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.ppt

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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Breast Cancer Incidence Trends Over TimeCancer Incidence Trends in China 2005 2015 Cancer Incidence Trends in China 2005 2015 Incidence Rates Projection by Cancer Type Incidence Rates Projection by Cancer TypePer 100,000 CAGR 2.98%CAGR 4.5%CAGR 0.65%CAGR 2.35%CAGR 0.99%CAGR

2、 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:5.5/100,000v 发病率：城市农村v 高发年龄段：45 50 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v 早期诊断 v 综合治疗The benefits of chemotherapy data from clinical trailsn Early B

3、reast 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%37.147.90102030405060Time(years)0 5 15 10Recurrence(%)15-year gain 12.3%(SE 1.6)Log-rank 2p0.0000115-year probabilities of r

4、ecurrence in women aged 50 years,with/without polychemotherapyPolychemotherapy41.1%35.524.6Younger women,35%node-positive;older women,70%node-positive;SE=standard error EBCTCG.Lancet 2005;365:1687-1717Placebo42.4%20.435.00102030405060 Breastcancermortality(%)15-year gain 10.0%(SE 1.6)Log-rank 2p0.00

5、001Polychemotherapy32.4%Time(years)0 5 15 1015.727.115-year probabilities of breast cancer mortality in women aged 50 years,with/without polychemotherapyEBCTCG.Lancet 2005;365:1687-1717Younger women,35%node-positive;older women,70%node-positive010203040506015-year gain 4.1%(SE 1.2)Log-rank 2p0.00001

6、Placebo57.6%Polychemotherapy53.4%48.80 5 15 1035.4 44.129.415-year probabilities of recurrence in women aged 50-69 years,with/without polychemotherapyTime(years)EBCTCG.Lancet 2005;365:1687-1717Recurrence(%)Younger women,35%node-positive;older women,70%node-positivePlacebo50.4%21.338.3010203040506015

7、-year gain 3.0%(SE 1.3)Log-rank 2p0.00001Polychemotherapy47.4%18.70 5 15 1035.415-year probabilities of breast cancer mortality in women aged 50-69 years,with/without polychemotherapyTime(years)Younger women,35%node-positive;older women,70%node-positive EBCTCG.Lancet 2005;365:1687-1717Breastcancermo

8、rtality(%)Placebo45.0%38.326.5010203040506015-year gain 11.8%(SE 1.3)Log-rank 2p0.0000115-year probabilities of 15-year probabilities of recurrence recurrence in women in women with ER+(or ER-unknown)disease,with ER+(or ER-unknown)disease,with/without 5 years with/without 5 years tamoxifentamoxifenA

9、bout 5 years tamoxifen33.2%Time(years)0 5 15 1015.124.7ER=oestrogen receptor;10,386 women:20%ER-unknown,30%node-positive EBCTCG.Lancet 2005;365:1687-1717Recurrence(%)010203040506015-year gain 9.2%(SE 1.2)Log-rank 2p0.00001Placebo34.8%About 5 years tamoxifen25.6%25.70 5 15 1011.98.317.815-year probab

10、ilities of breast cancer 15-year probabilities of breast cancer mortalitymortality in women with ER+(or ER-unknown)disease,in women with ER+(or ER-unknown)disease,with/without 5 years with/without 5 years tamoxifentamoxifenTime(years)10,386 women:20%ER-unknown,30%node-positive EBCTCG.Lancet 2005;365

11、:1687-1717Breastcancermortality(%)01020304050600 1 3 5 4Time(years)25-year gain 11.9%(SE 1.0)Log-rank 2p0.00001Nil25.8%About 5 years tamoxifen alone13.9%5-year recurrence in women with ER+(or 5-year recurrence in women with ER+(or ER-unknown)disease withER-unknown)disease with no chemotherapyno chem

12、otherapy,with/without 5 yearswith/without 5 years tamoxifentamoxifenEBCTCG.Lancet 2005;365:1687-1717Recurrence(%)7056 women:19%node-positive01020304050600 1 3 5 4 25-year gain 10.6%(SE 1.5)Log-rank 2p0.00001Chemotherapy alone28.1%Chemotherapy+about 5 years tamoxifen17.5%5-year recurrence in women wi

13、th ER+(or 5-year recurrence in women with ER+(or ER-unknown)diseaseER-unknown)disease with chemotherapywith chemotherapy,with/without 5 yearswith/without 5 years tamoxifentamoxifenTime(years)EBCTCG.Lancet 2005;365:1687-1717Recurrence(%)3330 women:53%node-positiveChemotherapy versus endocrine therapy

14、 in the treatment of breast cancerl In premenopausal women,polychemotherapy improves 15-year recurrence by 12.4%and survival by 10.0%l In postmenopausal women,15-year gains in recurrence and survival are smaller(4.2%and 3.0%,respectively)l anthracycline-based polychemotherapy reduces the annual deat

15、h rate by 38%for women 50 years and by 20%for those of age 50-69 yearsEBCTCG.Lancet 2005;365:1687-1717Chemotherapy versus endocrine therapy in the treatment of breast cancerl In patients with ER+disease,tamoxifen improves 15-year recurrence by 11.8%and survival by 9.2%l Gains made with tamoxifen tre

16、atment appear to be irrespective of adjuvant chemotherapyEBCTCG.Lancet 2005;365:1687-1717乳腺癌辅助化疗进展1960s 1970s 1980s 1990s 2000 2002 1960s 1970s 1980s 1990s 2000 2002 手术CMF1蒽环类药物AC2,CAF3,FEC4Dose5,6CEF1207,15FEC1008EC9Meta-analysis12紫杉类药物10,11,13DI14 Sequene 生物治疗 1 Bonadonna 1976 2 B-15,B-23 1990,200

17、0 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 years!评估紫杉类乳腺癌辅助化疗的随机临床试验l CALGB 9344 AC vs AC Pl NSABP B-28 AC vs AC P*l ECTO A CMF vs AP CMFl BCIRG 001 TAC vs FACl N

18、SABP B-27 AC vs AC Tl PACS 01 FEC vs FEC Tl ECOG 2197 AT vs ACl ECOG 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:方法l 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u 主要结局指标:OSu 次要结局指标:DFS,毒性l 11 项随机对照试验,17056 名患者l 平均中位随访54.6 个月l 总结果有利于紫杉烷u OS:HR 0.81(95%CI,0.75-0.88;p.00001)u DFS:HR 0.81(95%CI,0.75

19、-0.86;p.00001)Nowak 等.ASCO 2007.文摘号 545.Five Year follow-up of INT C9741:Dose-dense chemotherapy is safe and effectiveHudis 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/NCCTGinvestigatorsHER2+Breast Cancer and Adjuvant TherapyHer-2l Her-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。l Her-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。