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他莫西芬辅助治疗10年优于5年

Ten Years of Adjuvant Tamoxifen Found Superior to Five
来源:EGMN 2012-12-11 10:30点击:1437发表评论

圣安东尼奥——英国牛津大学的Richard Gray教授在圣安东尼奥乳腺癌研讨会上报告,对于雌激素受体阳性的早期乳腺癌患者,5年他莫西芬辅助治疗已被证明是具有长期后续效应的良好方案,而最新研究显示,10年治疗还要更胜一筹。这项研究结果已同期发表在《柳叶刀》杂志在线版上(Lancet 2012 Dec. 5 [doi: 10.1016/S0140-6736(12)61963-1])。

来自ATLAS(他莫西芬辅助治疗:长短疗程对比)试验的最新分析显示,随机分组接受10年他莫西芬辅助治疗的患者,在诊断后10~14年期间的复发率比治疗5年即停药的患者降低25%,乳腺癌死亡率降低29%。


Richard Gray教授

这一来自ATLAS的结果比2011早期乳腺癌试验者协作组概述分析结果更激动人心。后者纳入了超过10,000例女性患者的15年随访数据,对5年他莫西芬治疗与无他莫西芬治疗进行了对比(Lancet 2011;378:771-84)。这项Meta分析显示,5年他莫西芬治疗可使头5年内的乳腺癌死亡率降低34%,并使接下来5年内的乳腺癌死亡率降低27%。

因此,Gray教授指出,10年他莫西芬治疗必须同5年治疗的明显后续效应竞争。通过将ATLAS和牛津概述的风险下降率相乘,Gray教授估算得出,与无他莫西芬治疗相比,10年他莫西芬治疗可使诊断后头10年内的乳腺癌死亡率下降1/3,接下来10年间的乳腺癌死亡率下降1/2。

获益远超风险

ATLAS 分析涉及6,846名随机的雌激素受体阳性乳腺癌女性患者。10年他莫西芬治疗组患者在诊断后第5~14年间的复发累积风险为21.4%,而对照组(治疗5年后停药)为25.1%,在次期间的乳腺癌死亡率分别为12.2%和15.0%。

Gray 教授指出,10年他莫西芬治疗相比5年治疗的获益远远超出风险。10年他莫西芬治疗组患者在诊断后第5~14年间的子宫内膜癌累积风险为3.1%,对照组为1.6%,子宫内膜癌死亡率分别为0.4%和0.2%。“我认为ATLAS的上述结果与很大范围的女性有关。这些发现使我们想到,芳香酶抑制剂或许也能通过延长疗程而提高疗效。”

事实上,已经有多项临床试验正在对10年芳香酶抑制剂辅助治疗与5年治疗进行对比。但是,芳香酶抑制剂不适用于绝经前女性患者。而且,部分绝经后乳腺癌患者无法耐受芳香酶抑制剂的关节痛、骨痛等副作用。尽管芳香酶抑制剂目前是美国和欧洲对于绝经后患者的标准辅助治疗药物,但发展中国家仍在广泛使用他莫西芬,因为后者价格远远低于芳香酶抑制剂。

诱人的数据

德克萨斯大学癌症治疗与研究中心的Peter Ravdin博士认为ATLAS的数据非常诱人。“我认为这项试验的结果很快就会对绝经前女性产生重要影响。对于正在接受他莫西芬治疗的患者,我们此前一直是让她们在治疗5年后停药。然而今后,我们或许应当告诉她们,已经有临床证据显示10年治疗比5年治疗更好。”

远期复发风险相对较高的女性(肿瘤较大和/或淋巴结阳性)明显适宜接受持续治疗。而对于较小的1级肿瘤和早期、远期复发风险均很低的女性,假如她们不愿使用他莫西芬超过5年,那么就需要谨慎决定了。

绝经前患者的他莫西芬相关子宫内膜癌风险微不足道。但是他莫西芬诱导性面部潮红或阴道症状可能会使部分患者不愿在5年治疗后继续使用他莫西芬。

ATLAS试验由英国癌症研究所、英国医学研究委员会、阿斯利康、美国陆军和EU Biomed资助。Gray教授报告称无相关利益冲突。

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By: BRUCE JANCIN, Oncology Practice

SAN ANTONIO – Five years of adjuvant tamoxifen in women with estrogen receptor–positive early breast cancer is well established as being excellent therapy with a long-term carryover effect. Now 10 years has been shown to be even better.

A new analysis from the large international ATLAS trial demonstrated that participants randomized to 10 years of adjuvant tamoxifen had a 25% reduction in recurrences and a 29% lower mortality due to breast cancer in years 10-14 after diagnosis, compared with women who stopped the drug after the standard 5 years, Richard Gray, M.Sc., reported at the San Antonio Breast Cancer Symposium.

These findings from ATLAS (Adjuvant Tamoxifen: Longer Against Shorter) are all the more impressive in light of the 2011 Early Breast Cancer Trialists’ Collaborative Group overview analysis, which features 15 years of follow-up of more than 10,000 women in randomized trials pitting 5 years of tamoxifen versus no tamoxifen (Lancet 2011;378:771-84). The meta-analysis showed that 5 years of tamoxifen reduced deaths due to breast cancer by 34% during the first 5 years after treatment ended and by 27% in the subsequent 5 years.

Thus, 10 years of tamoxifen had to compete against a big carryover effect of 5 years of the drug, noted Mr. Gray, professor of medical statistics at the University of Oxford (U.K.).

By multiplying the risk reduction ratios from ATLAS and the Oxford overview, he estimated that 10 years of tamoxifen reduces breast cancer mortality by one-third in the first decade following diagnosis and by fully half in the second decade, compared with no tamoxifen.

Benefits Far Outweigh Risks

The ATLAS analysis involved 6,846 randomized women with estrogen receptor–positive disease. The cumulative risk of recurrence during years 5-14 after diagnosis was 21.4% in women assigned to 10 years of tamoxifen and 25.1% in controls. Breast cancer mortality during years 5-14 was 12.2% in patients on 10 years of tamoxifen and 15.0% in those who stopped after 5 years, for an absolute mortality reduction of 2.8%.

The benefits of 10 years of tamoxifen compared with 5 far outweighed the risks, Prof. Gray continued. The cumulative risk of endometrial cancer in years 5-14 was 3.1% for women randomized to continue therapy for 10 years, compared with 1.6% for controls. Mortality due to endometrial cancer was rare, however: 0.4% in the extended therapy group and 0.2% in controls.

"I think these ATLAS results are relevant to quite a wide range of women. And the findings encourage one to think that aromatase inhibitors, too, might be more effective with longer therapy," he said.

Indeed, ongoing clinical trials are comparing outcomes with 10 versus the standard 5 years of adjuvant aromatase inhibitor therapy.

But aromatase inhibitors are not an option in premenopausal patients because they’re ineffective in that setting. In addition, some postmenopausal breast cancer patients can’t tolerate aromatase inhibitors due to arthralgias, bone pain, or other side effects. And while aromatase inhibitors are now the standard of care for adjuvant therapy in postmenopausal patients in the United States and Europe, tamoxifen remains widely used in developing countries because it’s so much less expensive, he added.

Data Are Compelling

Dr. Peter Ravdin called the ATLAS data compelling.

"I think the results of this trial will have a major immediate impact on premenopausal women. For women who are now approaching 5 years of therapy, up until this point we’d have told them we’re going to be stopping the drug. Now we’re going to be telling them that there’s clinical evidence that 10 years is superior to 5 years. And I’m going to be comfortable doing that," said Dr. Ravdin, director of the breast health clinic at the Cancer Therapy and Research Center of the University of Texas, San Antonio.

"One of the things that I think is profoundly important about this study is that the biology of the disease shows that there are some women fated to have late relapse that our early treatments aren’t effective in blocking, but that we can do better by treating women with hormonal therapy beyond 5 years," he added.

Women with a relatively high risk of late relapse – that is, those with larger tumors and/or positive lymph nodes – will definitely be strong candidates for continuation of therapy. Those with small grade 1 tumors and a very low risk of both early and late relapse might rationally decide they don’t want to take tamoxifen for longer than 5 years, according to the oncologist.

The risk of tamoxifen-related endometrial cancer in premenopausal patients is negligible. But some women experience such problematic tamoxifen-induced hot flashes or vaginal symptoms that they may balk at continuing treatment beyond 5 years.

"I think that the amount of benefit they’ll get in continuing will be small enough that that would be a perfectly rational decision. An additional one-third reduction in a very small risk is still a very small benefit," Dr. Ravdin observed.

Simultaneous with Prof. Gray’s presentation in San Antonio, the ATLAS results were published online (Lancet 2012 Dec. 5 [doi: 10.1016/S0140-6736(12)61963-1]).

The ATLAS trial was funded by Cancer Research UK, the UK Medical Research Council, AstraZeneca, the U.S. Army, and EU Biomed. Dr. Gray reported having no financial conflicts.

学科代码:肿瘤学 妇产科学   关键词:圣安东尼奥乳腺癌研讨会 他莫西芬辅助治疗
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