Lancet. 1992 Jan 4;339(8784):1-15.
In a worldwide collaboration, information was sought and centrally checked on mortality and recurrence for each woman in any randomised trial that began before 1985 of any aspect of systemic adjuvant therapy for early breast cancer. Checked data were available for 75,000 women (about 90% of those ever randomised), of whom 32% had died and another 10% had experienced recurrence. The parts now reviewed include 30,000 women in tamoxifen trials, 3000 in ovarian ablation trials, 11,000 in polychemotherapy trials, 15,000 in other chemotherapy comparisons, and 6000 in immunotherapy trials. Highly significant reductions in the annual rates both of recurrence and of death are produced by tamoxifen (25% SD 2 recurrence and 17% SD 2 mortality: 2p less than 0.00001), by ablation below age 50 (26% SD 6 recurrence and 25% SD 7 mortality: 2p = 0.0004), and by polychemotherapy (28% SD 3 recurrence and 16% SD 3 mortality: 2p less than 0.00001), but not by ablation at older ages or by immunotherapy. (Tamoxifen also reduced the risk of development of contralateral breast cancer by 39% SD 9: 1p less than 0.00001). For tamoxifen and for polychemotherapy the avoidance of recurrence is chiefly during years 0-4 (this difference being maintained but not increased afterwards), but the avoidance of mortality is highly significant both during and after years 0-4, so the cumulative differences in survival produced by these relatively brief treatments (median: 2 years tamoxifen, 1 year polychemotherapy) are larger at 10 than at 5 years. There is little information beyond year 10 (except for ovarian ablation, which produces separately significant mortality reductions both during and after years 0-9). Both direct and indirect randomised comparisons show long-term polychemotherapy (eg, 12 months) to be no better than shorter (eg, 6 months) regimens, but do show polychemotherapy to be significantly better than single-agent chemotherapy. Indirect randomised comparisons do not reveal significant differences between different forms of polychemotherapy, or differences between different tamoxifen doses, but do show that long-term tamoxifen (eg, 2 years, or even 5 years) is significantly more effective than shorter tamoxifen regimens. In old age (70+) tamoxifen is of demonstrated efficacy, but chemotherapy has not been evaluated. Between ages 50 and 69 direct comparisons show that chemotherapy plus tamoxifen is better (1p less than 0.00001) than chemotherapy alone both for recurrence and for mortality, and better (1p less than 0.00001) than tamoxifen alone for recurrence.(ABSTRACT TRUNCATED AT 400 WORDS)
在一项全球合作中，研究人员收集了1985年以前开始的关于早期乳腺癌全身辅助治疗任何方面的随机试验中每位女性的死亡率和复发率信息，并进行集中核查。核查数据涵盖了75000名女性（约占所有随机分组女性的90%），其中32%已死亡，另有10%经历了复发。目前回顾的部分包括30000名接受他莫昔芬试验的女性、3000名接受卵巢去势试验的女性、11000名接受多药化疗试验的女性、15000名参与其他化疗对照试验的女性以及6000名接受免疫治疗试验的女性。他莫昔芬可使复发率和死亡率的年发生率显著降低（复发率降低25%，标准差为2；死亡率降低17%，标准差为2：P值小于0.00001），50岁以下进行卵巢去势也有显著效果（复发率降低26%，标准差为6；死亡率降低25%，标准差为7：P值 = 0.0004），多药化疗同样如此（复发率降低28%，标准差为3；死亡率降低16%，标准差为3：P值小于0.00001），但年龄较大时进行卵巢去势或免疫治疗则无此效果。（他莫昔芬还使对侧乳腺癌的发病风险降低了39%，标准差为9：P值小于0.00001）。对于他莫昔芬和多药化疗，复发的避免主要在0至4年期间（之后这种差异保持但未增大），但死亡率的避免在0至4年期间及之后均非常显著，因此这些相对短期治疗（他莫昔芬中位治疗时间为2年，多药化疗为1年）所产生的生存累积差异在10年时比在5年时更大。10年之后的信息较少（卵巢去势除外，其在0至9年期间及之后均分别显著降低了死亡率）。直接和间接随机对照比较均显示，长期多药化疗（如12个月）并不比短期（如6个月）方案更好，但多药化疗明显优于单药化疗。间接随机对照比较未发现不同形式的多药化疗之间存在显著差异，也未发现不同他莫昔芬剂量之间存在差异，但显示长期他莫昔芬（如2年，甚至5年）比短期他莫昔芬方案显著更有效。在老年（70岁及以上），他莫昔芬已证明有效，但化疗尚未进行评估。在50至69岁之间，直接比较表明，化疗加他莫昔芬在复发率和死亡率方面均优于单纯化疗（P值小于0.00001），在复发率方面也优于单纯他莫昔芬（P值小于0.00001）。（摘要截取自400字）
