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1、早期乳腺癌辅助化疗进展,中国医学科学院肿瘤医院徐兵河,BreastCancerIncidenceTrendsOverTime,CancerIncidenceTrendsinChina20052015IncidenceRatesProjectionbyCancerType,Per100,000,CAGR2.98%,CAGR4.5%,CAGR0.65%,CAGR2.35%,CAGR0.99%,CAGR2.60%,Source:EstimatesofCancerIncidenceinChinafor2000andProjectionsfor2005,YangL,etal.,中国乳腺癌发病概况,每年约
2、有19万新发乳腺癌病例2002年全国乳腺癌年龄标化发病率:18.7/100,000；死亡率:5.5/100,000发病率：城市农村高发年龄段：4550岁,近15年来乳腺癌发病率上升死亡率下降,死亡率下降的原因,早期诊断综合治疗,Thebenefitsofchemotherapydatafromclinicaltrails,EarlyBreastCancerTrialistsCollaborativeGroup(EBCTCG).194randomisedtrialsofadjuvantchemotherapy(CMF,CAF,CEF)orhormonaltherapy(TAM)thatbegan
3、by1995.,Lancet2005,Placebo53.3%,37.1,47.9,Time(years),0,5,15,10,Recurrence(%),15-yeargain12.3%(SE1.6)Log-rank2p0.00001,15-yearprobabilitiesofrecurrenceinwomenaged50years,with/withoutpolychemotherapy,Polychemotherapy41.1%,35.5,24.6,Youngerwomen,35%node-positive;olderwomen,70%node-positive;SE=standard
4、error,EBCTCG.Lancet2005;365:1687-1717,Placebo42.4%,20.4,35.0,Breastcancermortality(%),15-yeargain10.0%(SE1.6)Log-rank2p0.00001,Polychemotherapy32.4%,Time(years),0,5,15,10,15.7,27.1,15-yearprobabilitiesofbreastcancermortalityinwomenaged50years,with/withoutpolychemotherapy,EBCTCG.Lancet2005;365:1687-1
5、717,Youngerwomen,35%node-positive;olderwomen,70%node-positive,15-yeargain4.1%(SE1.2)Log-rank2p0.00001,Placebo57.6%,Polychemotherapy53.4%,48.8,0,5,15,10,35.4,44.1,29.4,15-yearprobabilitiesofrecurrenceinwomenaged50-69years,with/withoutpolychemotherapy,Time(years),EBCTCG.Lancet2005;365:1687-1717,Recurr
6、ence(%),Youngerwomen,35%node-positive;olderwomen,70%node-positive,Placebo50.4%,21.3,38.3,15-yeargain3.0%(SE1.3)Log-rank2p0.00001,Polychemotherapy47.4%,18.7,0,5,15,10,35.4,15-yearprobabilitiesofbreastcancermortalityinwomenaged50-69years,with/withoutpolychemotherapy,Time(years),Youngerwomen,35%node-po
7、sitive;olderwomen,70%node-positive,EBCTCG.Lancet2005;365:1687-1717,Breastcancermortality(%),Placebo45.0%,38.3,26.5,15-yeargain11.8%(SE1.3)Log-rank2p0.00001,15-yearprobabilitiesofrecurrenceinwomenwithER+(orER-unknown)disease,with/without5yearstamoxifen,About5yearstamoxifen33.2%,Time(years),0,5,15,10,
8、15.1,24.7,ER=oestrogenreceptor;10,386women:20%ER-unknown,30%node-positive,EBCTCG.Lancet2005;365:1687-1717,Recurrence(%),15-yeargain9.2%(SE1.2)Log-rank2p0.00001,Placebo34.8%,About5yearstamoxifen25.6%,25.7,0,5,15,10,11.9,8.3,17.8,15-yearprobabilitiesofbreastcancermortalityinwomenwithER+(orER-unknown)d
9、isease,with/without5yearstamoxifen,Time(years),10,386women:20%ER-unknown,30%node-positive,EBCTCG.Lancet2005;365:1687-1717,Breastcancermortality(%),0,1,3,5,4,Time(years),2,5-yeargain11.9%(SE1.0)Log-rank2p0.00001,Nil25.8%,About5yearstamoxifenalone13.9%,5-yearrecurrenceinwomenwithER+(orER-unknown)disea
10、sewithnochemotherapy,with/without5yearstamoxifen,EBCTCG.Lancet2005;365:1687-1717,Recurrence(%),7056women:19%node-positive,0,1,3,5,4,2,5-yeargain10.6%(SE1.5)Log-rank2p0.00001,Chemotherapyalone28.1%,Chemotherapy+about5yearstamoxifen17.5%,5-yearrecurrenceinwomenwithER+(orER-unknown)diseasewithchemother
11、apy,with/without5yearstamoxifen,Time(years),EBCTCG.Lancet2005;365:1687-1717,Recurrence(%),3330women:53%node-positive,Chemotherapyversusendocrinetherapyinthetreatmentofbreastcancer,Inpremenopausalwomen,polychemotherapyimproves15-yearrecurrenceby12.4%andsurvivalby10.0%Inpostmenopausalwomen,15-yeargain
12、sinrecurrenceandsurvivalaresmaller(4.2%and3.0%,respectively)anthracycline-basedpolychemotherapyreducestheannualdeathrateby38%forwomen50yearsandby20%forthoseofage50-69years,EBCTCG.Lancet2005;365:1687-1717,Chemotherapyversusendocrinetherapyinthetreatmentofbreastcancer,InpatientswithER+disease,tamoxife
13、nimproves15-yearrecurrenceby11.8%andsurvivalby9.2%Gainsmadewithtamoxifentreatmentappeartobeirrespectiveofadjuvantchemotherapy,EBCTCG.Lancet2005;365:1687-1717,乳腺癌辅助化疗进展,1960s1970s1980s1990s20002002,手术,CMF1,蒽环类药物AC2,CAF3,FEC4,Dose5,6,CEF1207,15FEC1008EC9,Meta-analysis12,紫杉类药物10,11,13,DI14Sequene生物治疗,1
14、Bonadonna19762B-15,B-231990,20003SECSG19944Coombes1996,5Bonadonna19956Wood19947MA-0519988FASG2001,9Belgium200110CALGB200011B-28200012EBCTCG1998,2000,13TACvsFAC14CALGB974115MA.0510years!,评估紫杉类乳腺癌辅助化疗的随机临床试验,CALGB9344ACvsACPNSABPB-28ACvsACP*ECTOACMFvsAPCMFBCIRG001TACvsFACNSABPB-27ACvsACTPACS01FECvsFEC
15、TECOG2197ATvsACECOG1199ACP3vsP1vsD3vsD1.,T=多西他赛P=泰素*在化疗时同时给予三苯氧胺,紫杉烷辅助化疗荟萃分析:方法,目的:比较含紫杉烷辅助化疗方案与不含紫杉烷辅助化疗方案主要结局指标:OS次要结局指标:DFS,毒性11项随机对照试验,17056名患者平均中位随访54.6个月总结果有利于紫杉烷OS:HR0.81(95%CI,0.75-0.88;p.00001)DFS:HR0.81(95%CI,0.75-0.86;p.00001),Nowak等.ASCO2007.文摘号545.,FiveYearfollow-upofINTC9741:Dose-densechemotherapyissafeandeffective,HudisC,CitronM,BerryD,CirrincioneC,GradisharW,DavidsonN,MartinoS,LivingstonR,IngleJ,PerezE,AbramsJ,SchilskyR,EllisM,CarpenterJ,MussH,NortonL,235:17782,HER2状态:预示肿瘤对治疗的反应,内分泌治疗HER2阳性患者相对耐药CMF方案
