Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors
Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors
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DOI：
10.1093/jnci/88.21.1529
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发表时间：
1996-11-06
影响因子：
10.3
通讯作者：
Lickley, HL
中科院分区：
文献类型：
--
作者：
Fisher, B;Dignam, J;Lickley, HL
背景资料：1982年，国家外科辅助乳腺和肠道项目启动了一项随机、双盲、安慰剂对照试验（B-14），以确定他莫昔芬辅助治疗对雌激素受体阳性且无腋窝淋巴结受累的原发性可手术乳腺癌患者的有效性。研究结果表明，他莫昔芬治疗为早期疾病患者提供了实质性的益处。然而，出现了一些问题，如观察到的获益将持续多久，维持最大获益所需的治疗持续时间，以及长期治疗不良反应的性质和严重程度。目的：我们评估了B-14试验中患者10年随访的结果。此外，还比较了他莫昔芬治疗5年与5年以上的疗效。方法：在试验中，患者最初被分配接受他莫昔芬20 mg/天（n = 1404）或安慰剂（n = 1414）。他莫昔芬治疗5年后仍无疾病的患者，然后重新分配接受另外5年的他莫昔芬（n = 322）或5年的安慰剂（n = 321）。研究开始后，另一组符合与随机分配患者相同的方案合格性要求的患者登记接受他莫昔芬治疗（n = 1211）。治疗5年后无疾病的登记患者也被随机分配到另一个5年的他莫昔芬（n = 261）或5年的安慰剂（n = 249）。为了比较5年与超过5个档位的他莫昔芬治疗，将所有重新分配到额外5年药物治疗的患者的相关数据合并。未重新分配至他莫昔芬或安慰剂组的患者继续接受研究随访。使用Kaplan-Meier方法估计生存期、无疾病生存期和无远处疾病生存期（与远处部位失败相关）;使用对数秩检验评估治疗组间差异。使用考克斯比例风险模型确定相对失效风险（95%置信区间[CI]）。报告的P值为双侧。结果：通过10年的随访，无病生存率明显高于无病生存率（69%对57%，P
Background: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. Purpose: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared. Methods: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 gears of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. Results: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P