F. Cardoso教授 肿瘤及乳腺单位欧洲学校，查帕里玛德癌症中心

　　Oncology Frontier: You have been involved in developing the guidelines for breast cancer treatment. What are the new features of the guidelines?

　　《肿瘤瞭望》：您参与制定了晚期乳腺癌共识，这些共识有哪些新的特色吗？

　　Dr Cardoso: The ESMO Guidelines Committee has updated several guidelines. One of the guidelines updated was the advanced breast cancer guidelines. These guidelines are a joint effort between the European School of Oncology and the European Society of Medical Oncology. They come from a consensus meeting that took place in November last year called the ABC (Advanced Breast Cancer) Consensus Meeting which was an update on what happened two years ago. These are guidelines dedicated to metastatic breast cancer patients who have been forgotten for a long time with the focus being on the early setting. There has been an update of the first guidelines speaking about how to manage the three main subgroups of metastatic breast cancer – triple-negative， HER2-positive (where there are new drugs coming on to the market) and also ER-positive disease. We also devote a significant amount of the guidelines to the management of locally advanced breast cancer. This is a clinical situation where the disease is quite advanced locally and not operable but still doesn’t have distant metastases. This incidence of this type of breast cancer reaches 50-60% in some developing countries whilst in the more Westernized countries， it occurs at 15-20%. There are no specific or dedicated guidelines on how to manage those patients and this was one of the future directions for these guidelines.

　　Cardoso教授：ESMO指南委员会 （the ESMO Guidelines Committee）已经更新了一系列指南，其中一些是晚期乳腺癌的治疗指南。这些指南是欧洲肿瘤学会(the European School of Oncology)和欧洲肿瘤内科学会(the European Society of Medical Oncology)共同努力的结果。它们出自于去年11月份举行的晚期乳腺癌国际共识会议(Advanced Breast Cancer Consensus Meeting)，是基于两年前的指南基础上的更新。在此之前，临床及学术界更关注早期乳腺癌的相关诊治，这项指南重新强化了被遗忘多时的转移性乳腺癌患者的治疗。本次指南更新了转移性乳腺癌三个主要亚型，包括三阴性乳腺癌、HER-2阳性乳腺癌（目前正有新药陆续问世）以及ER阳性乳腺癌的治疗原则。

　　本次指南更新还特别关注了局部晚期乳腺癌(locally advanced breast cancer)的治疗。这是一类局部进展迅速、无法切除、但尚未出现远处转移的乳腺癌。在一些发展中国家，该型乳腺癌的发病率可达50%~60%，而在西方发达国家，其发病率为15%~20%。目前我们尚无详尽的专门针对该类患者的治疗指南，这是治疗指南制定未来发展的方向之一。

　　Oncology Frontier: Is the difference between the rates in developed and developing countries a question of early detection?

　　《肿瘤瞭望》：发达国家和发展中国家发病率的差异，是由早期发现的差异所导致的吗？

　　Dr Cardoso: For this problem specifically yes. Usually in countries where there are no screening programs and no widespread education about the importance of early diagnosis， the cancers are diagnosed later and where the breast cancers are very advanced with distant metastases and/or have become inoperable. That completely changes the prognosis from being a potentially curable disease to a disease with a very bad prognosis， or in the case of metastatic disease， an incurable condition.

　　Cardoso教授：对这一具体问题的答案是“是”。通常在没有筛查、没有普及早期诊断重要性的国家，该类疾病往往诊断较晚。患者常常发展至晚期并伴有远处转移，或者已经失去手术切除机会。这从本质上将一个尚可治愈的疾病转变成一个预后极差的疾病，或者在转移患者中转变成为不可治愈的疾病。

　　Oncology Frontier: What new strategies are available where detection occurs early and the condition is curable?

　　《肿瘤瞭望》：在早期发现和尚可治愈的乳腺癌里，有什么治疗方案呢？

　　Dr Cardoso: These guidelines focus on patients who have advanced disease and fortunately， these patients have a large number of drugs that can be used to treat them in terms of chemotherapy， endocrine therapy and also the new biological drugs. There is no strong data as to which is the best sequence or for how long these treatments should be given， and we have made a plea for better research through better clinical trials that are well-developed and that will address the different needs of these patients. The guidelines are written in a very practical way where all physicians who treat breast cancer can see the level of evidence for each recommendation and also the percentage of consensus from the panel members and what should be done for each specific subtype of breast cancer with metastasis and also for the group with inoperable locally advanced breast cancer.

　　Cardoso教授：幸运的是，这些发现较早的患者有很多可供选择的药物，比如用于化疗和内分泌治疗的药物，以及其他新的生物制剂，然而，目前尚缺乏有力证据支持采用何种用药顺序或用药疗程。因此我们殷切希望未来有更好、更完善的临床试验能解决患者的不同需求。这些指南非常实用，所有乳腺癌科肿瘤医师都可以看到各项推荐的证据等级和评审委员会的共识比率，还可以看到针对各种伴有转移的乳腺癌亚型，以及无法切除的局部晚期乳腺癌的治疗方案。

　　Oncology Frontier: Are there any particular therapy regimens that you think need more research?

　　《肿瘤瞭望》：您觉得有哪些治疗方案需要进一步研究？

　　Dr Cardoso: I think we need to define newer drugs that can address the issue of resistance. For any drug that we have developed and used so far， tumors have learned to develop resistance to those drugs. Drugs focusing on either delaying or avoiding the onset of resistance are very important. There are new drugs coming out now. One is already available for patients， the other is finishing clinical trials which aim to avoid resistance to endocrine therapy. For example， the combination of everolimus or palbociclib with endocrine agents， seems to be an important step forward. We need to see the confirmation results for palbociclib later this year but everolimus is now available and there is a recommendation from the panel on how to best use that drug. It is unfortunate that it is a drug with side effects and cannot be used for all ER-positive patients but a decision should be made on a case-by-case basis. Another area of intense research and where two new drugs have reached the market is the HER2-positive population with TDM1 and pertuzumab being added to the already existing trastuzumab and lapatinib. The issue here is how to best sequence these drugs and how to best select each patient for the necessary treatment or combination of treatments.

　　Cardoso教授：我认为我们需要研究能够应对耐药的新药。目前乳腺癌细胞已经对我们所采用的所有药物都产生了耐药。因此研发能推迟或避免耐药发生的新药，显得尤为关键。目前一些新药正陆续问世，其中一些已经在临床应用。已完成的临床试验显示，该类新药可以避免发生内分泌治疗耐药。比如将依维莫司或palbociclib同内分泌治疗联合运用，这是我们向前迈出的重要一步。关于palbociclib，我们仍需要等待今年年底的确认结果，而依维莫司已经上市，并且指南中已经有了该药的最佳使用方案推荐。遗憾的是，由于不良反应，这类药物不适合用于所有的ER阳性患者，需根据具体病例具体分析。还有一个有趣的研究领域，并已有两类新药问世。该领域研究的是将T-DM1和帕妥珠单抗联合目前已有的曲妥珠单抗和拉帕替尼，用于HER-2阳性患者的治疗。目前尚存的问题是决定最佳的用药顺序，以及怎样为每个患者选择必要的治疗方案或是联合治疗方案。