Tormey D C, Gray R, Falkson H C
AMC Cancer Research Center, Denver, CO 80214, USA.
J Natl Cancer Inst. 1996 Dec 18;88(24):1828-33. doi: 10.1093/jnci/88.24.1828.
Data from a pilot study published in 1984 suggested that tamoxifen administration (as adjuvant hormonal therapy) for more than 5 years after initial breast cancer surgery might have therapeutic benefit.
A randomized trial was performed to assess the efficacy of maintaining tamoxifen therapy beyond 5 years in women with axillary lymph node-positive breast cancer who had been treated with surgery followed by 1 year of chemotherapy and 5 years of tamoxifen.
One hundred ninety-four women (87 postmenopausal and 107 premenopasual) enrolled in two concurrent Eastern Cooperative Oncology Group adjuvant trials (E4181 for postmenopausal patients and E5181 for premenopausal patients) were randomly assigned to continued tamoxifen therapy or observation. Data for 193 women (87 postmenopausal and 106 premenopausal) were available for analysis. Median follow-up is 5.6 years since the randomization at 5 years, with the longest follow-up being 8.0 years. The major analyses measured events from the time of randomization until relapse or death; these included time-to-relapse analyses, with new opposite-breast cancers counted as treatment failures, and survival analyses. Time-to-relapse comparisons and survival comparisons for women in the two treatment groups were made by use of the Kaplan-Meier method and the logrank test. Reported P values are two-sided.
Five years after the randomization, no statistically significant differences were noted in either time to relapse or survival between women continuing to receive tamoxifen and those on observation. Eight-five percent of the women receiving tamoxifen were disease free at this time compared with 73% of those on observation (P = .10); survival was 86% for those continuing to receive tamoxifen and 89% for those on observation (P = .52). Differences in the time to relapse and survival between premenopausal and postmenopausal women assigned to the two treatment groups were also not statistically significant (time to relapse: P = .38 and P = .16 for premenopausal and postmenopausal patients, respectively; survival; P = .18 and P = .72 for premenopausal and postmenopausal patients, respectively). There was an indication that women with estrogen receptor-positive tumors may experience a longer time to relapse with continued tamoxifen therapy (P = .014); however, the survival difference for this subgroup was not statistically significant (P = .81). The toxicity patterns in the two treatment groups were similar.
Our results suggest that further evaluation of adjuvant tamoxifen therapy beyond 5 years in women with axillary lymph node-positive, estrogen receptor-positive breast cancer who have also been treated with adjuvant chemotherapy would be appropriate.
1984年发表的一项初步研究数据表明，在初次乳腺癌手术后服用他莫昔芬（作为辅助激素治疗）超过5年可能具有治疗益处。
进行一项随机试验，以评估在接受手术、1年化疗和5年他莫昔芬治疗的腋窝淋巴结阳性乳腺癌女性中，将他莫昔芬治疗延长至5年以上的疗效。
194名女性（87名绝经后女性和107名绝经前女性）参加了两项同时进行的东部肿瘤协作组辅助试验（绝经后患者为E4181试验，绝经前患者为E5181试验），被随机分配至继续他莫昔芬治疗组或观察组。193名女性（87名绝经后女性和106名绝经前女性）的数据可用于分析。自随机分组5年后的中位随访时间为5.6年，最长随访时间为8.0年。主要分析测量从随机分组时起至复发或死亡的事件；这些分析包括复发时间分析（将对侧新发乳腺癌视为治疗失败）和生存分析。使用Kaplan-Meier方法和对数秩检验对两个治疗组女性的复发时间和生存情况进行比较。报告的P值为双侧。
随机分组5年后，继续接受他莫昔芬治疗的女性与观察组女性在复发时间或生存率方面均未观察到统计学上的显著差异。此时，接受他莫昔芬治疗的女性中有85%无疾病，而观察组为73%（P = 0.10）；继续接受他莫昔芬治疗的女性生存率为86%，观察组为89%（P = 0.52）。分配至两个治疗组的绝经前和绝经后女性在复发时间和生存率方面的差异也无统计学意义（复发时间：绝经前和绝经后患者分别为P = 0.38和P = 0.16；生存率：绝经前和绝经后患者分别为P = 0.18和P = 0.72）。有迹象表明，雌激素受体阳性肿瘤女性继续接受他莫昔芬治疗可能复发时间更长（P = 0.014）；然而，该亚组的生存差异无统计学意义（P = 0.81）。两个治疗组的毒性模式相似。
我们的结果表明，对于已接受辅助化疗的腋窝淋巴结阳性、雌激素受体阳性乳腺癌女性，进一步评估5年以上的辅助他莫昔芬治疗是合适的。
