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[ABC4]胡夕春教授：乳腺癌精准医疗，有哪些最接地气的基础临床转化研究

2017-11-14 佚名 ioncology

乳腺癌精准医疗基础临床转化研究
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临床中真正实现肿瘤的精准治疗还需要经历漫长的路，众多肿瘤基础研究亟待转化为有效的临床应用。ABC4大会中，全球各地的肿瘤学家对乳腺癌的精准治疗也展开了热议。

临床中真正实现肿瘤的精准治疗还需要经历漫长的路，众多肿瘤基础研究亟待转化为有效的临床应用。ABC4大会中，全球各地的肿瘤学家对乳腺癌的精准治疗也展开了热议。《肿瘤瞭望》在现场采访了复旦大学肿瘤医院胡夕春教授，介绍了目前比较切实可行的乳腺癌精准医疗相关的基础临床转化研究。

PIK3CA、ESR1等基因改变在乳腺癌中的应用

今天下午ABC4介绍了一些基础-临床转化方面的研究，可使临床肿瘤医生从中获益匪浅。首先，来自法国的Fabrice André介绍了利用高通量测序NGS（Next Generation Sequencing）技术进行肿瘤基因检测和发现。虽然NGS真正应用到临床还有很长的路要走，但是某些特别基因，如肿瘤融合基因NTRK等检测，可为临床靶向药物Entrectinib的研发和应用带来新思路。例如非小细胞肺癌患者若存在ALK融合基因突变，选择克唑替尼治疗是可以获益的。我们希望乳腺癌也能发现此类基因突变，以指导更进一步的精准靶向治疗，即筛选出相应可以临床获益的患者。

PIK3CA突变影响肿瘤细胞周期、生存、生长和增殖。人类肿瘤中能经常发现这类突变，包括激素受体阳性（ER+）、人表皮生长因子受体2阳性（HER2+）和三阴性乳腺癌。PIK3抑制剂的相关临床研究BELLE-1和BELLE-2发现，相较于血液ctDNA野生型PIK3CA患者，突变型的PIK3CA患者对PIK3抑制剂（Taselisib）是可以获益的。

第二个具有临床应用价值的是雌激素受体α编码基因（ESR1）。BOLERO-2临床试验中对库存肿瘤标本进行了二次分析发现，在接受过非甾体芳香酶抑制剂（aromatase inhibitor，AI）治疗的转移性乳腺癌患者中普遍存在ESR1基因的突变。存在ESR1突变的患者在AI耐药后更换其他类型的AI内分泌治疗仍无获益。由此可见，ESR1基因突变对解释和指导乳腺癌内分泌治疗耐药具有潜在的应用价值。

ctDNA在乳腺癌中的应用

另一方面的内容主要是英国Nicholas C. Turner教授关于ctDNA，即循环肿瘤基因（circulating tumor DNA）临床应用的介绍。肿瘤细胞体细胞DNA经脱落或者当细胞凋亡后释放进入循环系统，通过ctDNA检测能够检出血液中的肿瘤踪迹，可提示肿瘤是否存在复发转移，一定程度上反映肿瘤细胞的生物学活性及肿瘤负荷，是一种具有定性、定量和追踪的特征性肿瘤标志物。

ctDNA可以检测乳腺癌患者中是否存在上述的PIK3CA、ESR1等基因突变，以阐述肿瘤侵袭、转移或耐药等机制，预测和指导有效的、精准的靶向治疗或内分泌治疗等。此外，也可通过检测ctDNA的丰度来评价治疗的有效性。乳腺癌患者在经过相关治疗后ctDNA检测量若可明显下降，提示该治疗方法有效得当。PALOMA-3研究结果提示，CD4/6抑制剂Palbociclib联合氟维司群（Fulvestrant）内分泌治疗可有效改善HR+/HER2-晚期乳腺癌患者的PFS，且患者的ctDNA检测量明显下降甚至相当时间内检测不到。

乳腺癌精准医学的应用前景

虽然精准医学刚刚起步、方兴未艾，肿瘤的精准治疗在临床中真正地应用还需要经历很长的路。ABC4大会专家投票中也提到，即使NGS和ctDNA等新型检测方法尚未完全准入临床应用中，但其潜在的应用价值是明确的，多数专家支持鼓励患者参与相关临床研究。

通过此次ABC4关于基础-临床转化型研究报告的专场会议，作为一名临床肿瘤医生有机会静下心来仔细聆听，使我们的视野得到拓展；同时也提示肿瘤医生在今后的临床工作中如何有意识的将更多的研究成果转化成有利于乳腺癌患者诊疗的方法。

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    2018-02-04 ms691033630344116

    #转化研究#

    0

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    2018-05-22 cmj21wellington

    #ABC#

    0

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    2018-09-01 ms9833124466084992

    #临床转化#

    0

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    2017-11-16 shijzhiewnjhch

    #精准#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1687179, encodeId=fa9b168e179c8, content=<a href='/topic/show?id=7e2f932944b' target=_blank style='color:#2F92EE;'>#转化研究#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93294, encryptionId=7e2f932944b, topicName=转化研究)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a30c28335723, createdName=ms691033630344116, createdTime=Sun Feb 04 08:10:00 CST 2018, time=2018-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1777074, encodeId=23a41e7707403, content=<a href='/topic/show?id=45ae1e1830' target=_blank style='color:#2F92EE;'>#ABC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1718, encryptionId=45ae1e1830, topicName=ABC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a54039078223, createdName=cmj21wellington, createdTime=Tue May 22 11:10:00 CST 2018, time=2018-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1739794, encodeId=8c721e3979449, content=<a href='/topic/show?id=c8a22306335' target=_blank style='color:#2F92EE;'>#临床转化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23063, encryptionId=c8a22306335, topicName=临床转化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=853b34558513, createdName=ms9833124466084992, createdTime=Sat Sep 01 04:10:00 CST 2018, time=2018-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1403243, encodeId=abcc1403243ec, content=<a href='/topic/show?id=ebbde6353be' target=_blank style='color:#2F92EE;'>#精准#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76353, encryptionId=ebbde6353be, topicName=精准)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83epQX9hfEIBiaPg0e9KvLYVBCSGYydH6K6OQxBh3RaOC0TYP9HYy2v0XdHib1LFnZNU5Siak0P8oh8Aqw/132, createdBy=acd92440184, createdName=shijzhiewnjhch, createdTime=Thu Nov 16 01:10:00 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261531, encodeId=9c602615315f, content=是很好的学习材料.不错.以后会多学习., beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzUn81b5CF5ibVPib8jWI92iciaxmqGHlwruOnK4SVZykd4iahqo1hicklIibyZoxm55X7EM8BW9eX1h1hQ2/0, createdBy=8aa81937526, createdName=李东泽, createdTime=Wed Nov 15 20:39:26 CST 2017, time=2017-11-15, status=1, ipAttribution=)]
    2017-11-15 李东泽

    是很好的学习材料.不错.以后会多学习.

    0