乳腺癌分子靶向药物治疗进展

《乳腺癌分子靶向药物治疗进展》由会员上传分享，免费在线阅读，更多相关内容在教育资源-天天文库。

1、乳腺癌分子靶向药物治疗进展张清媛哈尔滨医科大学附属肿瘤医院ChemotherapyEndocrinetherapyTargetedtherapiesTreatmentofBCHIGHLIGHTSINBREASTCANCERDISEASEBIOLOGY针对HER2受体的靶向药物针对表皮生长因子受体(EGFR)的靶向治疗针对肿瘤血管生成的分子靶向药物其他信号通路抑制剂——mTOR，Ras，MEK等乳腺癌分子靶向药物治疗中位生存期的缩短HER2扩增/过度表达3年HER2正常表达6-7年HER2受体过度表达HER2原癌基因

2、扩增HER2在约20%～30%的乳腺癌组织中过度表达SlamonDJetal.Science1987;235:177–82HER2阳性与内分泌治疗及部分化疗耐药密切相关，是重要的预后指标HER2成为乳腺癌治疗的理想靶点，是预测赫赛汀疗效的重要指标赫赛汀(曲妥珠单抗):人源化抗HER2单克隆抗体高度亲和性(Kd=0.1nM)和特异性95%人源化,5%鼠抗，显著降低免疫原性(HAMA)全球第一种治疗实体瘤的单克隆抗体InhibitionofHER2-mediatedsignallingActivationofADCC

3、赫赛汀的作用机制AdditionalmechanismsPreventsformationoftruncatedHER2(p95)InhibitionofHER2-regulatedangiogenesisADCC,antibody-dependentcellularcytotoxicity赫赛汀已成为HER2阳性乳腺癌的基础治疗1stlineHO648gM77001USOncologyBCIRG007CHATTAnDEMRHEARelapse2nd+linesGBG-26BO17929EGF104900Numer

4、ousPhaseIIstudiesMBCProgressionHERANSABPB-31NCCTGN9831BCIRG006AdjuvantNOAHMDACCGeparQuattroNumerousPhaseIIstudiesNeoEBCHER2,humanepidermalgrowthfactorreceptor2EBC,earlybreastcancer;MBC,metastaticbreastcancer>13,000患者入组的赫赛汀四大辅助临床研究Piccart-Gebhartetal2005Romo

5、ndetal2005;Slamonetal2006NCCTGN9831(USA)HERA(ex-USA)BCIRG006(global)NSABPB-31(USA)IHC/FISH(n=5,090)Observation1year2yearsIHC/FISH(n=3,505)1year1yearFISH(n=3,222)1year1yearIHC/FISH(n=2,030)1yearDocetaxelDocetaxel+carboplatinDoxorubicin+cyclophosphamideHercepti

6、nStandardCTxPaclitaxelIHC,immunohistochemistryFISH,fluorescenceinsituhybridisationCTx,chemotherapy赫赛汀可减少三分之一的死亡风险012B-31/N9831ACPH3HERACTxH1year2Medianfollow-up,yearsOverallsurvivalbenefitBCIRG006ACDH3BCIRG006DCarboH3FavoursHerceptinFavoursnoHerceptinHRSl

7、amonetal2006Perezetal2007;Smithetal2007H,Herceptin;AC,doxorubicin,cyclophosphamideP,paclitaxel;D,docetaxel;Carbo,carboplatinHR,hazardratioSizeofsquarerepresentssamplesize;horizontalbarsindicate95%confidenceintervals无论肿瘤大小，赫赛汀均显示DFS获益Slamonetal2006Perezetal

8、2007;Smithetal2007>2-5cmBCIRG006>2-5cm>5cm0.00.52.51.01.52.00-2cmN9831/B-310-2cm>5cmACDH<2cmDCarboH<2cm≥2cm≥2cmFavoursHerceptinFavoursnoHerceptinHRHERADFS,disease-freesurvival无论淋巴