Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial.
Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial.
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DOI：
10.1016/s1470-2045(14)71171-4
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发表时间：
2015-01
期刊：
影响因子：
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通讯作者：
IBIS-I Investigators
中科院分区：
文献类型：
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作者：
Cuzick J;Sestak I;Cawthorn S;Hamed H;Holli K;Howell A;Forbes JF;IBIS-I Investigators
之前发表的四项随机临床试验表明，在最初10年的随访中，他莫昔芬可以降低患乳腺癌风险增加的健康女性的乳腺癌风险。我们报道了IBIS-I试验的长期随访，在该试验中，参与者和研究人员在很大程度上仍然没有接受治疗分配。在IBIS-I随机对照试验中，35-70岁被认为有患乳腺癌风险增加的绝经前和绝经后妇女被随机分配(1：1)，每天服用他莫昔芬20毫克或服用匹配的安慰剂，为期5年。患者通过电话或传真被随机分配到两个治疗组，按照区组随机化计划(排列后的区组大小为6或10)。患者和研究人员通过使用中心随机化和编码药物供应来掩饰治疗分配。主要终点是乳腺癌(浸润性乳腺癌和导管原位癌)的发生，按治疗意图进行分析。使用COX比例风险模型评估乳腺癌的发生和死亡率。该试验已停止招募，积极治疗已完成，但长期随访仍在进行中。这项试验在Controledtrials.com注册，编号为ISRCTN91879928。在1992年4月14日至2001年3月30日期间，从8个国家和地区的遗传学诊所和乳房护理诊所招募的7154名符合条件的妇女参加了IBIS-I试验，并被随机分配到两个治疗组：3579人服用他莫昔芬，3575人服用安慰剂。经过平均16.0年(IQR14.1-17.6)的随访，已报告了601例乳腺癌(他莫昔芬组3579名患者251例[7.0%]，安慰剂组3575名女性350例[9.8%]；风险比[HR]0.71[95%可信区间0.60-0.83]，p<；0.0001)。发生乳腺癌的风险在0-10年间相似(安慰剂组3575名女性中226[6.3%]对他莫昔芬组3579名女性163[4.6%]；风险比[HR]0.72[95%可信区间0·59-0.88]，p=0.001)和10年后(3295名女性分别为124[3.8%]对3343名88[2.6%]；HR 0·69[0.53-0.91]，p=0.009)。浸润性雌激素受体阳性乳腺癌(HR 0·66[95%CI 0·54-0·81]，p<；0·0001)和导管原位癌(0·65[0·43-1·00]，p=0·05)风险降低最大，而浸润性雌激素受体阴性乳腺癌(HR 1·05[95%CI 0·71-1·57]，p=0·8)风险降低最大。这些结果表明，他莫昔芬在治疗停止后提供了非常长的保护期，从而大大提高了该药物预防乳腺癌的益害比。英国癌症研究中心(UK)和澳大利亚国家健康与医学研究委员会(National Health And Medical Research Council)。
Four previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation. In the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35–70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928. Between April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16·0 years (IQR 14·1–17·6), 601 breast cancers have been reported (251 [7·0%] in 3579 patients in the tamoxifen group vs 350 [9·8%] in 3575 women in the placebo group; hazard ratio [HR] 0·71 [95% CI 0·60–0·83], p<0·0001). The risk of developing breast cancer was similar between years 0–10 (226 [6·3%] in 3575 women in the placebo group vs 163 [4·6%] in 3579 women in the tamoxifen group; hazard ratio [HR] 0·72 [95% CI 0·59–0·88], p=0·001) and after 10 years (124 [3·8%] in 3295 women vs 88 [2·6%] in 3343, respectively; HR 0·69 [0·53–0·91], p=0·009). The greatest reduction in risk was seen in invasive oestrogen receptor-positive breast cancer (HR 0·66 [95% CI 0·54–0·81], p<0·0001) and ductal carcinoma in situ (0·65 [0·43–1·00], p=0·05), but no effect was noted for invasive oestrogen receptor-negative breast cancer (HR 1·05 [95% CI 0·71–1·57], p=0·8). These results show that tamoxifen offers a very long period of protection after treatment cessation, and thus substantially improves the benefit-to-harm ratio of the drug for breast cancer prevention. Cancer Research UK (UK) and the National Health and Medical Research Council (Australia).