乳腺癌辅助内分泌治疗相关试验

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1、乳腺癌的内分泌治疗乳癌内分泌治疗历史1896年卵巢切除术治疗复发转移乳癌1922年放疗卵巢去势1939年雄性激素1944年人工合成雌激素1951年孕激素1953年肾上腺切除和下丘脑切除1973年三苯氧胺1981年芳香化酶抑制剂1990‘s新一代的芳香化酶抑制剂乳癌内分泌治疗药物三苯氧胺TAM（Tamoxifen,他莫昔芬）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TrialsFE5TamoxifenAdjuvantTherapyEarlyBreastCance

2、rTriallistsreporton55trialsin37,000women.Lancet1998;351:1451TrialsFE6TamoxifenAdjuvantTherapyforBreastCancer(I)TrialsFE7TamoxifenAdjuvantTherapyforBreastCancer(II)TrialsFE8TamoxifenAdjuvantTherapyforBreastCancer(III)TrialsFE9TamoxifenAdjuvantTherapyforBreast

3、Cancer(IV)AromataseAromataseTheRoleofAromataseinEstrogenBiosynthesisandTumorGrowthAdrenalglandPeripheraltissuesPostmenopausalwomenTumor=Estrogen=AndrostenedioneReceptorEstroneEstradiolTestosteroneAromataseInactivatorsandAromataseInhibitorsAndrostenedioneAnti-A

4、romataseAgents:MechanismofActionCholesterolCortisolProgesteroneAldosteronePregnenoloneGenerationFirstSecondThirdAnti-AromataseAgentsbyGenerationNonsteroidalInhibitorsAminoglutethimideFadrozoleAnastrozoleLetrozoleSteroidalInactivatorsTestolactoneFormestaneExem

5、estane高选择性芳香化酶抑制剂选择性抑制芳香化酶作用强度更强不良反应更轻Femara(Letrozole)vsAminoglutethimide(AG)PhaseIIITrialFemara>AGClinicalBenefit(CR+PR+SD>=6个月)%P=0.03Femara>AGMedianDurationofClinicalBenefit(months)P=0.0314个月21个月AdexProdFEAnastrozole(Arimdex)vsMegestrolAcetateinAdvanced

6、BreastCancerPhaseIIITrialsSurvivalDataAnastrozole/MAMediantimetodeath(months)2yearsurvivalrate(%)P<0.05Femara®(letrozole)vsTamoxifenasFirst-LineTherapy025Cross-OverDesign916MBC458Letrozole458TamoxifenProgressionCross-OverProgressionSurvivalFollow-upLetrozoleT

7、amoxifenLetrozole>TamoxifenResponseRate(%)P<0.001P<0.001TTP:Kaplan-MeierCurveLetrozoleTamoxifen0.00.10.20.30.40.50.60.70.80.91.003691215182124MonthsProportionofpatientswithoutprogressionFemara®(letrozole)vsTamoxifenasPre-OperativeTherapy024DesignDouble-blind

8、,double-dummy,randomized,parallelgroup,multicenter(55centersin16countries),phaseIIb/IIItrialFemara®(letrozole)2.5mgo.d.Tamoxifen20mgo.d.SurgeryFollow-uptherapy(inves