Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes - The NSABP study of tamoxifen and raloxifene (STAR) P-2 trial
Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes - The NSABP study of tamoxifen and raloxifene (STAR) P-2 trial
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DOI：
10.1001/jama.295.23.joc60074
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发表时间：
2006-06-21
影响因子：
120.7
通讯作者：
Wolmark, Norman
中科院分区：
文献类型：
--
作者：
Vogel, Victor G.;Costantino, Joseph P.;Wolmark, Norman
背景 他莫昔芬被批准用于降低乳腺癌风险，而雷洛昔芬在患有骨质疏松症的老年女性的试验中已证明可降低乳腺癌风险。目的 比较雷洛昔芬和他莫昔芬对发展为浸润性乳腺癌和其他疾病结果的风险的相对效果和安全性。设计、设置和患者 他莫昔芬和雷洛昔芬试验的国家外科辅助乳腺和肠道项目研究，一项前瞻性、双盲、随机试验该临床试验于 1999 年 7 月 1 日开始在北美近 200 个临床中心进行，在诊断出至少 327 例浸润性乳腺癌后启动了最终分析。患者为 19 747 名平均年龄 58.5 岁的绝经后女性，其 5 年乳腺癌风险增加（平均风险为 4.03% [SD, 2.17%]）。报告的数据以 2005 年 12 月 31 日为截止日期。 干预 口服他莫昔芬（20 毫克/天）或雷洛昔芬（60 毫克/天）超过 5 年。主要结果指标 浸润性乳腺癌、子宫癌、非浸润性乳腺癌、骨折、血栓栓塞事件的发生率。结果 接受他莫昔芬治疗的女性中有 163 例患有浸润性乳腺癌，接受雷洛昔芬治疗的女性有 168 例（发病率，每 1000 人 4.30 例 vs 每 1000 人 4.41 例；风险比 [RR]，1.02；95% 置信区间） [CI]，0.82-1.28）。他莫昔芬组（57例）的非浸润性乳腺癌病例数少于雷洛昔芬组（80例）（发病率，1.51 vs 2.11/1000；RR，1.40；95% CI，0.98-2.00）。他莫昔芬治疗组有 36 例子宫癌病例，雷洛昔芬组有 23 例子宫癌病例（RR，0.62；95% CI，0.35-1.08）。对于其他浸润性癌症部位、缺血性心脏病事件或中风，没有发现差异。雷洛昔芬组血栓栓塞事件发生率较低（RR，0.70；95% CI，0.54-0.91）。各组骨质疏松性骨折的数量相似。服用雷洛昔芬的女性中，白内障（RR，0.79；95% CI，0.68-0.92）和白内障手术（RR，0.82；95% CI，0.68-0.99）的发生率较低。死亡总数（他莫昔芬 vs 雷洛昔芬 101 例 vs 雷洛昔芬 96 例）或死亡原因没有差异。 结论 雷洛昔芬在降低浸润性乳腺癌风险方面与他莫昔芬一样有效，血栓栓塞事件和白内障风险较低，但非浸润性乳腺癌风险较高，无统计学意义。这两种药物患其他癌症、骨折、缺血性心脏病和中风的风险相似。
Context Tamoxifen is approved for the reduction of breast cancer risk, and raloxifene has demonstrated a reduced risk of breast cancer in trials of older women with osteoporosis.Objective To compare the relative effects and safety of raloxifene and tamoxifen on the risk of developing invasive breast cancer and other disease outcomes.Design, Setting, and Patients The National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial, a prospective, double-blind, randomized clinical trial conducted beginning July 1, 1999, in nearly 200 clinical centers throughout North America, with final analysis initiated after at least 327 incident invasive breast cancers were diagnosed. Patients were 19 747 postmenopausal women of mean age 58.5 years with increased 5-year breast cancer risk ( mean risk, 4.03% [SD, 2.17%]). Data reported are based on a cutoff date of December 31, 2005.Intervention Oral tamoxifen ( 20 mg/d) or raloxifene ( 60 mg/d) over 5 years. Main Outcome Measures Incidence of invasive breast cancer, uterine cancer, non-invasive breast cancer, bone fractures, thromboembolic events.Results There were 163 cases of invasive breast cancer in women assigned to tamoxifen and 168 in those assigned to raloxifene ( incidence, 4.30 per 1000 vs 4.41 per 1000; risk ratio [RR], 1.02; 95% confidence interval [CI], 0.82-1.28). There were fewer cases of noninvasive breast cancer in the tamoxifen group ( 57 cases) than in the raloxifene group ( 80 cases) ( incidence, 1.51 vs 2.11 per 1000; RR, 1.40; 95% CI, 0.98- 2.00). There were 36 cases of uterine cancer with tamoxifen and 23 with raloxifene ( RR, 0.62; 95% CI, 0.35-1.08). No differences were found for other invasive cancer sites, for ischemic heart disease events, or for stroke. Thromboembolic events occurred less often in the raloxifene group ( RR, 0.70; 95% CI, 0.54-0.91). The number of osteoporotic fractures in the groups was similar. There were fewer cataracts ( RR, 0.79; 95% CI, 0.68-0.92) and cataract surgeries ( RR, 0.82; 95% CI, 0.68-0.99) in the women taking raloxifene. There was no difference in the total number of deaths ( 101 vs 96 for tamoxifen vs raloxifene) or in causes of death.Conclusions Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of thromboembolic events and cataracts but a nonstatistically significant higher risk of noninvasive breast cancer. The risk of other cancers, fractures, ischemic heart disease, and stroke is similar for both drugs.