现代乳癌内分泌治疗新方法32053.pptx

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1、乳癌内分泌治疗新思路和临床实践乳癌的治疗手段 Surgery 手术 Radiation therapy 放疗 Chemotherapy 化疗 Hormone therapy 内分泌治疗 Biotherapy 生物治疗 New therapies 新的治疗乳癌内分泌治疗的发展19701980 19902000Tamoxifen TamoxifenMAAG新的芳香化酶抑制剂 新的芳香化酶抑制剂Exemestane/MA新的芳香化酶抑制剂 新的芳香化酶抑制剂Tamoxifenpure A.E.?MAI III III III IIIII IIII III IIIII IIIHormone Thera

2、py Response Rate(%)in Different Receptor StatusSurvival by Response Arimidex 1 mg0 020 2040 4060 6080 80100 1000 0 1 1 2 2 3 3 4 4CR or PR CR or PRStable Stable 24 24 wks wksProgression ProgressionYears from Randomisation Years from Randomisation%Survival MAAG Prevention DCIS/Neoadj 5 yearsMetastati

3、cDisease 1st2nd 3rdAdjuvant TAM TAMTAMTAMOVABL三苯氧胺（TAM)最重要的乳癌内分泌治疗药物Tamoxifen for 5 Years vs No TreatmentPercentYearsER+85.2 85.276.1 76.168.2 68.273.7 73.762.7 62.754.9 54.911.5(11.5(SE 0.9)SE 0.9)13.4(13.4(SE 1.1)SE 1.1)13.4(13.4(SE 1.4)SE 1.4)68.2%54.9%0204060801000 5 10 15vsRecurrences Breast De

4、aths0204060801000 5 10 15ER+73.0%64.0%91.4 91.480.9 80.973.0 73.0 87.8 87.873.2 73.264.0 64.03.6(3.6(SE 0.7)SE 0.7)7.8(7.8(SE 1.0)SE 1.0)9.0(9.0(SE 1.4)SE 1.4)vsYearsPercentTamoxifen Adjuvant Therapy for EBC辅助内分泌治疗的决定因素是激素受体状况ER阳性效果最好 8Tamoxifen Adjuvant Therapy for EBC合适的TAM服药时间为5年9Tamoxifen Adjuva

5、nt Therapy for EBC ER阳性无论年龄大小都可用TAM10Tamoxifen Adjuvant Therapy for EBC降低对侧乳癌发生增加子宫内膜癌的风险11Tamoxifen Adjuvant Therapy for EBC ER阳性TAM和化疗合用比单用TAM更有效CAF与TAM 序贯合用比同时效果更好 MAAG Prevention DCIS/Neoadj 5 yearsMetastaticDisease 1st2nd 3rdAdjuvant1 TAM TAMTAMTAMOVABLTamoxifenIndications in Breast Cancer三苯氧胺

6、乳癌内分泌治疗不可动摇的地位！？Survival DataAnastrozole/MAMedian time to death(months)2 year survival rate(%)P 0.05Mean Change in Weight(kg)Mean Change in Weight(kg)+SEM+SEMMonths from Start of Therapy Months from Start of Therapy0 0 1 1 2 2 3 3 4 4 5 5 6 6 9 9-2-2-1-10 01 12 23 34 45 5megestrol acetate 4 x 40 mg

7、megestrol acetate 4 x 40 mg(n=85)(n=85)Arimidex 10 mg(n=92)瑞宁得 瑞宁得 1 1 mg(n=98)mg(n=98)瑞宁得用药9个月没有明显的体重变化 瑞宁得(Arimidex)比 MA 更有效、更安全 瑞宁得(Arimidex)1 mg 在复发转移乳癌治疗中缓解率/临床获益率相当生存期更长耐受性更好 Prevention DCIS/Neoadj5 yearsMetastaticDisease 1st2nd 3rdAIAI AdjuvantTAM TAM TAM TAM1Arimidex in Breast CancerMA MAAna

8、strozole is Superior to Tamoxifen in First Line Therapy（0030）JCO 2000;18:3748*Hazard ratio(tam:Arimidex)1.44,lower CL 1.16.Study powered for equivalence.Median follow-up of 18 months.71%progressedTrial 0030:Kaplan-Meier Curve of Probability of Time to ProgressionArimidex(n=171)Tamoxifen(n=182)Median

9、 TTP*:Arimidex 11.1 monthstamoxifen 5.6 months p=0.005(2-sided)01020304050607080901000 6 12 18 24 30 36 42Time to progression(months)Percentage not progressedAIs is Superior to Tamoxifenas First-line Therapy for Advanced Breast Cancer芳香化酶抑制剂取代三苯氧胺成为标准的一线内分泌治疗 Prevention DCIS/Neoadj5 yearsMetastaticD

10、isease AI 1st2nd 3rdAIAI AdjuvantTAM TAM TAM TAM1Arimidex in Breast CancerMA MARationale for Adjuvant Therapy With Aromatase Inhibitors(AIs)AIs Effective after tamoxifenBetter than tamoxifen first lineWell toleratedMay overcome tamoxifen“resistance”The Gold Standard The Gold Standard Tamoxifen First

11、-Line Letrozole is Anastrozole is=Exemestane is?Neoadjuvant Letrozole is Adjuvant？Anastrozole MilestonesActivated 1996Planned accrual 9366Accrual to date Closed 1999 Ongoing AI Adjuvant Trials:ATAC(Anastrozole)Trialists Group TA.Trialists Group TA.Br J Cancer.2001;85:317.2001;85:317.RANDOMIZESurgeryTamoxifen 20 mg odAnastrozole 1 mg odTamoxifen 20 mg odAnastrozole 1 mg od5 yearsDFS/OS