Ann Oncol:奥拉帕利单一疗法在初治的三阴性乳腺癌患者中的疗效

2021-01-19 MedSci原创 MedSci原创

PARP抑制剂(PARPi)对携带胚系BRCA1/2(gBRCA1/2)突变的乳腺癌患者的抗肿瘤效果是确定的。虽然PARPi单一疗法对BRCA1/2野生型转移性三阴性乳腺癌(TNBC)患者无效,但研究

PARP抑制剂(PARPi)对携带胚系BRCA1/2(gBRCA1/2)突变的乳腺癌患者的抗肿瘤效果是确定的。虽然PARPi单一疗法对BRCA1/2野生型转移性三阴性乳腺癌(TNBC)患者无效,但研究人员推测PARPi可能对没有化疗暴露过的原发性TNBC有效。

在II期PETREMAC试验中,原发性TNBC>2 cm的患者在化疗前接受奥拉帕利治疗长达10周。在奥拉帕利治疗前后收集肿瘤活检组织进行了靶向DNA测序(360个基因)和BRCA1甲基化分析。此外,对治疗前的样本还进行了BRCAness(多重连接依赖探针扩增)、PAM50基因表达、RAD51位点、肿瘤浸润淋巴细胞(TIL)和PD-L1分析。

受试者携带的同源重组基因突变

治疗前肿瘤直径中位数为60 mm(25~112 mm)。32例患者中有18例(56.3%)对奥拉帕利有客观反应(OR)。18例应答者中有10例检测出影响同源重组(HR)的体细胞或胚系突变[OR 55.6%,95% CI 33.7-75.4],而14例无应答者中仅有1例(OR 7.1%;1.3-31.5,P=0.008)。

在不携带HR突变的肿瘤中,6/8的应答者和3/13的无应答者表现为BRCA1高甲基化(P=0.03)。因此,16/18名应答者(88.9%)与4/14名无应答者(28.6%,P=0.0008)携带HR突变和/或BRCA1甲基化。排除1例gPALB2和4例gBRCA1/2突变携带者,12/14名应答者(85.7%)和3/13名无应答者(23.1%,P=0.002)携带体细胞HR突变和/或BRCA1甲基化。与BRCAness签名或基底样亚型不同,低RAD51评分、高TIL或高PD-L1表达均与奥拉帕利疗效相关。

综上,HR缺陷的初治TNBC患者采用奥拉帕利治疗可获得较高的临床应答率

原始出处:

Eikesdal H P,Yndestad S,Elzawahry A et al. Olaparib monotherapy as primary treatment in unselected triple negative breast cancer. Ann Oncol, 2021, 32: 240-249.

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    2021-09-24 minlingfeng
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    2021-01-21 xlysu
  5. [GetPortalCommentsPageByObjectIdResponse(id=2048079, encodeId=d71620480e98e, content=<a href='/topic/show?id=12e49e53102' target=_blank style='color:#2F92EE;'>#阴性乳腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97531, encryptionId=12e49e53102, topicName=阴性乳腺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f65b226, createdName=circumcision, createdTime=Fri Dec 31 08:21:39 CST 2021, time=2021-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1709083, encodeId=8e501e090835b, content=<a href='/topic/show?id=e50536093aa' target=_blank style='color:#2F92EE;'>#单一疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36093, encryptionId=e50536093aa, topicName=单一疗法)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ba7e31580307, createdName=thinkibmz_44722604, createdTime=Thu Jun 24 01:21:39 CST 2021, time=2021-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1865978, encodeId=6eed18659e89e, content=<a href='/topic/show?id=16ce133504e' target=_blank style='color:#2F92EE;'>#Oncol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13350, encryptionId=16ce133504e, topicName=Oncol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b63894, createdName=minlingfeng, createdTime=Fri Sep 24 09:21:39 CST 2021, time=2021-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458799, encodeId=285f1458e9937, content=<a href='/topic/show?id=3ef91982030' target=_blank style='color:#2F92EE;'>#三阴性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19820, encryptionId=3ef91982030, topicName=三阴性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5666112721, createdName=xlysu, createdTime=Thu Jan 21 07:21:39 CST 2021, time=2021-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1571236, encodeId=4f0d15e12360d, content=<a href='/topic/show?id=f42823e48d7' target=_blank style='color:#2F92EE;'>#乳腺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23748, encryptionId=f42823e48d7, topicName=乳腺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37bc15724202, createdName=hanhaisha2013, createdTime=Thu Jan 21 07:21:39 CST 2021, time=2021-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032770, encodeId=358c1032e7047, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Tue Jan 19 19:21:39 CST 2021, time=2021-01-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1038180, encodeId=57da10381806c, content=谢谢梅斯分享这么多精彩信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=anti-cancer, createdTime=Tue Jan 19 19:21:39 CST 2021, time=2021-01-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=918129, encodeId=3b7491812936, content=为什么用单药?, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Tue Jan 19 18:02:12 CST 2021, time=2021-01-19, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=2048079, encodeId=d71620480e98e, content=<a href='/topic/show?id=12e49e53102' target=_blank style='color:#2F92EE;'>#阴性乳腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97531, encryptionId=12e49e53102, topicName=阴性乳腺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f65b226, createdName=circumcision, createdTime=Fri Dec 31 08:21:39 CST 2021, time=2021-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1709083, encodeId=8e501e090835b, content=<a href='/topic/show?id=e50536093aa' target=_blank style='color:#2F92EE;'>#单一疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36093, encryptionId=e50536093aa, topicName=单一疗法)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ba7e31580307, createdName=thinkibmz_44722604, createdTime=Thu Jun 24 01:21:39 CST 2021, time=2021-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1865978, encodeId=6eed18659e89e, content=<a href='/topic/show?id=16ce133504e' target=_blank style='color:#2F92EE;'>#Oncol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13350, encryptionId=16ce133504e, topicName=Oncol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b63894, createdName=minlingfeng, createdTime=Fri Sep 24 09:21:39 CST 2021, time=2021-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458799, encodeId=285f1458e9937, content=<a href='/topic/show?id=3ef91982030' target=_blank style='color:#2F92EE;'>#三阴性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19820, encryptionId=3ef91982030, topicName=三阴性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5666112721, createdName=xlysu, createdTime=Thu Jan 21 07:21:39 CST 2021, time=2021-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1571236, encodeId=4f0d15e12360d, content=<a href='/topic/show?id=f42823e48d7' target=_blank style='color:#2F92EE;'>#乳腺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23748, encryptionId=f42823e48d7, topicName=乳腺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37bc15724202, createdName=hanhaisha2013, createdTime=Thu Jan 21 07:21:39 CST 2021, time=2021-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032770, encodeId=358c1032e7047, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Tue Jan 19 19:21:39 CST 2021, time=2021-01-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1038180, encodeId=57da10381806c, content=谢谢梅斯分享这么多精彩信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=anti-cancer, createdTime=Tue Jan 19 19:21:39 CST 2021, time=2021-01-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=918129, encodeId=3b7491812936, content=为什么用单药?, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Tue Jan 19 18:02:12 CST 2021, time=2021-01-19, status=1, ipAttribution=)]
    2021-01-19 内科新手

    谢谢梅斯提供这么好的信息,学到很多

    0

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    2021-01-19 anti-cancer

    谢谢梅斯分享这么多精彩信息

    0

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    2021-01-19 lovetcm

    为什么用单药?

    0

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三阴性乳腺癌(TNBC)是一种最具侵略性的乳腺癌形式,其占所有确诊乳腺癌病例的15–20%,具有高转移率和高复发率。

JAMA:卡培他滨维持治疗对早期三阴性乳腺癌疗效观察的影响

标准辅助化疗后低剂量卡培他滨维持治疗是否降低早期三阴性乳腺癌复发和死亡的风险?

Cell Metab :邵志敏团队为三阴性乳腺癌“复旦分型”精准治疗策略再添新翼

三阴性乳腺癌作为乳腺癌的其中一种亚型,约占总体乳腺癌人群的10-20%,其雌激素受体、孕激素受体以及人表皮生长因子受体2表达均为阴性。这类乳腺癌恶性程度高,容易出现内脏转移,复发风险大,预后较差。

Lancet:派姆单抗联合化疗一线治疗PD-L1阳性转移性三阴性乳腺癌

对于转移性三阴性乳腺癌并伴有CPS得分10以上的患者,派姆单抗联合化疗可显著提高无进展生存期,派姆单抗可作为PD-L1高表达的转移性三阴性乳腺癌患者一线治疗手段

Eur J Cancer:BRCA1/2突变对三阴性乳腺癌新辅助化疗时发生严重血液毒性风险的影响

BRCA1和BRCA2在DNA修复中起核心作用。因此,携带胚系(g)BRCA1/2突变(m)的患者接受化疗治疗后,发生血液性毒性的风险可能更高。

Cell Death Differ:DYRK2激活HSF1增强对蛋白毒性应激反应的抵抗力并促进三阴性乳腺癌的发生发展

大约90%的实体瘤和75%的造血癌表现出一定程度的非整倍性。既往研究显示,在酵母和哺乳动物系统中,非整倍体细胞相比于整倍体细胞适应性更差。细胞会通过蛋白质降解和折叠途径调节失衡的非整倍体,而这些途径的