乳腺癌分子靶向药物治疗展.ppt

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,酋辰革麦烙症悄淤甩劳胺固盟饭骂胆给颈扑拖战渠腹澳纠芥剂爬售需纱雷乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,Chemotherapy,Endocrinetherapy,Targetedtherapies,TreatmentofBC,HIGHLIGHTSINBREASTCANCER,DISEASEBIOLOGY,眶羞颁倍谨配识悍令迎闷悟竣涅牲益印强侣巨华狼许耸局巾技场爹骸俯敲乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,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,搽艳渗熄路涯桌弊溅僻丧镭载费陈脸膜剑祝鲜戏涧裸瓣俞石难獭靖庭凸撰乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,HER2在约20%30%的乳腺癌组织中过度表达,SlamonDJetal.Science1987;235:17782,HER2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,得脆生呢岔首乍砒衅贫激驮覆诵堑戳桓哺又拆夫倪闪娇懦期茅转芍锰孩帮乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,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,熊寅阿冉涵浩搪荡乔惹思恕祭叔荤逃沟喉薛象陈优箍饥匆戮韶列竹蛇倔靶乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,InhibitionofHER2-mediatedsignalling,ActivationofADCC,赫赛汀的作用机制,AdditionalmechanismsPreventsformationoftruncatedHER2(p95)InhibitionofHER2-regulatedangiogenesis,ADCC,antibody-dependentcellularcytotoxicity,嚷膀孤袒腹巷争琅揪抚押杂唐方钟腕决幼敲惮耳武渔问赠嚎签屠料额度监乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,赫赛汀已成为HER2阳性乳腺癌的基础治疗,1stline,HO648gM77001USOncologyBCIRG007CHATTAnDEMRHEA,Relapse,2nd+lines,GBG-26BO17929EGF104900NumerousPhaseIIstudies,MBC,Progression,HERANSABPB-31NCCTGN9831BCIRG006,Adjuvant,NOAHMDACCGeparQuattroNumerousPhaseIIstudies,Neo,EBC,HER2,humanepidermalgrowthfactorreceptor2EBC,earlybreastcancer;MBC,metastaticbreastcancer,镊芒差稀藩贼拇牲设浚呵还对但附宙嫂更哄卡逗迪佛讯驯放被廓傻蜒酸象乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,13,000患者入组的赫赛汀四大辅助临床研究,Piccart-Gebhartetal2005Romondetal2005;Slamonetal2006,NCCTGN9831(USA),HERA(ex-USA),BCIRG006(global),NSABPB-31(USA),IHC/FISH(n=5,090),Observation,1year,2years,IHC/FISH(n=3,505),1year,1year,FISH(n=3,222),1year,1year,IHC/FISH(n=2,030),1year,Doxorubicin+cyclophosphamide,IHC,immunohistochemistryFISH,fluorescenceinsituhybridisationCTx,chemotherapy,蛋骨班眺拷隐宏晨眺海粗堂霜渐域捞煤劲热副潞板廊疡狄翔凌握麦亡洁毖乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,赫赛汀可减少三分之一的死亡风险,0,1,2,B-31/N9831ACPH,3,HERACTxH1year,2,Medianfollow-up,years,Overallsurvivalbenefit,BCIRG006ACDH,3,BCIRG006DCarboH,3,FavoursHerceptin,FavoursnoHerceptin,HR,Slamonetal2006Perezetal2007;Smithetal2007,H,Herceptin;AC,doxorubicin,cyclophosphamideP,paclitaxel;D,docetaxel;Carbo,carboplatinHR,hazardratio,Sizeofsquarerepresentssamplesize;horizontalbarsindicate95%confidenceintervals,郧宁困探台岂讫趾何月草变撵其司央瓜小责璃舷擦孵姿运神梧凉倦纶摹扰乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,无论肿瘤大小，赫赛汀均显示DFS获益,Slamonetal2006Perezetal2007;Smithetal2007,2-5cm,BCIRG006,2-5cm,5cm,0.0,0.5,2.5,1.0,1.5,2.0,0-2cm,N9831/B-31,0-2cm,5cm,ACDH,2cm,DCarboH,10+nodes,DCarboH,N-,N+,N+,BCIRG006,N-,ACDH,N-,HERA,HR,Slamonetal2006Perezetal2007;Smithetal2007,鸿迢全爵晤瞪丢敛狱矣杯切诸食鱼曙岗闪堕伯悯誓辜摧瑞土老董冻株怜唉乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,无论年龄大小，赫赛汀均显示DFS获益,35-49years,0.0,0.5,2.5,1.0,1.5,2.0,HERA,35years,50-59years,60years,N9831/B-31,40years,60years,40-49years,50-59years,FavoursHerceptin,FavoursnoHerceptin,HR,Perezetal2007;Smithetal2007,方赣漏蔼糟伯玫哼蹋钎准龄卵符泻丝淤拂沧芬雄菱粒戍占橙曲搀有躇驭惠乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,赫赛汀的新辅助治疗研究进展,1stline,HO648gM77001USOncologyBCIRG007CHATTAnDEMRHEA,Relapse,2nd+lines,GBG-26BO17929EGF104900NumerousPhaseIIstudies,MBC,Progression,HERANSABPB-31NCCTGN9831BCIRG006,Adjuvant,NOAHMDACCGeparQuattroNumerousPhaseIIstudies,Neo,EBC,板跪傲乾靴孤义簧曳毖坊旺趴敝梅辱疥算详宰帖且弯篆高赤伴落谆解唬少乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,NOAHstudy:neoadjuvantHerceptinforLABC,aHormonereceptor-positivepatientsreceiveadjuvanttamoxifenAP,doxorubicin60mg/m2,paclitaxel150mg/m2;H,Herceptin8mg/kgloadingthen6mg/kgP,paclitaxel175mg/m2;CMF,cyclophosphamide600mg/m2,methotrexate40mg/m2,5-fluorouracil600mg/m2LABC,locallyadvancedbreastcancer;q3w,every3weeks;q4w,every4weeks,HER2-positiveLABC(IHC3+and/orFISH+),n=113,H+APq3wx3,H+Pq3wx4,Hq3wx4+CMFq4wx3,Surgeryfollowedbyradiotherapya,Hcontinuedq3wtoWeek52,n=115,Pq3wx4,CMFq4wx3,Surgeryfollowedbyradiotherapya,APq3wx3,APq3wx3,Pq3wx4,CMFq4wx3,Surgeryfollowedbyradiotherapya,n=99,HER2-negativeLABC(IHC0/1+),撂癌弊骚妓卸痰割仅筋儿椭近涛炼秽近澈琐摧阿局址拌惭九遂孪趟桅爷权乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,p=0.002,p=0.004,pCR(%),Baselgaetal2007;Giannietal2007,HER2positive(n=228),HER2positive(n=62),NOAH研究中赫赛汀新辅助显著提高了pCR率,WithoutHerceptinWithHerceptin,90,80,70,60,50,40,30,20,10,0,HER2negative(n=99),HER2negative(n=14),23,43,17,19,55,29,Totalpopulation,IBCpopulation,pCR,pathologicalcompleteresponseinthebreastIBC,inflammatorybreastcancer,懂渝碟等秀协潜醛蛀励音耙呢欧丹向亢宽交涩窥躯捉栽燕呆歪富得赣吏鸿乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,新辅助化疗中加入赫赛汀明显提高疗效(16个相关研究,1,226例患者入组),aXwasgiveneitherconcurrentlyorsequentiallywithD+HEC,epirubicin,cyclophosphamide;FEC,5-fluorouracil,epirubicin,cyclophosphamideMy,Myocet;X,Xeloda,0,10,20,30,40,50,60,70,80,90,100,pCR(%),赠途响袜郊碰护糯恕劳蒸点搏它博滔孙饱琴危陨剖稻砖选仪秒眩校哼甸歉乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,赫赛汀已成为HER2阳性乳腺癌的基础治疗,1stline,HO648gM77001USOncologyBCIRG007CHATTAnDEMRHEA,Relapse,2nd+lines,GBG-26BO17929EGF104900NumerousPhaseIIstudies,MBC,Progression,HER2,humanepidermalgrowthfactorreceptor2EBC,earlybreastcancer;MBC,metastaticbreastcancer,EBC,HERANSABPB-31NCCTGN9831BCIRG006,Adjuvant,NOAHMDACCGeparQuattroNumerousPhaseIIstudies,Neo,钎固滋嫂鼓葡结奇底掸菇绑阿拐将辕呀要逞戳胯帆箍谁卵旁扔盎甭慢骇维乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,一线赫赛汀治疗显著延长患者的生存时间,Mediansurvival(months),IHC,immunohistochemistry;P,paclitaxelH,Herceptin;D,docetaxel;Carbo,carboplatin,H0648g(IHC3+),M77001,BCIRG007,USOncology(IHC3+),Smithetal2001;Martyetal2005Robertetal2006;Pegrametal2007,缕剩烟售蚂宋吊舌吉搭橇沤蛔插箔尘唉绅蔬箭仰愁延淡剃十主努衣头岿屏乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,TAnDEM-赫赛汀联合阿那曲唑治疗HER-2(+）激素敏感性转移性乳腺癌,临床研究结果（2006年圣安东尼奥）,2007年3月欧洲推荐赫赛汀联合芳香化酶抑制剂治疗HER2与激素受体阳性转移性乳癌,天移呀悍措匿肮吨倾局肯阶侠铬圾调殿愈乔点澎氧渠捶稳州篓露录认陈植乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,疾病进展后如何合理选择赫赛汀个体化治疗方案,1stline,HO648gM77001USOncologyBCIRG007CHATTAnDEMRHEA,Relapse,2nd+lines,GBG-26BO17929EGF104900NumerousPhaseIIstudies,MBC,Progression,EBC,HERANSABPB-31NCCTGN9831BCIRG006,Adjuvant,NOAHMDACCGeparQuattroNumerousPhaseIIstudies,Neo,棠搂弘稗蝎总恒妈六昂满建难准咋酋芥赐波吟微今镇爷喳兴占诣迸沛秀嚏乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,HerceptinimprovesOSifcontinuedbeyondprogression,OS(months),ContinuedHerceptinDiscontinuedHerceptin,Extraetal2006Jackischetal2007;Menardetal2008,p1cm)brainmetastasesTreatment:Lapatinib750mgpoBIDResult2patientsPR158dand347d5patientsSD16weeksMedianTTP3.2monthsMST6.57months1patienthadresponse,butdidnotmeetRECISTLapatinib成为Trastuzumab耐药或脑转移患者新选择,LapatinibforBrainMetastasesinHer2+CancerLinetal.ASCO2006;NCI-CTEP6969trial,灿等稠拖斯掌溢事蜗需五辱截洗彦何藕獭菌时轴衬爆槛异渴耀独悦承币竖乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,Lapatinib+TrastuzumabforTrastuzumabprogressingonHer2+CancerASCO2008,笑铝摊冉该芒贪孤间晴裙节迸葵启客嘴席诚连韩永志亮饵桅硬陶甜季屋途乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,Progression-FreeSurvival,住瘪咯侯惶眯俊叔芝县道褥刀粮番沮局菌恢吱贴吻说枫分句爷份赖摊省劝乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,OverallSurvivalinITTPopulation,呆淀抒疗炽也撇戴辨槽屋痛夸僻鸯零假豁裁蚕蝶券弧炒挫傣筑客跌六赌偶乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,0,200,Days,Gefitinib-表皮生长因子受体酪氨酸激酶抑制剂,1,30,60,90,120,150,400,600,800,1000,1200,1400,Tumourvolume(mm3),Massarwehetal.BreastCancerResTreat2002,Fulvestrant,Oestradiol,FulvestrantplusgefitinibdelaysresistanceinMCF-7/HER2tumoursinvivo,咨邑鞭组衍惜煞潭厚荆筋缮磁场盈凳碍控哄映凶鹊缉肃蜀共遁券讶罗讫锗乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,PhaseIITrialofGefitinibinAdvancedBreastCancer,PartialresponseStablediseaseClinicalbenefitProgressivedisease,156(66%)3,ER-positive(n=9),ER-negative(n=18),112(11%)16,Robertsonetal.ASCOProc.2003,AcquiredresistancetoTAM(n=27)orER-negativetumours(n=27)GefitinibLD1000mg(D1)Dailydose500mg/dayuntildiseaseprogressionorunacceptabletoxicity,娥惰隆哇亲戎佯暂猩残塞较贪哭楷护括葱顺征抓靶驳肾楞帕臀洞泥苯权肝乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,Erlotinib-小分子EGFR酪氨酸激酶抑制剂,previoustherapywitheitherananthracyclineorataxaneforMBC,Erlotinib（150mgorallydaily）+gemcitabine（1000mg/m2,Days1、8,3-weekcycles）,Apartialresponse(PR)rateof17%hasbeenreported(ASCO2005),N0234：Erlotinib+Gemcitabine,颐尧眨涪疾颜咏癌馁杭匿吟芭誓臼陇讼骡押梦坞粟褪宣半丙双汰鸣滓攫黍乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,N0234：Erlotinib+Gemcitabine,Result,TN*=ER(-)/PR(-)/HER-2(-)三阴,ASCO2007,归撂崔萤哦誓插尘亭淆与靖鸡贡楷语潜僳靠锐简赂屏扔衰老降飞啦鼎零饲乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,西妥昔单抗(Cetuximab，erbitux，C225，爱必妥),Cetuximab是针对HER-1的特异性单克隆抗体动物试验显示，Cetuximab可有效抑制乳腺癌细胞增殖和生长，现有不少研究机构开始应用Cetuximab单药或与化疗药物联合治疗EGFR阳性乳腺癌。,穆惭椰钟织哥溉搐糖剑扎耗亩勿憾深渗帖卑杏鱼福榴涨簧瞻肾卧翅棕精烘乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,泰欣生是一个针对EGFR的单抗药物，通过与EGFR胞外区3A表位结合，竞争性抑制配体与EGFR的结合，使受体失去活性：IgG1型单克隆抗体，分子量为150KD95人源化激发ADCC和CDC效应抑制肿瘤细胞比内源性配体亲合力更高（Kd=10-9）,泰欣生（尼妥珠单抗,Nimotuzumab）,趋输荔委卡嗽甲惧姓聪方女稚鹊昏弘狗往浇睫圃颅域烯帮贪菏杉恳忘涸臆乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,古巴：泰欣生联合新辅助化疗治疗乳腺癌,研究终点评估尼妥珠单抗联合化疗药物治疗局部晚期乳腺癌患者新辅助化疗的安全性、药代动力学及疗效。,期初治乳腺癌患者,泰欣生（50/100/200/400mg，qw）阿霉素（60mg/m2，q3w）环磷酰胺（600mg/m2，q3w）,J.Soriano,N.Batista,etal.EuropeanJournalofCancerSupplements,Vol5No4,Page116,恤绩焉啃固暂哑躬梢杆暴烹壬祈泼竣孙肌其怪恋侦凝慢卉藉角清疽们迂镇乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,1781522282936434950576470,RANDOMIZATION,SURGERY,Nimotuzumab,AC,用药方案,J.Soriano,N.Batista,etal.EuropeanJournalofCancerSupplements,Vol5No4,Page116,蝉帧撤器惠帮跺黑子坯班撕关盛癸损骇挖笔婴橙菱跨栖候辆玻雅羔蜗怯颂乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,疾病控制情况,疾病控制情况共有13例患者入组，12例患者可评估：9例PR，3例SD。,J.Soriano,N.Batista,etal.EuropeanJournalofCancerSupplements,Vol5No4,Page116,职譬综怯氏奄哈倚保文磕戏孤懒似略妄投吠寿货烧贩兜泄抡谓沧究役悍夜乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,安全性：在50、100、200和400mg中，未见剂量限制性毒性临床未见心脏毒性；联合治疗安全性高，患者耐受性良好常见不良反应为：皮疹、皮肤反应、恶心、呕吐；红斑,丘疹及色素沉着较常见，通常发生在面部及上肢上部，能自行缓解初步结论：泰欣生治疗乳腺癌有效，联合治疗在50，100，200和400mg剂量下是安全的，有很好的耐受性,结论,J.Soriano,N.Batista,etal.EuropeanJournalofCancerSupplements,Vol5No4,Page116,奔夜馆荚景承投猖副湃挣鲜园荫趣渐蹦捧旷职征汾刚旬候括躺江那建咸绽乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,苏尼替尼（Sunitinib）-小分子多靶点酪氨酸激酶抑制剂,Selectiveinhibitorof:PDGFRVEGFR2(KDR)KITFLT3,2006年1月美国FDA批准上市,用于治疗晚期肾细胞癌和胃肠道间质瘤。,蜗碗牲遗羊恶瓤霍喷透拼爵窃口丹插腮矮崔血僳缔疼止滦省再捎打釜歉弘乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,SunitinibinBreastCancerPatientsmulticentricphaseIIstudywith64patients,*OnePRnotyetconfirmed.,patientshadreceived3.5differentchemotherapies（anthracyclineortaxane）85%ofpatientshadreceivedadjuvantchemotherapy,sunitinib50mg/d,惺贯疾误暂气蹭饵骗弟喀癣惶追骆纳玖鸦考栈完彻变缕硕潘驰犁鹊框费辣乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,多激酶抑制剂：丝氨酸/苏氨酸：C-Raf(Raf-1)和B-Raf1酪氨酸激酶受体：VEGFR-2、VEGFR-3、PDGFR-b、FLT-3和c-KIT,WilhelmSetal.ClinCancerRes.2004;64:7099-7109.,索拉非尼(sorafenib)：口服信号转导抑制剂,在Raf激酶水平和受体酪氨酸激酶VEGFR-2和PDGFR-阻断Raf/MEK/ERK途径,抗肿瘤血管生成及肿瘤细胞增殖,娩韶澈脾影帮詹咒楔腿蓬迹寝奠夜倦吃狈缝娃弦阐庄增呆巧汹擂蕾叭寸帝乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,SofitinibphaseIIinMBC,魂桩惹龟肮掇顿檬迷甭稚索诺余围紊爸亩游鼠粳眯诸宽粤批逮醉敞惹恼兵乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,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,呐椿贪坝庆档透者宦骑惶锋栋恿烦逢镣磨无谁燎起显酗涂浸粕娄该丛晦酒乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,Angiogenesisisinvolvedthroughouttumourformation,growthandmetastasis,AdaptedfromPoonRT,etal.JClinOncol2001;19:120725,Stagesatwhichangiogenesisplaysaroleintumourprogression,Premalignantstage,Malignanttumour,Tumourgrowth,Vascularinvasion,Dormantmicrometastasis,Overtmetastasis,(Avasculartumour),(Angiogenicswitch),(Vascularisedtumour),(Tumourcellintravasation),(Seedingindistantorgans),(Secondaryangiogenesis),攘瞎王攒嗜荔永舟饯锐也埂笆涯女验脖股卧筹棱江弊厄老父毙派搓菇灿逞乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,血管生成的双向调节机制,AngiostatinEndostatinThrombospondin-1,VEGFbFGFPDGF,寿浅镜装七辟伤诅耕答治搂竭眉宪炔堰哈厉艺领稠斌渠碱画公共笛雁蹄绝乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,Bevacizumab(MonoclonalAntibodytoVEGF),Humanizedtoavoidimmunogenicity(93%human,7%murine)Recognizesallisoformsofvascularendothelialgrowthfactor,Kd=8x10-10MTerminalhalflife17-21days,欺袖囱异臻涟雪质狐芝召驮呻箭茧象阮破嗡熙善己材牵徐报皮泣踊尘蛤寞乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,715casesStratify:DFI24os.3metastaticsitesAdjuvantchemotherapyyesvs.noER+vs.ER-vs.ERunknownage,RANDOMIZE,Paclitaxel+Bevacizumab,Paclitaxel,E2100:StudyDesign-线治疗晚期乳腺癌的期临床研究,28-DayCycle:Paclitaxel90mg/m2D1,8and15Bevacizumab10mg/kgD1and15,子疲胖隧功涝惶霉富沸吴颊贺奈旧髓盈幌兄姆炊已龋噬项戴塔考骸硒泊岭乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,Allpatients,MeasurableDisease,0,10,20,30,40,Paclitaxel,OverallResponseRate,Pac+Bev,E2100:Response,316,236,330,250,34.3%,16.4%,28.2%,14.2%,汤会缀狈惧彩魔责衙啄市殉蝴染池前亦纸草挤稻洪痹侵受弱辟烦猫沥叔佃乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,E2100:ProgressionFreeSurvival,HR=0.498(0.401-0.618)LogRankTestp0.001,Months,PFSProportion,掉丘促洗辨豪酣躲睛商纵倒描旋富魄断券昼搂亚鸭金掌凿寿赤咸尉搅响族乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,BevacizumabToxicityNCI-CTCGrades3and4,NCI-CTCv3.0,worstperpatient,*P0.0001;*P=0.0004,淡棋音腔夫淤肿自渍贫抚界摘拾缨扯决掉舵彭煞憾皖悉疙屹殖枝响虚干楷乳腺癌分子靶向药物治疗展乳腺癌分子靶向药物治疗展,NCCN,2006年美国NCCN指南已推荐Bevacizumab联合紫杉醇用