Oncology Frontier: For HER2-positive breast cancer， anti-HER2 therapy should be included in the neo-adjuvant therapy. We know the standard duration of trastuzumab is one year in adjuvant therapy. But what is the optimal strategy and duration of trastuzumab in neo-adjuvant therapy?

　　《肿瘤瞭望》：对于HER2阳性乳腺癌，抗HER2治疗应纳入新辅助治疗。我们知道，曲妥珠单抗在辅助治疗中的标准用药时间为一年。那么，在新辅助治疗中，曲妥珠单抗的最佳策略和用药时间是什么？

　　Prof Hudis: The issue of the appropriate anti-HER2 therapy for the neoadjuvant setting in extremely controversial right now， at least in the United States where pertuzumab has been approved in exactly that setting. We give systemic therapy in the early stage setting to cure people. If we stop at that thought， then that indicates to me that whatever duration you give in the pre-op setting， overall you should end up giving the exact same treatment as you would in the adjuvant patient. If one year of trastuzumab is the standard therapy in the adjuvant setting， then any patient who begins trastuzumab in the pre-op setting ought to be planning to get it for that same full year， even if some of that treatment is given after surgery. I will add something to that which is provocative. For me， the pertuzumab approval in the US， which is for 4-6 months of use in the pre-op setting， may be inadequate. It was given accelerated approval and the confirmatory data will come from APHINITY which plans for a full year of pertuzumab added to a full year of trastuzumab. If APHINITY is positive， then it is not going to be clear to me that giving 4-6 months of pertuzumab and stopping will have been of much benefit to patients. I’ve spoken on this topic for a while now and my point of view is that you give the same in the pre-op setting as you do in the post-op setting because your ultimate aim is to cure the patient’s systemic disease.

　　Hudis教授：当前，适当的抗HER-2治疗在新辅助治疗中是极具争议的问题，至少在美国是这样，因为帕妥珠单抗作为新辅助治疗用药已在美国得到了批准。我们在早期治疗阶段给予全身治疗来治愈患者。如果我们停留在这个想法，那么我认为这意味着，无论术前给予了多长时间的治疗，总不该影响到辅助治疗原本应给予患者的治疗。如果曲妥珠单抗在辅助治疗中的标准用药时间为1年，那么在术前开始使用曲妥珠单抗的任何患者都应计划用药满1年，即使部分用药是在术后进行。我要补充说明，这可能会引起一些人反对。对我来说，美国批准帕妥珠单抗术前用药4~6个月，这可能是不适当的。它被赋予加速审批，而验证性数据将来自APHINITY试验，后者计划在曲妥珠单抗1年用药期上加入帕妥珠单抗1年用药期。如果APHINITY试验结果是肯定的，那么给予4~6个月帕妥珠单抗后停止给药会给患者更大获益，我怀疑这一点。对这个话题我已经发表了意见，而现在我的观点是，术前给药应与术后给药的方案相同，因为我们的最终目的是治愈患者的全身性疾病。

　　Oncology Frontier: Obesity is related to the risk of many types of cancer， including breast cancer. More and more studies show that the negative effect of obesity is far more than increasing the risk of disease. Could you please summarize the hazards of obesity and the possible underlying mechanism?

　　《肿瘤瞭望》：肥胖与包括乳腺癌在内的许多类型癌症的风险相关。越来越多的研究表明，肥胖的负面影响远不止是增加心脏病的风险。能否请您总结一下肥胖的危害及背后可能的机制？

　　Prof Hudis: Obesity is actually on the path to replacing tobacco as the leading modifiable risk factor in the United States. As a reminder， a non-modifiable risk factor like age is something we can’t do anything about， but a modifiable risk factor we can. Now that we have done a better job of controlling tobacco use and abuse， we are being confronted with the problem of obesity. Obesity itself is increasing in incidence in almost all Western countries， in fact， globally. It will probably replace tobacco as the leading modifiable risk factor for many of the solid tumors that are part of our regular practice. This is especially true for endometrial cancer， but it is also true for breast cancer. In a very simple way， we have been able to uncover a link between obesity and the low-grade chronic subcutaneous inflammation in fat and other tissues， and the generation of active molecules that turn on the CYP19 gene which is the gene that codes aromatase. If this happens as described， it would be expected that there would be elevated levels of estradiol in the tissues of obese versus lean people. To some degree， we have seen this play out now in both animal models and in people.

　　Hudis教授：事实上，肥胖正在逐渐取代烟草成为美国头等可改变的危险因素。需要提醒的是，对诸如年龄等这些不可改变的危险因素，我们无计可施，但可改变的危险因素则不同。现在，我们在控制烟草的使用和滥用上已经有所成效，如今正面临着肥胖问题。在几乎所有西方国家，肥胖本身的发病率正在增加，事实上，在全球范围也是如此。它很可能将取代烟草成为我们日常工作中所接触的许多实体瘤的头等可改变的危险因素。对子宫内膜癌尤其如此，但也适用于乳腺癌。通过一个非常简单的方法，我们已经能够发现肥胖与脂肪和其他组织中低度慢性皮下炎症之间的联系，以及肥胖与活性分子的产生之间的联系，后者可开启用于编码芳香化酶的基因CYP19。如果真的是所描述的这种情况，我们可以预计，胖者比瘦者组织中的雌二醇水平更高。如今，这一点在某种程度上已在动物模型和人体中得到了印证。

　　Oncology Frontier: In an evidence-based era， a prospective， randomized， controlled trial， or better， double-blind and large sample， can provide the most robust evidence. However， in your lecture， you questioned its role in the era of big data. Why? And what should we do to get up to date?

　　《肿瘤瞭望》：在循证医学的时代，前瞻性随机对照试验，特别是双盲和大样本的试验可以提供最有力的证据。然而，在您的演讲中，您质疑了它在大数据时代中的作用。为什么呢？我们应该怎样做才能获取最新信息呢？

　　Prof Hudis: The randomized clinical trial is the gold standard for the generation of evidence but it has limits. The types of patients that are accrued do not necessarily reflect those we see and treat in the real world. They are expensive and time-consuming to conduct. And we don’t have the resources to ask randomized questions about every single issue that comes up. The promise of big data is that it will allow us to fill in some of those gaps， extending observations from randomized clinical trials and， in fact， enabling us to do more efficient focused clinical trials sometimes. So it is not that it is an either/or choice; it is that they are complementary， one to the other.

　　Hudis教授：随机临床试验是产生证据的金标准，但它也有其局限性。试验中的患者类型并不一定反映我们在现实中治疗和观察到的类型。试验的开展耗费大量资金和时间。我们没有足够的资源来针对所出现的每一个问题进行随机提问。大数据的前景是，它将使我们能够填补其中的一些空白，扩展从随机临床试验中的观察，事实上，它有时还能使我们进行更加高效有针对性的临床试验。所以这不是一个非此即彼的选择，而是说它们之间是互补的。

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

　　《肿瘤瞭望》：专家组在星期六将讨论并投票达成圣加仑国际共识。在您看来，今年圣加仑共识最重要的更新将是什么？

　　Prof Hudis: I actually don’t know what the most important update will be. The thing about the St Gallen consensus is that we really run the whole range of local to systemic therapies and I think it depends on what you think is important. I am optimistic that we will come together and look at this wide range of data across the broad spectrum of clinical trials and clinical decisions that we make and reach consensus. One thing I have to point out is that these St Gallen conferences are influential; many people around the world rely on them. It is really an honor to take part in this meeting.

　　Hudis教授：事实上我并不知道最重要的更新会是什么。就我所知，圣加仑共识确实涉及局部治疗到全身治疗的整个范围，我认为重要性取决于个人的想法。我乐观地认为，我们聚到一起，共同查看这些广泛遍布于临床试验和临床决策的大范围数据，制定并达成共识。我要指出的一点是，这些圣加仑会议是有影响力的，得到世界各地许多人的信赖。能够参与本次会议我真的感到非常荣幸。