[COMB2014]鼓励患者直面乳腺癌遗传咨询——Wong Seng Weng教授访谈

作者:  黄醒荣   日期:2014/8/26 18:43:55  浏览量:64730

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编者按:“第二届乳腺癌个体化治疗大会”于8月1~3日在北京顺利召开。会上,来自新加坡的Wong Seng Weng教授作了精彩演讲。Wong Seng Weng是伊丽莎白医疗癌症中心肿瘤学专家及内科主任顾问,擅长成人肿瘤的诊断与治疗,尤其在乳腺肿瘤、肺部肿瘤以及胃肠道肿瘤上有着自己独到的见解。《肿瘤瞭望》就乳腺的诊疗进展、遗传咨询和脑转移等问题采访了Wong教授。

伊丽莎白医疗癌症中心 Wong Seng Weng

  <Oncology Frontier>: What improvements have you seen in your field of breast cancer?

  《肿瘤瞭望》: 请您介绍一下乳腺癌领域的进展?

  Dr Wong: Looking at the advances in the treatment of breast cancer, the most important advance has been in understanding the molecular nature of breast cancer and that it is not a homogenous disease. We now understand that there are different subtypes of disease such as the HER2-positive disease and the endocrine receptor positive disease. What is left is a mixed bag; we call it triple-negative disease. But triple-negative is not defined in a positive way. It is defined by exclusion so is a bit of a mixed basket which is why advances in this particular area of triple-negative breast cancer appear to be fewer.

  Of the three subgroups I have mentioned, it would be the HER2-positive and the estrogen receptor positive subgroups that have seen big advances because we have come to understand the mechanism behind tumor growth. For the HER2-positive breast cancers, we have new agents like pertuzumab to be used together with trastuzumab. Pertuzumab prevents the dimerization of HER2 receptors with other receptors in the HER family which produces better results in first-line treatment. Even for very resistant disease with T-DM1 where the thioether link is able to link a cytotoxic agent with the monoclonal antibody trastuzumab, allowing for a very targeted delivery of cytotoxic to the cell, leads to much improved treatment results. For example, with the PARP inhibitors, which were initially thought to be very effective for the triple-negative disease because we believed DNA repair was a weakness of these types of tumors, we have found that not to be the case because they are not homogenous. It is only as subset of triple-negative tumors that respond to that. So this triple-negative group of breast cancers will only see major advances when we understand how to sub-classify them in a positive sense rather than in a negative sense by exclusion.

  Wong教授:从乳腺癌治疗进展方面来看,最重要的进展是我们认识到了乳腺癌的分子特性以及乳腺癌是一种异质性肿瘤。目前,我们已经知道乳腺癌包括多种亚型,如HER-2阳性乳腺癌和内分泌受体阳性乳腺癌。其他种类乳腺癌可归为一大类,我们称其为三阴乳腺癌。但是,三阴乳腺癌这一概念并不是从正面定义的,它是一种排除性诊断,因此,这种类型带有混杂性质,也正是这一原因导致了三阴乳腺癌这一领域的进展不甚明显。

  HER-2阳性乳腺癌和内分泌受体阳性乳腺癌相关进展最多,目前已经明确了肿瘤的生长机制。对于HER-2阳性乳腺癌,已有新的药物可以与曲妥珠单抗使用,如帕妥珠单抗。帕妥珠单抗可阻止HER2受体与HER家族其他受体发生二聚化,该药可使一线治疗产生更好的疗效。即便对T-DM1耐药性十分显著的肿瘤,帕妥珠单抗的硫醚键可使细胞毒性药物与单克隆抗体曲妥珠单抗连接,从而产生更具靶向性的细胞毒性作用,最终产生更好的治疗效果。在这些领域我们取得了显著进步。

  对于雌激素受体阳性肿瘤,我们目前正遭遇阻力,即便如此,我们也已明确了信号传导通路,由此我们可以使用mTOR阻滞剂阻断mTOR,同样,我们也可对PI3K通路进行阻断从而解除肿瘤对内分泌治疗的耐药性并恢复肿瘤的药物敏感性。

  此外,在预防肿瘤出现内分泌治疗耐药性方面,我们也取得了显著进展,使用CDK4/6阻滞剂可中断细胞周期中的部分磷酸化过程,从而达到克服耐药性的目的,估计这一结果可在1年内实现。

  但对于三阴乳腺癌,目前的形式仍十分严峻。这一类型的进展十分缓慢,我们试图进步,但各种尝试总是以失败告终。例如PARP阻滞剂,由于DNA修复是三阴乳腺癌的薄弱环节,因此起初我们认为该药对这类肿瘤十分有效,但是由于肿瘤具有异质性,PARP阻滞剂并未产生预期疗效,仅有部分三阴乳腺癌可对该药产生反应。因此,对于这部分三阴乳腺癌,只有当我们知道如何通过有效的正面方式对其进行分类,才能取得真正的进展。

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