早期乳腺癌辅助化疗进展.ppt

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1、早期乳腺癌辅助化疗进展早期乳腺癌辅助化疗进展Breast Cancer Incidence Trends Over TimePer 100,000 CAGR 2.98%CAGR 4.5%CAGR 0.65%CAGR 2.35%CAGR 0.99%CAGR 2.60%Source:Estimates of Cancer Incidence in China for 2000 and Projections for 2005,Yang L,et al.中国乳腺癌发病概况中国乳腺癌发病概况v每年约有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:5.5/1

2、00,000v发病率：城市农村v高发年龄段：4550岁v早期诊断 v综合治疗The benefits of chemotherapy data from clinical trailsnEarly Breast Cancer Trialists Collaborative Group(EBCTCG).194 randomised trials of adjuvant chemotherapy(CMF,CAF,CEF)or hormonal therapy(TAM)that began by 1995.Lancet 2005Placebo53.3%37.147.90102030405060Tim

3、e(years)051510Recurrence(%)15-year gain 12.3%(SE 1.6)Log-rank 2p0.00001Polychemotherapy41.1%35.524.6Younger women,35%node-positive;older women,70%node-positive;SE=standard errorEBCTCG.Lancet 2005;365:1687-1717Placebo42.4%20.435.00102030405060Breastcancermortality(%)15-year gain 10.0%(SE 1.6)Log-rank

4、 2p0.00001Polychemotherapy32.4%Time(years)05151015.727.1EBCTCG.Lancet 2005;365:1687-1717Younger women,35%node-positive;older women,70%node-positive010203040506015-year gain 4.1%(SE 1.2)Log-rank 2p0.00001Placebo57.6%Polychemotherapy53.4%48.805151035.444.129.4Time(years)EBCTCG.Lancet 2005;365:1687-171

5、7Recurrence(%)Younger women,35%node-positive;older women,70%node-positivePlacebo50.4%21.338.3010203040506015-year gain 3.0%(SE 1.3)Log-rank 2p0.00001Polychemotherapy47.4%18.705151035.4Time(years)Younger women,35%node-positive;older women,70%node-positiveEBCTCG.Lancet 2005;365:1687-1717Breastcancermo

6、rtality(%)Placebo45.0%38.326.5010203040506015-year gain 11.8%(SE 1.3)Log-rank 2p0.00001About 5 years tamoxifen33.2%Time(years)05151015.124.7ER=oestrogen receptor;10,386 women:20%ER-unknown,30%node-positiveEBCTCG.Lancet 2005;365:1687-1717Recurrence(%)010203040506015-year gain 9.2%(SE 1.2)Log-rank 2p0

7、.00001Placebo34.8%About 5 years tamoxifen25.6%25.705151011.98.317.8Time(years)10,386 women:20%ER-unknown,30%node-positiveEBCTCG.Lancet 2005;365:1687-1717Breastcancermortality(%)010203040506001354Time(years)25-year gain 11.9%(SE 1.0)Log-rank 2p0.00001Nil25.8%About 5 years tamoxifen alone13.9%EBCTCG.L

8、ancet 2005;365:1687-1717Recurrence(%)7056 women:19%node-positive01020304050600135425-year gain 10.6%(SE 1.5)Log-rank 2p0.00001Chemotherapy alone28.1%Chemotherapy+about 5 years tamoxifen17.5%Time(years)EBCTCG.Lancet 2005;365:1687-1717Recurrence(%)3330 women:53%node-positivelIn premenopausal women,pol

9、ychemotherapy improves 15-year recurrence by 12.4%and survival by 10.0%lIn postmenopausal women,15-year gains in recurrence and survival are smaller(4.2%and 3.0%,respectively)lanthracycline-based polychemotherapy reduces the annual death rate by 38%for women 50 years and by 20%for those of age 50-69

10、 yearsEBCTCG.Lancet 2005;365:1687-1717lIn patients with ER+disease,tamoxifen improves 15-year recurrence by 11.8%and survival by 9.2%lGains made with tamoxifen treatment appear to be irrespective of adjuvant chemotherapyEBCTCG.Lancet 2005;365:1687-1717乳腺癌辅助化疗进展乳腺癌辅助化疗进展手术手术CMF1蒽环类药物蒽环类药物AC2,CAF3,FEC

11、4Dose5,6CEF1207,15FEC1008EC9Meta-analysis12紫杉类药物紫杉类药物10,11,13DI14 Sequene 生物治疗生物治疗 1 Bonadonna 1976 2 B-15,B-23 1990,2000 3 SECSG 1994 4 Coombes 1996 5 Bonadonna 1995 6 Wood 1994 7 MA-05 1998 8 FASG 2001 9 Belgium 2001 10 CALGB 200011 B-28 200012 EBCTCG 1998,200013 TAC vs FAC14 CALGB 974115 MA.05 10

12、 years!评估紫杉类乳腺癌辅助化疗的评估紫杉类乳腺癌辅助化疗的随机临床试验随机临床试验lCALGB 9344 AC vs AC PlNSABP B-28 AC vs AC P*lECTO A CMF vs AP CMFlBCIRG 001 TAC vs FAClNSABP B-27 AC vs ACTlPACS 01 FEC vs FEC TlECOG 2197 AT vs AClECOG 1199 ACP3 vs P1 vs D3 vs D1l.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紫杉烷辅助化疗荟萃分析:方法方法l目的目的:比较含紫杉烷辅助化疗方案与不含

13、紫杉烷比较含紫杉烷辅助化疗方案与不含紫杉烷辅助化疗方案辅助化疗方案u主要结局指标主要结局指标:OSu次要结局指标次要结局指标:DFS,毒性毒性l11项随机对照试验项随机对照试验,17056名患者名患者l平均中位随访平均中位随访54.6个月个月l总结果有利于紫杉烷总结果有利于紫杉烷uOS:HR 0.81(95%CI,0.75-0.88;p.00001)uDFS:HR 0.81(95%CI,0.75-0.86;p.00001)Nowak 等等.ASCO 2007.文摘号文摘号 545.Five Year follow-up of INT C9741:Five Year follow-up of I

14、NT C9741:Dose-dense chemotherapy is safe and Dose-dense chemotherapy is safe and effectiveeffectiveHudis C,Citron M,Berry D,Cirrincione C,Gradishar W,Davidson N,Martino S,LivingstonR,Ingle J,Perez E,Abrams J,Schilsky R,EllisM,Carpenter J,Muss H,Norton L,&Winer EOn behalf of CALGB/ECOG/SWOG/NCCTGinve

15、stigatorsHER2+Breast Cancer HER2+Breast Cancer and Adjuvant Therapyand Adjuvant TherapylHer-2是一种原癌基因，该基因与乳腺癌细胞增殖有关。l约2530%的乳腺癌Her-2过度表达。lHer-2的过度表达的乳腺癌患者生存期短，预后差。l成为乳腺癌治疗的理想靶点。HER2HER2阳性对生存期的影响阳性对生存期的影响HER2HER2阳性的乳腺癌患者的生存率降低！阳性的乳腺癌患者的生存率降低！中位生存期中位生存期HER2 HER2 阳性阳性3 3 年年HER2 阴性阴性67 年年Slamon DJ et al.

16、Science 1987;235:17782HER2 HER2 状态状态:预示肿瘤对治疗的反应预示肿瘤对治疗的反应 内分泌治疗内分泌治疗 HER2HER2阳性患者相对耐药阳性患者相对耐药 CMFCMF方案方案 HER2HER2阳性患者相对耐药阳性患者相对耐药 蒽环类蒽环类 对蒽环类相对敏感对蒽环类相对敏感 紫杉类药物紫杉类药物相对敏感相对敏感l全球第一种治疗实体瘤的单克隆抗体，为全球第一种治疗实体瘤的单克隆抗体，为HER2HER2癌基因癌基因阳性的肿瘤患者带来了新的希望！阳性的肿瘤患者带来了新的希望！lTrastuzumab是包含了完整的muMAB 4D5抗原决定簇的人类IgG1的人体球蛋白Killer cellKiller cellMacrophageMacrophageHerceptinHerceptin stimulates ADCCstimulates ADCC(antibody-dependent cell-mediated cytotoxicity)(antibody-dependent cell-mediated cytotoxicity)Fc receptorFc re