J Natl Cancer Inst. 1996 Nov 6;88(21):1543-9. doi: 10.1093/jnci/88.21.1543.
Postsurgical treatment with tamoxifen has been shown to improve overall survival among patients with early stage breast cancer. However, the optimal duration of tamoxifen treatment remains controversial.
A multicenter, randomized trial was initiated in Sweden in the early 1980s to compare 2 years with 5 years of adjuvant tamoxifen in the treatment of postmenopausal women younger than 75 years of age who had early stage, axillary lymph node-negative or -positive, invasive disease.
The trial was planned and organized by the Swedish Breast Cancer Group, and it involved five regional breast cancer study organizations (South Sweden, South-East Sweden, Stockholm, Uppsala-Orebro, and North Sweden). During the period from 1983 through 1991, a total of 3887 patients were entered in the trial; 3545 (91%) women remained alive and recurrence free at 2 years and could thus contribute meaningful information to the 2-year (n = 1801) versus 5-year (n = 1744) comparison. Primary surgery consisted of either modified radical mastectomy or breast-conserving surgery. Radiation therapy was indicated for patients with lymph node-positive disease and was generally offered to all women who were treated with breast-conserving surgery. Only 89 (2.5%) of the 3545 women who were recurrence free at 2 years received adjuvant chemotherapy concurrently with tamoxifen. Twenty-milligram daily doses of tamoxifen were used at two centers, and 40-mg daily doses were used at the remaining three centers. Estrogen receptor status of the tumor was known for 2987 women (77% of the entered patients). Primary end points in the trial were event-free survival (local-regional recurrence, distant metastasis, contralateral breast cancer, or death) and overall survival. Survival curves were estimated by use of the life-table method. The Cox proportional hazards model was used to make comparisons between the 2- and 5-year treatment groups.
Patients assigned to receive 5 years of tamoxifen, compared with 2 years of tamoxifen, experienced statistically significant improvements in event-free survival (relative hazard = 0.82; 95% confidence interval [CI] = 0.71-0.96) and overall survival (relative hazard = 0.82; 95% CI = 0.69-0.99). These findings translate into an 18% relative reduction in both first events (95% CI = 4%-29%) and mortality (95% CI = 1%-31%) with the longer treatment. Overall survival at 10 years was estimated to be 80% among patients in the 5-year tamoxifen group who were alive and recurrence free at 2 years, compared with 74% among corresponding patients in the 2-year treatment group. The benefit associated with the longer treatment extended to women with lymph node-positive as well as lymph node-negative disease, but it appeared to be restricted to women whose tumors were classified as estrogen receptor positive.
Five years of adjuvant tamoxifen is more beneficial than 2 years in the treatment of postmenopausal women with estrogen receptor-positive, early stage, invasive breast cancer.
已证明他莫昔芬术后治疗可提高早期乳腺癌患者的总生存率。然而，他莫昔芬治疗的最佳持续时间仍存在争议。
20世纪80年代初在瑞典启动了一项多中心随机试验，比较2年与5年辅助性他莫昔芬治疗75岁以下绝经后早期、腋窝淋巴结阴性或阳性浸润性疾病女性的效果。
该试验由瑞典乳腺癌研究小组规划和组织，涉及五个地区性乳腺癌研究机构（瑞典南部、瑞典东南部、斯德哥尔摩、乌普萨拉 - 厄勒布鲁和瑞典北部）。在1983年至1991年期间，共有3887例患者进入试验；3545例（91%）女性在2年时仍存活且无复发，因此可为2年（n = 1801）与5年（n = 1744）的比较提供有意义的信息。初次手术包括改良根治性乳房切除术或保乳手术。淋巴结阳性疾病患者需接受放射治疗，接受保乳手术的所有女性通常也会接受放疗。在2年时无复发的3545例女性中，只有89例（2.5%）在接受他莫昔芬治疗的同时接受了辅助化疗。两个中心使用每日20毫克的他莫昔芬剂量，其余三个中心使用每日40毫克的剂量。已知2987例女性（占入组患者的77%）肿瘤的雌激素受体状态。试验的主要终点是无事件生存期（局部区域复发、远处转移、对侧乳腺癌或死亡）和总生存期。生存曲线采用寿命表法估计。使用Cox比例风险模型对2年和5年治疗组进行比较。
与接受2年他莫昔芬治疗的患者相比，接受5年他莫昔芬治疗的患者在无事件生存期（相对风险 = 0.82；95%置信区间[CI] = 0.71 - 0.96）和总生存期（相对风险 = 0.82；95%CI = 0.69 - 0.99）方面有统计学显著改善。这些结果意味着，较长疗程的治疗使首次事件（95%CI = 4% - 29%）和死亡率（95%CI = 1% - 31%）相对降低18%。在2年时存活且无复发的5年他莫昔芬治疗组患者中，估计10年总生存率为80%，而2年治疗组的相应患者为74%。与较长疗程治疗相关的益处扩展至淋巴结阳性和阴性疾病的女性，但似乎仅限于肿瘤分类为雌激素受体阳性的女性。
对于雌激素受体阳性、早期浸润性乳腺癌的绝经后女性，5年辅助性他莫昔芬治疗比2年更有益。
