J Natl Cancer Inst. 1996 Dec 18;88(24):1834-9. doi: 10.1093/jnci/88.24.1834.
Although trials of post-surgical tamoxifen therapy for patients with breast cancer have convincingly demonstrated reductions in relapse rates and improvements in survival, the optimal duration of therapy is as yet unclear.
Our objective is to determine whether 2 or 5 years of tamoxifen therapy (20 mg/day orally) is preferable in the treatment of patients with early breast cancer.
A randomized trial that was pragmatic in policy, allowing flexibility in primary treatment (i.e., type of surgery) and adjuvant therapy other than tamoxifen (i.e., radiotherapy or chemotherapy), was used to encourage maximum participation of clinicians and patients. This design allowed comparison of the two durations of tamoxifen therapy under conditions in which they would subsequently be applied in clinical practice. The patients were recruited from the oncology departments of participating hospitals in the U.K., Belgium, Poland, and Hong Kong. Those women who had completed an initial 2-year course of tamoxifen therapy after primary surgery and had not experienced a recurrence of breast cancer were asked to consider random assignment either to no further therapy or to an additional 3 years of tamoxifen. Follow-up reports (every 6 months for 3 years after random assignment and then annually) were required for all surviving study subjects. These reports recorded all breast cancer-related events (i.e., locoregional relapse and distant metastasis) or the development of new primary tumors (in the opposite breast or at any other site). For patients who died, the date and cause of death were recorded. Event-free survival; overall survival; and time to locoregional relapse, distant metastasis, or the development of new primary cancers were end points for the analysis. Survival comparisons were made by use of life tables and the logrank test. Reported P values are two-sided.
By December 31, 1994, 2937 patients had accepted random assignment to treatment; 1470 were assigned to stop tamoxifen therapy after having received it for 2 years and 1467 were assigned to continue therapy for an additional 3 years (total, 5 years). An analysis was performed when the target for patient accrual had been reached, although the trial remains open. At a median follow-up of 2 years since the randomization, no difference in survival between the two treatment groups was detected (relative risk = 0.89; 95% confidence interval = 0.69-1.15), but a statistically significant delay in the time to relapse for patients receiving the longer treatment was demonstrated (relative risk = 0.81; 95% confidence interval = 0.69-0.98).
Our results suggest that 5 years may be better than 2 years of tamoxifen therapy, but more evidence regarding the optimal duration of tamoxifen therapy must be obtained.
尽管针对乳腺癌患者的术后他莫昔芬治疗试验已令人信服地证明复发率降低且生存率提高，但最佳治疗持续时间仍不清楚。
我们的目标是确定他莫昔芬治疗（口服20毫克/天）2年或5年对早期乳腺癌患者的治疗是否更优。
一项在政策上注重实效的随机试验，允许在主要治疗（即手术类型）和除他莫昔芬之外的辅助治疗（即放疗或化疗）方面具有灵活性，以此鼓励临床医生和患者最大限度地参与。这种设计允许在随后将应用于临床实践的条件下比较两种他莫昔芬治疗持续时间。患者从英国、比利时、波兰和香港参与研究的医院肿瘤科招募。那些在初次手术后完成了2年他莫昔芬初始疗程且未出现乳腺癌复发的女性被要求考虑随机分配至不再接受进一步治疗或再接受3年他莫昔芬治疗。所有存活的研究对象均需进行随访报告（随机分配后每6个月报告3年，之后每年报告）。这些报告记录了所有与乳腺癌相关的事件（即局部区域复发和远处转移）或新原发性肿瘤的发生（在对侧乳房或其他任何部位）。对于死亡患者，记录死亡日期和原因。无事件生存期、总生存期以及局部区域复发时间、远处转移时间或新原发性癌症发生时间为分析的终点。通过生命表和对数秩检验进行生存比较。报告的P值为双侧。
截至1994年12月31日，2937例患者接受了随机分配治疗；1470例被分配在接受他莫昔芬治疗2年后停止治疗，1467例被分配继续治疗3年（总计5年）。在达到患者入组目标时进行了分析，尽管试验仍在进行。随机分组后中位随访2年时，未检测到两个治疗组之间的生存差异（相对风险 = 0.89；95%置信区间 = 0.69 - 1.15），但接受较长疗程治疗的患者复发时间有统计学意义的延迟（相对风险 = 0.81；95%置信区间 = 0.69 - 0.98）。
我们的结果表明，他莫昔芬治疗5年可能优于2年，但必须获得更多关于他莫昔芬治疗最佳持续时间的证据。
