乳腺癌内分泌治疗.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,乳腺癌内分泌治疗进展,内分泌治疗,抗雌激素受体,:,三苯氧胺,法乐通,(,托瑞米芬,),氟维司群,芳香化酶抑制剂,:,阿那曲唑,来曲唑,依西美坦,甲地孕酮,甲羟孕酮,诺雷得,其他,乳腺癌早期复发高峰,0,5,10,15,20,25,0.5,1.5,2.5,3.5,4.5,5.5,6.5,7.5,8.5,9.5,10.5,Year,Hazard of recurrence by yearly,interval,Total,Node 0,Node 1-3,Node(4+),Tumour size(3cm),ER+,ER-,Premen,Postmen,无辅助治疗患者的早期复发风险,(3 yrs),Early Breast Cancer Trialists Collaborative Group.,Lancet,.1998;351:1451.Update of Houghton.,J Clin Oncol,.2005;23(16S):24s.Abstract 582.,Saphner et al.,J Clin Oncol,.,14:2738-2746,1996,乳腺癌早期复发高峰,0,5,10,15,20,25,0.5,1.5,2.5,3.5,4.5,5.5,6.5,7.5,8.5,9.5,10.5,Year,Hazard of recurrence by yearly,interval,ER+,ER-,Premen,Postmen,无辅助治疗患者的早期复发风险,(3 yrs),Early Breast Cancer Trialists Collaborative Group.,Lancet,.1998;351:1451.Update of Houghton.,J Clin Oncol,.2005;23(16S):24s.Abstract 582.,Saphner et al.,J Clin Oncol,.,14:2738-2746,1996,内分泌治疗获益,内分泌治疗的预测因素,高,中,低,缺失,激素敏感,内分泌治疗改善,DFS,和,OS,激素敏感不确定,单独内分泌治疗可能不够,激素不敏感,最好化疗,ER,定量，,PR,表达低,/,缺失，,HER2,过表达，增生指标增加，肿瘤负荷大,内分泌治疗的受益,早期乳腺癌,-,激素反应性,(,激素依赖性,),低危,:,内分泌治疗,中危,:,化疗,内分泌治疗,(,放疗,),HER-2+:,加,Hercetin,高危,:,化疗,内分泌治疗,(,放疗,),HER-2+:,加,Hercetin,低危,:LN-;G1,级,Her-2-;35,岁,中危,:LN+(1-3);G2-3,级,PT2cm;Her-2-;60,岁,年令,12,月,;FSH,、,E2,绝经范围,无化疗、内分泌治疗,.,年令,TAM,客观反应率,保乳比例,低,ER,表达,Her-2,过表达,AI TAM,远处转移,高危：,N+,2008,年,初始？,序贯？,AI,安慰剂,DFS,远处转移,对侧,BC,N+,死亡率,FTAM,TTP,ORR,临床受益率,生存优势,FMA,AG,FA,手术,术前治疗,初始,AI,辅助治疗进一步降低早期复发高峰,0.5,1.0,1.5,2.0,2.5,3.0,0,1,2,3,4,5,6,Follow-up time(years),AI,TAM,0,年复发率,(%),5,年,Tam,5,年,AI,2,年,Tam,序贯,AI,5,年,Tam,序贯,AI,复发丧失的生命年(%,),随访年份,0,5,10,15,0,2,4,6,8,10,Cuzick J et al.Br J Cancer 2006,病例分析,病例分析,浸润性乳腺癌内分泌治疗,抗雌激素受体,:,三苯氧胺,法乐通,(,托瑞米芬,),氟维司群,芳香化酶抑制剂,:,阿那曲唑,来曲唑,依西美坦,甲地孕酮,甲羟孕酮,诺雷得,原则,:,TAMAI,AI,孕激素或氟维司群,未用过抗雌激素受体治疗或辅助治疗,1,年失败者,试用,TAM.,ER+,绝经前,卵巢功能抑制,绝经后处理,.,芳香化酶抑制剂辅助治疗的安全性问题,AI,的不良反应,一般不良反应,热潮红、妇科症状、关节症状、血栓栓塞,骨质丢失,血脂影响,心血管系统、心脏,热潮红：,AI,辅助治疗,Refs.:ATAC Trialists Group.Lancet.2005;365:60;Thrlimann et al.www.ibcsg.org,Thurlimann et al.,N Engl J Med.,2005;353:2747;,Coates.ESMO 2006.At:http:/www.ibcsg.org/public/documents/pdf/trial_18-98_big1-98/BIG1-98_ESMO_2006.pdf;,Coombes et al.,J Clin Oncol.,2006;24(18S):933s.Abstract LBA527,Jakesz et al.,Breast Cancer Res Treat,.2004;88:57.Abstract 2;Goss et al.,J Natl Cancer Inst.,2005;97:1262.,研究,中位跟踪（月）,AI,对照药物,AI vs,对照药物,(%),P,ATAC,68,ANA,TAM,36 vs 41,0.0001,BIG 1-98,26,LET,TAM,34 vs 38,0.001,51,32.8 vs 37.4,IES,31,EXEM,TAM,42 vs 40,0.28,ARNO,28,ANA,TAM,MA-17,30,LET,安慰剂,58 vs 54,0.003,关节痛：,AI,辅助治疗,Refs.:ATAC Trialists Group.Lancet.2005;365:60;Thrlimann et al.www.ibcsg.org,Thurlimann et al.,N Engl J Med.,2005;353:2747;,Coates.ESMO 2006.At:http:/www.ibcsg.org/public/documents/pdf/trial_18-98_big1-98/BIG1-98_ESMO_2006.pdf;,Coombes et al.,J Clin Oncol.,2006;24(18S):933s.Abstract LBA527,Jakesz et al.,Breast Cancer Res Treat,.2004;88:57.Abstract 2;Goss et al.,J Natl Cancer Inst.,2005;97:1262.,研究,中位跟踪（月）,AI,对照药物,AI vs,对照药物,(%),P,ATAC,68,ANA,TAM,36 vs 29,0.0001,BIG 1-98,26,51,LET,TAM,20 vs 1220 vs 13.5,0.001,IES,55,EXEM,TAM,21 vs 15,0.001,ARNO,28,ANA,TAM,MA-17,30,LET,安慰剂,25 vs 21,0.001,妇科症状,/,子宫内膜癌：,AI,辅助治疗,51-mo monotherapy update,Refs.:ATAC Trialists Group.Lancet.2005;365:60;Thrlimann et al.www.ibcsg.org,Thurlimann et al.,N Engl J Med.,2005;353:2747;,Coates.ESMO 2006.At:http:/www.ibcsg.org/public/documents/pdf/trial_18-98_big1-98/BIG1-98_ESMO_2006.pdf;,Coombes et al.,J Clin Oncol.,2006;24(18S):933s.Abstract LBA527,Jakesz et al.,Breast Cancer Res Treat,.2004;88:57.Abstract 2;Goss et al.,J Natl Cancer Inst.,2005;97:1262.,研究,中位跟踪（月）,AI,对照药物,事件,AI vs,对照药物,(%),P,ATAC,68,ANA,TAM,阴道排液,3.5 vs 13.2,0.0001,阴道出血,5.4 vs 10.2,0.0001,子宫内膜癌,0.2 vs 0.8,0.02,BIG 1-98,26,LET,TAM,阴道出血,3.3 vs 6.6(3.8 vs 8.3,),0.001,子宫内膜活检,1.9 vs 7.2,NI,子宫内膜癌,0.2 vs 0.4,NI,IES,55,EXE,TAM,严重的妇科症状,6.4 vs 9.8,0.01,阴道出血,4.8 vs 7.1,0.01,子宫内膜癌,0.4 vs 0.7,NS,ARNO,28,ANA,TAM,MA-17,30,LET,安慰剂,阴道出血,6 vs 8,0.005,血栓栓塞：,AI,辅助治疗,Refs.:ATAC Trialists Group.Lancet.2005;365:60;Thrlimann et al.www.ibcsg.org,Thurlimann et al.,N Engl J Med.,2005;353:2747;,Coates.ESMO 2006.At:http:/www.ibcsg.org/public/documents/pdf/trial_18-98_big1-98/BIG1-98_ESMO_2006.pdf;,Coombes et al.,J Clin Oncol.,2006;24(18S):933s.Abstract LBA527,Jakesz et al.,Breast Cancer Res Treat,.2004;88:57.Abstract 2;Goss et al.,J Natl Cancer Inst.,2005;97:1262.,研究,中位跟踪（月）,AI,对照药物,事件,AI vs,对照药物,(%),P,ATAC,68,ANA,TAM,静脉血栓 深静脉血,2.8 vs 4.51.6 vs 2.4,0.0004 0.02,BIG 1-98,2,6,51,LET,TAM,血栓栓塞,1.0 vs 2.42.0 vs.3.8,0.001,IES,55,EXEM,TAM,血栓栓塞,1.9 vs.3.1,ULN,300,ULN,7.75,300,400,7.75,10.34,400,500,10.34,12.92,500,12.92,mg/dL,mmol/L,Thurlimann B et al.N Engl J Med 2005;353(26):2747-57.,*To convert mmol/L to mg/dL,multiply by 39.,Perez.,EJC Supplements,.2006;4:16.,Months,Let 3209,Tam 3226,2606,2599,2660,2671,2546,2588,2264,2255,1716,1679,1253,1226,863,831,698,695,527,519,6,25,BIG1-98,试验中血胆固醇距基线的变化,在来曲唑组血血胆固醇距基线保持稳定,在他莫昔芬组血胆固醇距基线下降