当前位置 > 首页 > 新闻动态 > 科技前沿
显著降低乳腺癌死亡率的药物
发表日期: 2015-08-11 作者: EBCTCG 文章来源:《The Lancet》
打印 文本大小:    

 

 

最近,在超过30000名女性中开展的一项大型研究表明,一类称为芳香化酶抑制剂的药物,可显著降低最常见乳腺癌类型患病绝经后妇女的死亡风险。这项研究结果,发表在七月二十三日的《柳叶刀》杂志(The Lancet)。

这项研究强调了芳香化酶抑制剂在雌激素受体(ER)阳性乳腺癌治疗中的重要性,并指出,与较旧的激素治疗他莫昔芬相比,它们能够更加显著地降低死亡风险。

这项研究结果,发表在七月二十三日的《柳叶刀》杂志(The Lancet)。在治疗过程中,每一次试验都在不同时期使用了芳香化酶抑制剂和三苯氧胺。延伸阅读:饮食干预助力乳腺癌靶向治疗。

在这项研究中,英国癌症研究所Mitch Dowsett教授带领的研究人员,与牛津大学临床试验服务部门的同事合作,对来自9个临床试验中31,920名妇女的结果进行了综合分析。

芳香化酶抑制剂可抑制雌激素的合成。以前有报道称,它们可比他莫昔芬更有效地降低乳腺癌复发风险,但是,它们是否能改善生存率,并没有得到证实。

目前的研究表明,与无激素治疗相比,连续5年服用芳香化酶抑制剂,可使ER阳性乳腺癌绝经后妇女死于该病的风险降低40%。通过5年服用他莫昔芬,则降低了30%

目前的临床指南反映了“在治疗过程中何时使用芳香化酶抑制剂或他莫昔芬”的不确定性,但是新的研究有助于阐明这些建议。

本研究第一作者Mitch Dowsett教授说:“我们这项全球合作研究表明,通过服用芳香化酶抑制剂5年的时间,绝经后妇女死于最常见形式乳腺癌的风险降低了40%,保护作用显著比他莫昔芬强。芳香化酶抑制剂消除只除去少量雌激素——它们在绝经后仍然停留在女性血液循环中,但那足以对各种ER阳性肿瘤产生重大的影响,尽管这些肿瘤在分子水平上具有独特的差异。但是,芳香化酶抑制剂治疗并不会摆脱副作用,重要的是,要确保有显著副作用的妇女,能够被支持尝试继续采取治疗,并充分受益于它。”

癌症研究所首席执行官Paul Workman教授说:“有关芳香化酶抑制剂的证据已经积累了超过十年,但是要弄清所有的数据,并为临床指南提供一个坚实的基础,需要进行这种庞大而复杂的研究。通常是,发现新的治疗方法占据着头条新闻,但是,最大限度地提高患者从现有治疗方法所获得的益处,也是同样重要的。”

The Royal Marsden乳腺部门主任Ian Smith教授说:“The Royal Marsden特别高兴看到妇女乳腺癌的这个重要进步,因为我们是参与发展来曲唑(最有效的芳香化酶抑制剂之一)的主要机构。这种药物现在已被世界各地广泛应用,令人欣慰的是,多年来已经有许多生命得到了挽救。”

这项与另一项关于不同药物类型(二膦盐酸)的乳腺癌研究(由牛津大学和谢菲尔德大学完成),共同发表在同一期的《The Lancet》。英国癌症研究中心的高级科学信息经理Nell Barrie针对这两项研究发表评论说:“这两项研究提供了进一步的证据表明,芳香化酶抑制剂和二膦酸盐类药物——都是目前可用的治疗方法,可帮助更年期妇女预防乳腺癌。”

“二膦酸盐有助于保持骨骼健康,这些结果表明,它们可减少绝经后妇女乳腺癌复发到骨骼的几率。芳香化酶抑制剂能阻断人体制造雌激素的能力,雌激素能刺激乳腺癌的生长,这些结果证实,它们可以帮助阻止疾病在治疗后复发。”

英国癌症研究所(ICR)和The Royal Marsden,在早期以及目前的临床试验中发挥了主导作用,结果表明了芳香化酶抑制剂在乳腺癌中的有效性。这些研究支持NICE的建议:这些药物应该是某些女性在手术后的首要激素治疗。(来源:生物通  王英)

 

Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials

 

Abstract  Background  The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain.

Methods  We undertook meta-analyses of individual data on 31920 postmenopausal women with oestrogen-receptor-positive early breast cancer in the randomised trials of 5 years of aromatase inhibitor versus 5 years of tamoxifen; of 5 years of aromatase inhibitor versus 2–3 years of tamoxifen then aromatase inhibitor to year 5; and of 2–3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen. Primary outcomes were any recurrence of breast cancer, breast cancer mortality, death without recurrence, and all-cause mortality. Intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded aromatase inhibitor versus tamoxifen first-event rate ratios (RRs).

Findings  In the comparison of 5 years of aromatase inhibitor versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 0–1 (RR 0·64, 95% CI 0·52–0·78) and 2–4 (RR 0·80, 0·68–0·93), and non-significantly thereafter. 10-year breast cancer mortality was lower with aromatase inhibitors than tamoxifen (12·1% vs 14·2%; RR 0·85, 0·75–0·96; 2p=0·009). In the comparison of 5 years of aromatase inhibitor versus 2–3 years of tamoxifen then aromatase inhibitor to year 5, recurrence RRs favoured aromatase inhibitors significantly during years 0–1 (RR 0·74, 0·62–0·89) but not while both groups received aromatase inhibitors during years 2–4, or thereafter; overall in these trials, there were fewer recurrences with 5 years of aromatase inhibitors than with tamoxifen then aromatase inhibitors (RR 0·90, 0·81–0·99; 2p=0·045), though the breast cancer mortality reduction was not significant (RR 0·89, 0·78–1·03; 2p=0·11). In the comparison of 2–3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 2–4 (RR 0·56, 0·46–0·67) but not subsequently, and 10-year breast cancer mortality was lower with switching to aromatase inhibitors than with remaining on tamoxifen (8·7% vs 10·1%; 2p=0·015). Aggregating all three types of comparison, recurrence RRs favoured aromatase inhibitors during periods when treatments differed (RR 0·70, 0·64–0·77), but not significantly thereafter (RR 0·93, 0·86–1·01; 2p=0·08). Breast cancer mortality was reduced both while treatments differed (RR 0·79, 0·67–0·92), and subsequently (RR 0·89, 0·81–0·99), and for all periods combined (RR 0·86, 0·80–0·94; 2p=0·0005). All-cause mortality was also reduced (RR 0·88, 0·82–0·94; 2p=0·0003). RRs differed little by age, body-mass index, stage, grade, progesterone receptor status, or HER2 status. There were fewer endometrial cancers with aromatase inhibitors than tamoxifen (10-year incidence 0·4% vs 1·2%; RR 0·33, 0·21–0·51) but more bone fractures (5-year risk 8·2% vs 5·5%; RR 1·42, 1·28–1·57); non-breast-cancer mortality was similar.

 

原文链接:http://ac.els-cdn.com/S0140673615610741/1-s2.0-S0140673615610741-main.pdf?_tid=5b89f2f4-33fa-11e5-9593-00000aacb361&acdnat=1437958787_ea945f71421b2da515f32a270316155a

 


电话:028-82890289   传真:028-82890288   Email:swsb@cib.ac.cn
邮政编码:610213   地址:四川省成都市天府新区群贤南街23号
中国科学院成都生物研究所 版权所有
蜀ICP备05005370号-1