专家简介：Eric P. Winer，  MD， FASCO，美国Dana-Farber癌症研究所乳腺癌研究Thompson高级研究员、妇女癌症部部长、乳腺肿瘤中心主任，哈佛医学院医学教授。圣加仑早期乳腺癌专家共识专家组主席、ASCO指导委员会成员、乳腺癌咨询专家组成员、临床实践指南委员会成员、领导力发展工作组成员、乳腺癌指南建议小组成员。Winer教授的研究组主要致力于通过临床试验开发新药和新治疗方案，提高和改善乳腺癌患者的管理和生活质量。Winer教授同时也是肿瘤学临床试验联盟乳腺癌委员会的联席主席。

访谈原文

　　Oncology Frontier: Multi-gene molecular assays can provide accurate and reproducible prognostic information， and sometimes predict the response to chemotherapy. However， they are too expensive and depend highly on the techniques. So in the area where multi-gene molecular assays are unavailable， what’s the indication for chemotherapy in patients with luminal A-like type breast cancer?

 　　《肿瘤瞭望》：多基因分子检测方法能提供精确和可重复的预后信息，能预测对化疗的反应性。但是，其花费太高，并且有很高的技术要求。那么，在多基因分子检测方法不可用的区域，Luminal A样乳腺癌患者的化疗适应证是什么？

　　Dr Winer: I don’t think the answer is to just give everyone chemotherapy. If you have a patient who has an estrogen and progesterone receptor-positive cancer that is not a high-grade cancer (i.e. a low to intermediate grade cancer)， I personally think that it is reasonable to have a conversation with the patient about endocrine therapy alone， assuming she doesn’t have stage III breast cancer. For the patient who has lymph node-negative breast cancer and even selectively for the patient who has one to three positive lymph nodes， it is not unreasonable to think about omitting chemotherapy. However， the more disease a woman has， the more uncomfortable I become at omitting it without further information from one of the multi-gene assays. Personally， I am not a fan of Ki-67. My own sense of this is that the testing is quite variable and unreliable and I don’t think it is something we can necessarily substitute for a multi-gene assay.

 　　Winer教授：我不认为需要对每一位患者都进行化疗。如果你遇到这样一位患者，她的雌激素受体和孕激素受体阳性、肿瘤级别不高（即低到中级），我个人认为如果不是III期乳腺癌，建议她仅用内分泌治疗是合理的。对于淋巴结阴性的乳腺癌患者，甚至有1~3个淋巴结阳性的乳腺癌患者，考虑不进行化疗也不是不合理的。然而，患者的疾病负担越重，在没有通过多基因检测获得更多信息的情况下，不给予化疗我就越不踏实。我个人并不是Ki-67的推崇者。我自己的感觉是，这个指标的变数相当大，并不可靠，我并不认为它可以可靠地代替多基因检测。

　　Oncology Frontier:  Which chemotherapy strategies would you suggest for selected patients with luminal A-like type breast cancer?

 　　《肿瘤瞭望》：您建议特定Luminal A样乳腺癌患者选择什么样的化疗方案？

　　Dr Winer:The situation with luminal A-like breast cancer is that the tumors tend not to be terribly chemotherapy responsive. If you are using chemotherapy， you are using it because the patient has a particularly high disease burden and you are trying to not leave any stone unturned in terms of reducing the risk of disease recurrence. In that context， you can use any chemotherapy regimen although in our own institution， the fact is that if we had someone with stage III luminal A-like breast cancer who did not have a strong preference not to receive chemotherapy then we would treat her with chemotherapy and not obtain a multi-gene assay in that setting of stage III disease， and most of the time， we would probably treat her with an anthracycline followed by a taxane.

 　　Winer教授：Luminal A 样乳腺癌的情况是，肿瘤对化疗的应答往往并不强。如果使用化疗，是因为患者有特别高的疾病负担，你千方百计不想错失任何可以减少疾病复发风险的机会而使用化疗。在这种情况下，你可以使用任何化疗方案。我们研究所的情况是，如果有一位Ⅲ期Luminal A样乳腺癌患者，患者本人并不是强烈拒绝化疗，我们就会在未进行多基因检测的情况下，对其实施化疗。而且大多数时候，我们可能会选择蒽环序贯紫杉的方案。

　　Oncology Frontier: A growing number of studies indicate that to treat different types of patient， different strategies should be taken. That’s called tailoring therapy. For example， there are some investigations on fewer drugs in combination and shorter duration of chemotherapy， like the NSABP-B studies， which got a comparable result with traditional strategy. So the question is， do we really need so many drug combinations and such intensive therapy? What kinds of patients should be considered for such therapy?

 　　《肿瘤瞭望》：越来越多的研究表明，治疗不同类型的患者，应采取不同的治疗方案。这就是所谓的个体化疗法。例如，有一些研究关于联合更少的药物和更短的时间进行化疗，像NSABP-B的研究，与传统治疗方案进行了比较。我们真的需要这么多的药物联合和高强度的治疗吗？什么样的患者可以考虑这种治疗？

　　Dr Winer:The NSABP B30 study actually demonstrated that AC followed by paclitaxel was better than four cycles of an anthracycline and docetaxel， so it’s a little hard to know which regimens can be used that are tailored for the individual tumor. I do believe that patients who have a lower disease burden and stage I disease， for example， in general don’t need such an extensive chemotherapy regimen. The benefits of the treatment are smaller. The risks of the regimen don’t change because the benefits are smaller. So if I am going to use chemotherapy， I am going to use a better-tolerated regimen. The one situation where we have a fair degree of confidence that we can back away from some of the traditional chemotherapies is in patients with stage I HER2-positive cancers， where we have demonstrated that giving twelve weeks of paclitaxel with a year of trastuzumab gives extraordinary outcomes at least in the relatively short term.

 　　Winer教授：NSABP-B30研究的结果实际上表明，AC方案联合紫杉醇的疗效优于4个周期的蒽环联合多西他赛，所以要知道哪个方案可以个体化地应用于某个个体肿瘤可以有些困难。我相信，疾病负担较低的患者，例如Ⅰ期乳腺癌患者，一般不需要强度如此之大的化疗。治疗的益处较小，正因如此，其风险也没什么改变。所以，如果是我，我会选择耐受性更好的化疗方案。不过有一种情况，我们有相当的信心认为可以放弃传统的化疗方案，这种情况即Ⅰ期、HER-2阳性乳腺癌。已经证明，对这类患者给予12周紫杉醇与1年曲妥珠单抗治疗——至少在短期内——可取得非凡的治疗效果。

　　Oncology Frontier: There is no optimal adjunctive chemotherapy for triple-negative breast (TNB) cancer for now. Will you agree that platinum-based therapy should be used in triple-negative breast cancer， at least in some certain situation and in some certain patients?

 　　《肿瘤瞭望》：现在，三阴性乳腺癌（TNBC）没有最优辅助化疗方案。您是否同意，至少在某些特定情况或某些特定的TNBC患者中，应该使用以铂类为基础的治疗？

　　Dr Winer:As a general rule， platinum shouldn’t be used as an adjuvant therapy for triple-negative breast cancer. The one exception I would give to that is the patient who has a BRCA mutation. In that context， I think we are in a place where we have enough data where one can make the choice to use platinum that is based on pretty solid evidence although not direct evidence. For all other patients with triple-negative breast cancer， we know there is an improvement in pathologic complete response but we do not know that that leads to an improvement in disease-free or overall survival. Until we have those data， I would not encourage the use of platinum in that setting.

 　　Winer教授：一般原则是，铂类不应该被用作TNBC的辅助治疗。使用铂类药物的一个例外是BRCA基因突变的TNBC患者。在这方面，我想我们有足够的数据，支持选择使用铂类是基于相当确凿的证据，虽然没有直接证据。对于所有其他TNBC患者，我们知道在铂类可使病理完全缓解率有改善，但我们不知道，这是否能导致无病生存或总体生存的改善。在掌握这些数据前，我不鼓励使用铂类。

　　Oncology Frontier: On Saturday， the expert panel will discuss and vote for the St. Gallen international consensus. From your perspective， what will be the most important update in the St. Gallen consensus this year?

 　　《肿瘤瞭望》：在您看来，今年圣加仑共识最重要的更新是什么？

　　Dr Winer:I think there are a few updates that will be important. The panel will certainly consider more comprehensively than in the past， the role of ovarian suppression and the role of aromatase inhibitors in premenopausal women. That may be the most far-reaching and important area that the panel chooses to tackle. There will be discussion about anti-HER2 regimens in the adjuvant setting. I don’t think anything has changed too dramatically in the setting of triple-negative breast cancer that will have much impact. Finally， I think there will be some discussion about certain local therapy issues and discussions about acceptable margins. It was raised yesterday that we should begin to think of very low estrogen-positivity as the equivalent of triple-negative disease and whether or not that gets into the discussion remains to be seen， but it is certainly an interesting question.

　　Winer教授：我认为将有一些很重要的更新。专家小组对卵巢抑制和芳香化酶抑制剂在绝经前乳腺癌中的作用将会进行更全面的思考。这可能是专家小组决定解决的最深远和最重要的领域。共识中将会有关于辅助治疗中抗HER-2治疗方案的讨论。在三阴性乳腺癌方面我认为没有什么可能产生很大影响的显著变化。最后，我认为会有关于某些局部治疗问题和可接受切缘的讨论。3月20日会上有专家提出，像对待三阴性乳腺癌一样，我们也应该考虑定义极低雌激素水平乳腺癌，这一问题是否该进入讨论还有待观察，但肯定是一个有趣的问题。

　　Oncology Frontier: Tailoring therapy and precision treatment are keywords at St. Gallen 2015. Do you think age is an important factor to design an individualized treatment strategy? What are the key factors that should be considered for very young women and very old women， respectively?

 　　《肿瘤瞭望》：个体化治疗和精准治疗是圣加仑共识2015年的关键词，您认为年龄是设计个性化治疗方案的重要因素吗？对于非常年轻的妇女和老年妇女，应该考虑的关键因素分别是什么？

　　Dr Winer:Age is important， although we have to be careful not to discriminate against older women and make appropriate decisions keeping age in mind. And we have to be careful not to discriminate against younger women in that we tend to over-treat young women if anything. With older women， we have to remember two things. First， there are competing causes of mortality and some of the women who receive treatment will simply not live long enough to see the benefits of that therapy. The second consideration is that they typically have more significant toxicity. If you treat a 75 or 80 year old woman with a course of adjuvant chemotherapy， there is probably no better way than that to make her feel like she is 80 or 85. To what extent that impacts on her negatively in terms of long-term health is less than fully clear. In young women， I think we need to get away from the assumption that all breast cancer in young women is associated with a poor prognosis. While the distribution of tumors in younger women is different than in older women and tend， on average， to be more aggressive tumors， there are cancers in young women that are luminal A-like that are probably best treated with hormonal therapy alone.

　　Winer教授：年龄是很重要，但我们必须谨慎，不要特别对待老年患者，要结合年龄做出恰当的决定。我们也必须谨慎，不要特别对待年轻患者，否则可能倾向于过度治疗。

　　对于老年妇女，我们要记住两点。首先是死亡的竞争原因，一些接受治疗的患者根本活不到从治疗中获益的那一天。第二点是药物通常会对她们产生更显著的毒性。如果你用哪怕一个疗程的辅助化疗治疗1名75岁或80岁的患者，你会发现这是最有效的使患者觉得自己是80岁或85岁的方法。这对患者的长期健康能产生多大程度的负面影响，还不完全清楚。

　　对于年轻女性，我认为我们需要摆脱所有年轻乳腺癌患者都预后不良的假设。虽然肿瘤的分布在年轻女性中与在年龄较大的女性中不同，通常而言，在年轻妇女中是更具侵袭性，但也有一些年轻的Luminal A样乳腺癌患者可能可仅接受激素疗法。