Oncology Frontier: Dr. Jatoi， what do you think of the evolution of local therapy of breast cancer in the face of improved adjuvant therapies?

　　《肿瘤瞭望》：在辅助治疗不断发展的今天，您如何看待乳腺癌局部手术治疗的发展？

　　Dr. Jatoi: So I think local therapy and adjuvant systemic therapy are complementary. I think there are instances where in the past we had to be very careful about getting wide margins or clear margins around the tumor. I think with improved adjuvant systemic therapy and also adding adjuvant radiotherapy into that， the issue of clear margins around the tumor does not become as overriding an issue as it was several years ago. It has been， as you perhaps know， a decision made by many， and it is a consensus decision， that no tumor on ink is sufficient as a clear margin or a clear surgical marker on the tumor. With better systemic therapy and adjuvant therapy we do not need to go beyond that， we do not need to do more expansive operations because of the effect. We also have good adjuvant systemic therapy and good adjuvant regulatory therapy that complement. We are talking about the fact that we have a pathologist who after you remove the tumor will look at it under the microscope and if there is no tumor on the ink margin I would argue and many others would argue that that is a sufficient local therapy and a sufficient local surgical therapy. Going beyond that is not going to improve outcomes. I think our obsession with going beyond that is no longer necessary because of improvements in adjuvant systemic therapy and radiotherapy， so I think these complementary therapies basically have reduced and helped us dramatically to reduce the risk of local recurrence in breast cancer after breast conserving therapy.

　　Jatoi教授：我认为局部治疗和全身性辅助治疗是互补的。过去在某些情况下，我们需要非常谨慎地确定肿瘤的广泛或清晰边缘。而近几年来，随着全身性辅助治疗的进步及辅助放疗的应用，确定肿瘤的清晰边缘已不再是一个重要问题。正如你可能知道的那样，很多人或共识认为，肿瘤未被墨水浸染足以说明其存在明确的边缘或是手术标记。随着全身性治疗及辅助治疗的优化，我们进行乳腺手术时只需点到为止，而不需进行更广泛的手术。我们目前已有非常好的全身性辅助治疗作为补充。目前，术者切除肿瘤后，病理学家可在显微镜下对肿瘤进行观察，如果肿瘤边缘无墨水浸染，很多人会和我一样认为进行局部治疗及局部手术治疗就已足够，在此基础上进一步扩大治疗并不能改善患者预后。我认为，在这种情况下没有必要一味地追求扩大治疗范围，因为这些辅助治疗基本上可显著降低保乳治疗后乳腺癌的局部复发风险。

　　Oncology Frontier: Can you talk about the effect of localized therapy on breast cancer mortality?

　　《肿瘤瞭望》：能否请您介绍一下局部治疗对乳腺癌死亡率的影响？

　　Dr. Jatoi: There are no randomized trials looking at local therapy of breast cancer versus no local therapy. We have randomized trials looking at local therapy versus local therapy plus adjuvant systemic therapy and we know what the added benefit of adjuvant systemic therapy is beyond local therapy alone but there are no randomized trials looking at breast cancer local therapy versus no local therapy. We do know now from post mastectomy radiotherapy trials that radiotherapy does reduce breast cancer mortality in patients after mastectomy who have high risk tumors. So there does seem to be a clear benefit to local therapy in terms of reducing the risk of mortality. When I say local therapy I mean surgery and radiotherapy. I think this is an important question but to say what effect does local therapy alone versus no local therapy have on breast cancer mortality， we do not have an answer for that question because there have been no trials that address that issue. Such trials would be deemed unethical. We cannot do those kinds of trials.

　　Jatoi教授：目前尚无观察进行与不进行局部治疗时乳腺癌死亡率差异的随机试验。我们曾开展了比较局部治疗及局部治疗加全身性辅助治疗乳腺癌的随机试验，结果发现，与单纯行局部治疗相比，全身性辅助治疗能为患者带来额外获益。但目前并无乳腺癌局部治疗与否的随机对照试验。从有关乳房切除术后放疗试验发现，乳房切除术后放疗可降低高风险乳腺癌患者的死亡率。因此，从这个角度来看，局部治疗（我指的是局部手术治疗与放疗）似乎具有降低乳腺癌死亡率的明确获益。我认为，这是非常重要的问题，但鉴于尚无相关试验，故不行局部治疗与仅局部治疗对乳腺癌死亡率的影响仍无解。因为这种试验不符合伦理要求，所以我们不能开展。

　　Oncology Frontier: In observational studies， contralateral prophylactic mastectomy is often associated with reductions in breast cancer specific in all cause mortality when compared to unilateral surgical treatments alone. Could you talk about these studies and how they compare and contrast?

　　《肿瘤瞭望》：观察性研究发现，与单侧手术治疗相比，对侧预防性乳房切除可降低乳腺癌相关死亡率及全因死亡率。您是如何看待这些研究的？它们是如何比较的？

　　Dr. Jatoi: There have been several studies that have been published in recent years that have looked at patients with unilateral breast cancer who undergone not only unilateral mastectomy but also contralateral prophylactic mastectomy in those who have had bilateral mastectomy or unilateral breast cancer and many of these studies have shown improvements and have shown that contralateral prophylactic mastectomy is associated with improvements in survival. I think there is a strong selection bias with these studies. Now there are patients with unilateral breast cancer who undergo bilateral mastectomy rather than simply unilateral mastectomy. They are perhaps healthier and perhaps come from patients with better access to healthcare. When we compared in these patients， mortality and non-cancer mortality， what we found is that patients with unilateral breast cancer who undergo bilateral mastectomy have lower non-cancer mortality in addition to breast cancer specific in all cause mortality suggesting there is a strong selection bias. Now women who undergo bilateral mastectomy in unilateral breast cancer are a select group of women and probably a healthier core of women who have better access of healthcare. It is very likely that these other factors influence the association between contralateral prophylactic mastectomy and the improvement of breast cancer specific and all cause mortality.

　　Jatoi教授：近几年发表的一些研究，对不仅进行了单侧乳房切除术还同时进行了对侧预防性乳房切除术的单侧乳腺癌患者进行了观察。其中，很多研究表明，在单侧乳房切除术基础上行对侧预防性乳房切除术可改善患者的生存率。我认为，这些研究存在很严重的选择偏倚。与行单侧乳房切除术者相比，行双侧乳房切除术的患者可能更健康，所拥有的医疗资源更好。对上述患者的死亡率及非癌症死亡率进行对比分析可见，行双侧乳房切除术的单侧乳腺癌患者非癌症死亡率以及乳腺癌特异性死亡率均降低，这提示上述研究存在很强的选择偏倚。接受双侧乳房切除术的单侧乳腺癌女性是一组特定人群，其拥有更多医疗资源且通常更健康。而这些因素很可能会影响对侧预防性乳房切除术与乳腺癌性死亡率及全因死亡率改善的相关性。

　　Oncology Frontier： Lastly， Dr. Jatoi， could you talk about the importance about the San Antonio Breast Cancer Symposium? What it means to your specific discipline of medicine and what do you expect this year at the symposium?

　　《肿瘤瞭望》：最后，能否请您谈一下圣安东尼奥乳腺癌研讨会的重要性？其对您所在的具体医学学科有何意义？您对今年的研讨会有何期待？

　　Dr. Jatoi: This is the largest breast cancer meeting in the world. We have scientists， clinicians， practicing doctors coming from all over the world who have an interest in breast cancer and attend the meeting. The meeting includes medical oncologists， radiation oncologists， surgical oncologists， as well as epidemiologists and basic scientists who have an interest in breast cancer. There are going to be a lot of different topics discussed this year. There is going to be an impetus this year I think on breast cancer as a global problem whereas in developing countries for example， you know we see that breast cancer rates are increasing and that is going to be discussed in this meeting. There is also going to be discussions about treating the disease in countries where resources might be limited. For example the use of radial therapy in countries with limited resources is going to be discussed at a satellite symposium. There is going to be discussions on what we just talked about now， contralateral prophylactic mastectomy， why rates are going up in the United States and other parts of the world as well. We have learned in recent years also that breast cancer is a heterogenous disease， that there are probably different subtypes of cancer and so there is going to be discussions about treating these different subtypes of breast cancer in a more targeted manner. That is going to be a topic discussed and in particular there is a lot of interest in what people refer to as triple negative breast cancer. That is estrogen receptor negative， progesterone receptor negative， and Her2 negative breast cancer and there is going to be quite a bit of discussion on where we should go in terms of treating triple negative breast cancer. This is going to be a meeting where there is probably going to be close to 8000 attendees. I think there is going to be a wide array of topics discussed and different perspectives on these issues need to be discussed. Randomized trials which of course are the gold standards for evidence based medicine are going to receive quite a bit of coverage at this meeting and hopefully will play a prominent role in the way we treat breast cancer in the future. As you probably know breast cancer mortality rates have been declining over the last 25 years or so and continued progress in the treatment of breast cancer is going to require well designed randomized trials in the future and the application and results of those trials， in the management of the patient with breast cancer.

　　Jatoi教授：圣安东尼奥乳腺癌研讨会是世界上规模最大的乳腺癌会议，吸引了世界各地对乳腺癌感兴趣的临床医生、科学家、执业医生来参会。对乳腺癌感兴趣的医学肿瘤学家、放射肿瘤学家、外科肿瘤学家、流行病学家及基础科学家都可参会并从中获益。今年的研讨会有很多不同的主题。例如，发展中国家乳腺癌发病率的不断增加是导致乳腺癌已成为全球性问题的重要原动力，今年的研讨会将就发展中国家乳腺癌发病率的增加进行探讨

　　另外，大会还将就一些资源有限的国家中乳腺癌治疗问题进行讨论，例如，将有小型会议专门就放疗在一些资源有限国家中应用进行讨论；大会还将就我们刚刚所谈的对侧预防性乳房切除术在美国及世界其他地区应用率上升原因进行探讨；近年来发现，乳腺癌是一种异质性疾病，可能有不同亚型，故大会还将就不同亚型乳腺癌的更有针对性治疗进行讨论；此外，大会还将就大家目前非常关注的三阴乳腺癌（即雌激素受体阴性、孕激素受体阴性及Her2阴性乳腺癌）及其治疗进行专题讨论。本届圣安东尼奥乳腺癌研讨会参会人数可能会达到近8000人，大会讨论主题非常广泛，将从不同视角对这些话题进行深度讨论。众所周知，随机试验是循证医学的金标准，本次大会上还将发布很多对未来乳腺癌治疗有重要意义的随机临床试验。在过去25余年，乳腺癌死亡率已呈下降趋势，未来我们需开展一些精心设计的随机试验以促进乳腺癌治疗不断进展，并将这些试验结果用于临床乳腺癌患者的管理中。