CLIN CANCER RES:Ⅱ/Ⅲ期三阴性乳腺癌患者顺铂,紫杉醇新辅助治疗是否应联合依维莫司

2017-08-20 MedSci MedSci原创

由于肿瘤异质性较强,三阴性乳腺癌靶向治疗一直未取得理想效果。预测治疗反应的分子标志也尚未阐明。CLIN CANCER RES近期发表了一篇文章,研究mTOR抑制剂依维莫司联合顺铂和紫杉醇在三阴性乳腺癌中可以提供协同抗肿瘤作用。

由于肿瘤异质性较强,三阴性乳腺癌靶向治疗一直未取得理想效果。预测治疗反应的分子标志也尚未阐明。CLIN CANCER RES近期发表了一篇文章,研究mTOR抑制剂依维莫司联合顺铂和紫杉醇在三阴性乳腺癌中可以提供协同抗肿瘤作用。

Ⅱ/Ⅲ期的三阴性乳腺癌患者纳入该研究。术前12周每周接受顺铂,紫杉醇治疗并每天接受依维莫司或安慰剂治疗,直到手术。在基线期,1个周期以及手术时收拾肿瘤标本。主要的研究终点为病理完全缓解(pCR)。次要研究终点包括临床反应,保乳率,安全性以及与结果相关的分子特征。2009年-2013年,研究共纳入145例患者。依维莫司组36%的患者达到病理完全缓解,安慰剂组49%的患者达到达到病理完全缓解。两组中,50%的患者通过影像学判断达到完全缓解。依维莫司组观察到的中性粒细胞减少症,黏膜炎以及转氨酶升高更多。对治疗的临床反应以及长期结果与DNA损伤反应基因突变频率增高,三阴性乳腺癌亚型,AR阴性以及高Ki67有关,但是与肿瘤浸润淋巴细胞无关。

文章最后认为,紫杉醇/顺铂联合耐受性及抗肿瘤活性均良好,额外增加依维莫司与不良反应增加有关,并且为改善pCR和临床反应情况。相关研究发现的三阴性乳腺癌预测分子标志可能会影响临床决策,为进一步有临床价值的机制研究提供方向。

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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=550d2008262, createdName=luominglian113, createdTime=Mon Aug 21 16:42:10 CST 2017, time=2017-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235470, encodeId=e3982354e079, content=意思是依维莫司无效?, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfGccQGCB4aeJK5D3ibPlZfB4mO50cwGAa6xz9uorDUr0FT59IwUMUYkiaFauF3AlibI8nVj81lYz9dfMEAp6IOrHX/0, createdBy=74421964351, createdName=ishtar, createdTime=Sun Aug 20 20:12:26 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235445, encodeId=c59a23544508, content=学习了受益匪浅。, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Sun Aug 20 16:36:57 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235428, encodeId=45e52354284e, content=非常好的文章,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7LIiaRZTzJ3SEfiauCzTMPW7YvPPYLNJBXG9oh6Al1icq2VQQkIHWxqXehcicTS62YKJVBhxeth3wggw/0, createdBy=7ce01621306, createdName=天涯183, createdTime=Sun Aug 20 16:09:37 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235391, encodeId=3a0c23539161, content=学习了,很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sun Aug 20 12:59:51 CST 2017, time=2017-08-20, status=1, ipAttribution=)]
    2017-08-22 xlysu
  5. 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channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sun Aug 20 12:59:51 CST 2017, time=2017-08-20, status=1, ipAttribution=)]
  6. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Sun Aug 20 16:36:57 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235428, encodeId=45e52354284e, content=非常好的文章,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7LIiaRZTzJ3SEfiauCzTMPW7YvPPYLNJBXG9oh6Al1icq2VQQkIHWxqXehcicTS62YKJVBhxeth3wggw/0, createdBy=7ce01621306, createdName=天涯183, createdTime=Sun Aug 20 16:09:37 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235391, encodeId=3a0c23539161, content=学习了,很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sun Aug 20 12:59:51 CST 2017, time=2017-08-20, status=1, ipAttribution=)]
    2017-08-21 luominglian113

    学习了,谢谢分享

    0

  7. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Sun Aug 20 16:36:57 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235428, encodeId=45e52354284e, content=非常好的文章,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7LIiaRZTzJ3SEfiauCzTMPW7YvPPYLNJBXG9oh6Al1icq2VQQkIHWxqXehcicTS62YKJVBhxeth3wggw/0, createdBy=7ce01621306, createdName=天涯183, createdTime=Sun Aug 20 16:09:37 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235391, encodeId=3a0c23539161, content=学习了,很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sun Aug 20 12:59:51 CST 2017, time=2017-08-20, status=1, ipAttribution=)]
    2017-08-20 ishtar

    意思是依维莫司无效?

    0

  8. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=550d2008262, createdName=luominglian113, createdTime=Mon Aug 21 16:42:10 CST 2017, time=2017-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235470, encodeId=e3982354e079, content=意思是依维莫司无效?, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfGccQGCB4aeJK5D3ibPlZfB4mO50cwGAa6xz9uorDUr0FT59IwUMUYkiaFauF3AlibI8nVj81lYz9dfMEAp6IOrHX/0, createdBy=74421964351, createdName=ishtar, createdTime=Sun Aug 20 20:12:26 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235445, encodeId=c59a23544508, content=学习了受益匪浅。, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Sun Aug 20 16:36:57 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235428, encodeId=45e52354284e, content=非常好的文章,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7LIiaRZTzJ3SEfiauCzTMPW7YvPPYLNJBXG9oh6Al1icq2VQQkIHWxqXehcicTS62YKJVBhxeth3wggw/0, createdBy=7ce01621306, createdName=天涯183, createdTime=Sun Aug 20 16:09:37 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235391, encodeId=3a0c23539161, content=学习了,很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sun Aug 20 12:59:51 CST 2017, time=2017-08-20, status=1, ipAttribution=)]
    2017-08-20 131****1460

    学习了受益匪浅。

    0

  9. 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channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sun Aug 20 12:59:51 CST 2017, time=2017-08-20, status=1, ipAttribution=)]
    2017-08-20 天涯183

    非常好的文章,学习了

    0

  10. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Sun Aug 20 16:36:57 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235428, encodeId=45e52354284e, content=非常好的文章,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7LIiaRZTzJ3SEfiauCzTMPW7YvPPYLNJBXG9oh6Al1icq2VQQkIHWxqXehcicTS62YKJVBhxeth3wggw/0, createdBy=7ce01621306, createdName=天涯183, createdTime=Sun Aug 20 16:09:37 CST 2017, time=2017-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235391, encodeId=3a0c23539161, content=学习了,很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sun Aug 20 12:59:51 CST 2017, time=2017-08-20, status=1, ipAttribution=)]
    2017-08-20 1ddf0692m34(暂无匿称)

    学习了,很好

    0

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对BRCA1或BRCA2(BRCA1/2)突变携带者,通过二次突变恢复肿瘤BRCA1/2功能被认为是铂类以及PARP抑制剂治疗抵抗的机制之一。CLIN CANCER RES近期发表了一篇文章,研究对新辅助铂基化疗反应差的新发BRCA1/2突变乳腺癌的治疗抵抗机制。

JAMA:三阴性乳腺癌免疫浸润与何相关?

为什么有些三阴性乳腺癌(TNBCs)有高而其他有低的免疫细胞浸润呢?关于这一点目前知之甚少。了解免疫监视如何塑造癌症基因可能有助于区分病人和制定更有效的免疫治疗策略。为了检测TNBCs中基因组中度量与免疫浸润程度的关系,Thomas Karn等人进行了相关研究。

Lancet oncol:Ipatasertib联合紫杉醇对转移性三阴性乳腺癌的治疗效果。

三阴性乳腺癌是指癌组织免疫组织化学检查结果为雌激素受体(ER)、孕激素受体(PR)和原癌基因Her-2均为阴性的乳腺癌。这类乳腺癌占所有乳腺癌病理类型的10.0%~20.8%,具有特殊的生物学行为和临床病理特征,预后较其他类型差。

CANCER RES:三阴性乳腺癌高表达CDK7与不良预后有关,可作为治疗靶点

三阴性乳腺癌(TNBC)患者预后往往较差,治疗后复发率较高,但是对于该疾病尚缺乏分子标志和有效的靶向治疗。CANCER RES近期发表了一篇文章,研究细胞周期相关酶CDK7作为三阴性乳腺癌潜在治疗靶点的可行性。

PLoS Genet:三阴性乳腺癌与同源重组缺陷有关!

三阴性乳腺癌(TNBC)是指癌组织免疫组织化学检查结果为雌激素受体(ER)、孕激素受体(PR)和原癌基因Her-2均为阴性的乳腺癌。临床表现为一种侵袭性病程,其远处转移风险较高,内脏转移机会较骨转移高,脑转移几率也较高,预后较其他类型差。

JAMA Oncology:三阴性乳腺癌基因突变状态、病理完全缓解与无病生存

GeparSixto临床试验结果表明在蒽环类药物、紫杉烷以及贝伐单抗组成的治疗方案外额外增加卡铂辅助治疗可以三阴性乳腺癌患者病理完全缓解(pCR)率。但是BRAC1和BRAC2基因突变状态是否会影响治疗结果尚不明确。JAMA Oncology近期发表了一篇文章,研究三阴性乳腺癌患者BRAC1和BRAC2基因突变状态是否影响治疗反应。