[SG-BCC2015]圣加仑会议共同主席Alan S. Coates解读圣加伦共识制定和乳腺癌研究热点 ——访2015年圣加仑乳腺癌奖得主Alan S. Coates博士
编者按:2015年圣加仑乳腺癌奖(St.Gallen International Breast Cancer Award 2015)颁给了Alan S. Coates博士,Coates博士在开幕致辞中回顾了“圣加伦乳腺癌妇女最佳治疗共识形成过程的演变(The evolution of the St.Gallen consensus process for the optimal treatment of women with breast cancer)”。Coates教授是悉尼大学公共健康学院/国家卫生医学研究委员会临床试验中心临床教授,St Gallen早期乳腺癌会议共同主席,他的研究兴趣为国际乳腺癌临床试验研究、肿瘤标志物的疗效预测等。《肿瘤瞭望》现场采访了Coates教授,就圣加伦共识的制定模式、乳腺癌治疗的热点问题询问了Coates教授的意见。
专家投票制定圣加伦共识,汇集各方意见大有裨益
圣加伦共识并非全部基于循证医学证据,共识需要专家投票制定,让那些参与乳腺癌治疗,在不管有无循证医学证据的情况下都必须做出决策的医生参与讨论,以投票的方式进行表决,形成建议或共识供临床医师参考。这种方式可汇集各国参会代表和国际乳腺癌专家组的最佳意见。在过去的十几年间,这种圣加伦共识制定模式汇集了专家们对乳腺癌不同角度的认识,以及乳腺癌采取不同方式治疗的信息。毫无疑问,这种圣加伦共识的制定方式大有裨益。
根据患者的复发风险决定是否进行卵巢功能抑制
乳腺癌内分泌治疗是否该加入卵巢功能抑制(OFS)?Coates博士认为,根据SOFTⅢ期研究结果和SOFT & TEXT研究联合分析结果, 他莫昔芬和芳香化酶抑制剂(AI)联合OFS降低了患者的复发风险。OFS药物价格不高,因此广泛适用于收入低、医疗卫生费用支出水平较低的地区。但OFS并非适合所有患者,低复发风险患者用他莫昔芬治疗已足够,不需添加OFS。
哪部分患者最适合OFS联合他莫昔芬或AI治疗?SOFTⅢ期研究显示,高复发风险患者在OFS治疗中获益最多,因此最适合添加OFS治疗的是高复发风险者,即化疗后未绝经的患者和35岁以下的年轻患者。
从SOFT和TEXT研究的联合分析结果可以看出,OFS联合AI(依西美坦)比OFS联合他莫昔芬效果稍好。但 AI并非适合所有人,低复发风险的患者可用他莫昔芬治疗。在AI治疗费用负担大的地区,如果高复发风险患者能用他莫昔芬联合OFS方案治疗,则已经采取了最先进的内分泌治疗方案。
管腔上皮A型和管腔上皮B型乳腺癌:化疗的作用的多大
管腔上皮A型(luminal A-like)乳腺癌的标准治疗是内分泌治疗,一部分患者被建议内分泌治疗+化疗方案。Coates博士指出,真正的管腔上皮A型的乳腺癌中,需要化疗的高风险患者极少,大多数肿瘤大、肿瘤分级高、淋巴结受累广泛的乳腺癌不是管腔上皮A型。所以,需要化疗的管腔上皮A型乳腺癌是罕见的例外。
许多管腔上皮B型(luminal B-like)乳腺癌应当化疗并能从化疗中获益,但化疗获益幅度可能比较小,是否化疗需要与患者讨论。研究者一直试图找出那些“可用内分泌疗法单独治疗而不需要化疗的患者”,但目前对此尚不确定。现在已经有了一些较为经济的新检测工具可检测低风险患者(尽管其被定义为管腔上皮B型),以避免不必要的过度治疗。但是,如果仅仅根据免疫组化检测(ER、PR、HER2和Ki67)进行乳腺癌分子分型还不够;据此分型选择治疗方式,则结论可能是大多数管腔上皮B型乳腺癌不能从内分泌单独治疗中最大获益,有一部分患者还应增加化疗方案。
访谈原文
Oncology Frontier: Professor Coates, congratulation winning the St. Gallen 2015 Award. Your opening address was on the evolution of the St. Gallen consensus process. We are familiar with the current process of votes, but what was it like in past? What can we learn from such an evolution?
《肿瘤瞭望》:Coates教授,祝贺您获得了2015年圣加仑国际乳腺癌奖。您在开幕致辞中回顾了“圣加伦乳腺癌妇女最佳治疗共识形成过程的演变”,之前圣加伦共识形成过程是怎么样的,为何形成目前专家投票制定圣加伦共识的模式?
Prof Coates: What it does is bring together the best views of a widely representative and international panel, not always based on absolutely hard science, but from people who are involved with the management of breast cancer and have to make decisions with or without available evidence. We have pulled that information together in different ways as we have seen the nature of breast cancer and the way it responds to particular treatments evolve over the last ten or fifteen years. There is no doubt that that has changed a lot.
Coates教授:圣加伦共识并非全部基于循证医学证据,共识需要专家投票制定,让那些参与乳腺癌治疗,在不管有无循证医学证据的情况下都必须做出决策的医生参与讨论,以投票的方式进行表决,形成建议或共识供临床医师参考。这种方式可汇集各国参会代表和国际乳腺癌专家组的最佳意见。在过去的十几年间,这种圣加伦共识制定模式汇集了专家们对乳腺癌不同角度的认识,以及乳腺癌采取不同方式治疗的信息。毫无疑问,这种圣加伦共识的制定方式大有裨益。
Oncology Frontier: Recently, we finally get the results of the famous SOFT trial and the joint analysis of SOFT and TEXT. What’s your view on the necessity for combining ovarian function suppression with tamoxifen or possibly aromatase inhibitors?
《肿瘤瞭望》:最近,SOFTⅢ期试验结果和SOFT和TEXT研究联合分析结果发布,您认为他莫昔芬或芳香化酶抑制剂(AI)有无必要联合卵巢功能抑制(OFS)药物治疗?
Prof Coates: Ovarian function suppression is available and cheap and is therefore widely applicable in areas of low income and low health expenditure. Is it needed for all patients? Clearly not. If tamoxifen is available then women at low risk don’t need anything more than that. On the other hand, it seems to me that the women at higher risk and particularly young women at higher risk and particularly in those where the endocrine effect of chemotherapy has not been sufficient to stop their menstrual function, then they will benefit from the addition of ovarian function suppression. Having given ovarian function suppression, there is no doubt from the combined analysis that there is a slightly better result with the aromatase inhibitor, exemestane, than with tamoxifen. The difference is small just as it is in post-menopausal women comparing tamoxifen and an aromatase inhibitor-based treatment. So the aromatase inhibitors are better but maybe not for everybody. The low-risk women may do just as well on tamoxifen. If tamoxifen is available and ovarian function suppression is available for the higher risks, then you have a viable state-of-the-art treatment which is accessible in many countries of the world that can’t afford aromatase inhibitors.
Coates教授:卵巢功能抑制(OFS)药物价格不高,因此广泛适用于收入低、医疗卫生费用支出水平较低的地区。但OFS并非使用所有患者,低复发风险患者如果能用他莫昔芬治疗,则不需添加OFS。而高复发风险患者(年轻患者,化疗后未绝经的患者)可以从OFS治疗中获益。从SOFT和TEXT研究的联合分析结果可以看出,OFS联合AI(依西美坦)比OFS联合他莫昔芬效果稍好, AI的疗效更好,但是并非适合所有人。低复发风险的患者可用他莫昔芬治疗。在支付不起AI治疗费用的地区,如果高复发风险的患者能得到他莫昔芬联合OFS药物治疗,那么就算是采取最先进的内分泌治疗了。
Oncology Frontier: If that combination is not suitable for the general population, which subgroup of patients is indicated?
《肿瘤瞭望》:哪部分患者最适合OFS联合他莫昔芬或AI治疗?
Prof Coates: From the evidence we have, you would be looking at patients who are at higher risk. You are looking at patients who have ovarian function that has withstood chemotherapy. And you are looking at young patients. These are the patients who appear to me to benefit most from these newer approaches.
Coates教授:根据研究证据,最适合OFS联合他莫昔芬或AI治疗的患者是高复发风险乳腺癌患者,即化疗后未绝经的患者和年轻患者。
Oncology Frontier: Standard therapy of luminal A-like type breast cancer is endocrine therapy. However, it is proposed that some certain luminal A-like breast cancer patients should receive chemotherapy in addition to endocrine therapy. Who would be the exceptions to this proposal?
《肿瘤瞭望》:管腔上皮A型乳腺癌的标准治疗内分泌治疗,一部分患者需要内分泌治疗+化疗,那么,哪些患者需要添加化疗?
Prof Coates: There are very few patients where the pattern shows a clear luminal A and yet the risk is sufficient to want to go on and add chemotherapy. Most of the patients who have large or high-grade tumors and most of the patients who have extensive nodal involvement are not going to be luminal A, so these would be rare exceptions.
Coates教授:真正的管腔上皮A型的乳腺癌中,需要化疗的高风险患者极少,大多数大肿瘤、高分级、广泛淋巴结受累的乳腺癌不是管腔上皮A型。所以,需要化疗的管腔上皮A型乳腺癌是罕见的例外。
Oncology Frontier: In the setting of luminal B-like breast cancer, on the other hand, most patients need chemotherapy. So would you consider some patients can be free of chemotherapy and in what circumstances would that occur?
《肿瘤瞭望》:大部分管腔上皮B型乳腺癌需要化疗,那么是否有一部分患者不需要化疗?
Prof Coates: In luminal B, many patients will require the addition of chemotherapy or certainly benefit from the addition of chemotherapy.The magnitude of that benefit may be small and would need to be discussed with the patient. We are always looking for patients who could be spared chemotherapy and we are not in a position to be absolute about that yet. It seems to me that some of the newer tests where available and affordable, will help to identify women who may be at low risk despite the other features that put them in the luminal B group. However, if you are limited to the types of test that are based on immunohistochemistry, then most patients who show up with luminal B probably won’t get maximum benefit from endocrine therapy alone and those are the ones who might benefit from the addition of some form of chemotherapy.
Coates教授:许多管腔上皮B型乳腺癌应当化疗并能从化疗中获益,但这种获益幅度可能比较小,需要与患者讨论。我们一直试图找出那些“可用内分泌疗法单独治疗而不需要化疗的患者”,但目前对此尚不确定。现在已经有了一些较为经济的新检测工具可检测低风险患者(尽管其被定义为管腔上皮B型)。但是,如果仅仅根据免疫组化检测进行乳腺癌分子分型,并据此选择治疗方式,则结论可能是大多数管腔上皮B型乳腺癌不能从内分泌单独治疗中最大获益,有一部分患者还应增加化疗方案。