昔芬化学预防试验。
1992年10月，我们开始了一项双盲、安慰剂对照、随机试验，研究对象为未患乳腺癌且已接受子宫切除术的女性（主要在意大利）。女性被随机分配接受每日20毫克他莫昔芬或安慰剂，均口服5年。原计划在干预阶段后进行5年随访。1997年6月，试验人员和数据监测委员会决定主要因退出研究的女性数量而停止招募。招募于1997年7月11日结束，研究将按计划继续。主要终点是乳腺癌的发生和死亡情况。这项初步中期分析基于意向性分析。
5408名女性被随机分组；参与研究的女性主要终点的中位随访时间为46个月。到目前为止，发生了41例乳腺癌；尚无乳腺癌死亡病例。安慰剂组（22例）和他莫昔芬组（19例）的乳腺癌发生率无差异。在试验期间同时使用激素替代疗法的接受他莫昔芬治疗的女性中，乳腺癌有统计学显著减少：在390名接受此类疗法并被分配到安慰剂组的女性中，我们发现8例乳腺癌，而在362名被分配到他莫昔芬组的女性中为1例。与安慰剂组相比，接受他莫昔芬治疗的女性发生血管事件和高甘油三酯血症的风险显著增加。
尽管这项初步分析的效力较低，但在这个乳腺癌风险低至正常的女性队列中，他莫昔芬假定的保护作用尚不明显。使用激素替代疗法的女性似乎从他莫昔芬的使用中获益。研究中的女性未记录到乳腺癌死亡病例。继续随访以量化他莫昔芬治疗的长期风险和益处至关重要。
