乳腺癌辅助内分泌治疗相关试验VIP免费

乳腺癌的内分泌治疗乳腺癌的内分泌治疗乳癌内分泌治疗历史乳癌内分泌治疗历史18961896年年卵巢切除术治疗复发转移乳癌卵巢切除术治疗复发转移乳癌19221922年放疗卵巢去势年放疗卵巢去势19391939年雄性激素年雄性激素19441944年人工合成雌激素年人工合成雌激素19511951年孕激素年孕激素19531953年肾上腺切除和下丘脑切除年肾上腺切除和下丘脑切除19731973年三苯氧胺年三苯氧胺19811981年芳香化酶抑制剂年芳香化酶抑制剂19901990‘‘ss新一代的芳香化酶抑制剂新一代的芳香化酶抑制剂乳癌内分泌治疗药物乳癌内分泌治疗药物乙烯雌酚MPAMATAMAGZoladex雌激素孕激素抗雌激素芳香化酶抑制(失活)剂肾上腺皮质激素类Droloxifene兰他隆ExemestaneToremifeneArimidexFemara(Letrozole)三苯氧胺三苯氧胺TAMTAM（（Tamoxifen,Tamoxifen,他莫昔芬）他莫昔芬）目前最常用的非甾体类抗雌激素药目前最常用的非甾体类抗雌激素药复发转移乳癌的解救治疗复发转移乳癌的解救治疗乳癌术后预防复发转移的辅助治疗乳癌术后预防复发转移的辅助治疗高危健康妇女预防乳癌高危健康妇女预防乳癌TrialsFE5TamoxifenAdjuvantTamoxifenAdjuvantTherapyTherapyEarlyBreastCancerTriallistsEarlyBreastCancerTriallistsreporton55trialsin37,000reporton55trialsin37,000women.women.Lancet1998;Lancet1998;351:351:14511451TrialsFE6TamoxifenAdjuvantTherapyforTamoxifenAdjuvantTherapyforBreastCancerBreastCancer(I)(I)2211341751280102030405060%reduction1year2yrs5yrsoftherapyReductionsinriskinER+patientsRecurrenceMortalityTrialsFE7TamoxifenAdjuvantTherapyforTamoxifenAdjuvantTherapyforBreastCancerBreastCancer(II)(II)6-337215028-1001020304050%reductionERpoorERunknownER+veRiskreductionbyERstatus(5yrstherapy)RecurrenceMortalityTrialsFE8TamoxifenAdjuvantTherapyforTamoxifenAdjuvantTherapyforBreastCancerBreastCancer(III)(III)4532371154340102030405060%reduction<5050-59>60patientage(years)Riskreductionbyage,(ER+)RecurrenceMortalityTrialsFE9TamoxifenAdjuvantTherapyforTamoxifenAdjuvantTherapyforBreastCancerBreastCancer(IV)(IV)15791942020406080100120140160no.ofcasescontralat.b.c.EndometrialcancerIncidencein>20,000patientfollow-upyearsPlaceboTamoxifenAromataseAromataseAromataseAromataseAromataseAromataseAromataseAromataseTheRoleofAromataseinEstrogenTheRoleofAromataseinEstrogenBiosynthesisandTumorGrowthBiosynthesisandTumorGrowthAdrenalglandAdrenalglandPeripheraltissuesPeripheraltissuesPostmenopausalwomenPostmenopausalwomenTumorTumor=Estrogen=Androstenedione=Estrogen=AndrostenedioneReceptorReceptorEstroneEstradiolTestosteroneAromataseAromataseInactivatorsInactivatorsandandAromataseAromataseInhibitorsInhibitorsAndrostenedioneAnti-AromataseAgents:Anti-AromataseAgents:MechanismofActionMechanismofActionCholesterolCortisolProgesteroneAldosteronePregnenoloneGenerationGenerationFirstSecondThirdAnti-AromataseAgentsbyGenerationAnti-AromataseAgentsbyGenerationNonsteroidalNonsteroidalInhibitorsInhibitorsAminoglutethimideFadrozoleAnastrozoleLetrozoleSteroidalSteroidalInactivatorsInactivatorsTestolactoneFormestaneExemestane高选择性高选择性芳香化酶抑制剂芳香化酶抑制剂选择性选择性抑制芳香化酶抑制芳香化酶作用强度更强作用强度更强不良反应更轻不良反应更轻Femara(Letrozole)Femara(Letrozole)vsvsAminoglutethimide(AG)Aminoglutethimide(AG)PhaseIIITrialPhaseIIITrialFemara>AGFemara>AGClinicalBenefit(ClinicalBenefit(CR+PR+SD>=6CR+PR+SD>=6个月个月)%)%0%10%20%30%40%Femara0.5mgFemara2.5mgAG500mgP=0.03Femara>AGFemara>AGMedianDurationofMedianDurationofClinicalBenefit(months)ClinicalBenefit(months)0510152025Femara0.5mgFemara2.5...