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单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,乳腺癌辅助化疗蒽环类药物基石地位是否动摇,蒽环类药物在早期乳腺癌中的应用：,ABC,试验,Anthracyclines in Early Breast Cancer: The ABC TrialsUSOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology),JOURNAL OF CLINICAL,IF,：,2016 ASCO,内容,蒽环类基石地位,结论,HER-2(-),蒽环类应用,思考,五,HER-2(+),蒽环类应用,三,一,四,二,蒽环类开启乳腺癌化疗的新篇章,蒽环类首次分子合成于,60,年代,蒽环类药物,作用与,DNA,和,RNA,，,属于嵌入型,TOP2,抑制剂,蒽环类药物主要作用机制之一，是它与,DNA,结合，通过抑制,TOP2,使,DNA-TOP2,复合物处于稳定状态，促进,DNA,双链断裂。,1975,年，蒽环类应用于乳腺癌的治疗,蒽环方案超越,CMF,Early Breast Cancer Trialists Collaborative Group (EBCTCG). Lancet 2012; 379: 43244.,复发率,全因死亡率,0,5,10,年,年,4,AC =,6,CMF,TAM,(NSABP B-15, B-23),E,-,CMF CMF,(NEAT/BR9601),CEF CMF,(,MA.5, ICCG,),足剂量足周期是蒽环疗效的保证,A,60,C= A,75,C = A,90,C,(,CALGB 9741,),E,100,C,E,60,C,(,比利时,III,期,),CAF,高剂量, CAF,低剂量,（,CALGB 8541,）,FEC,足剂量组疗程, FEC,低剂量短疗程,（,FASG 01, FASG 05,）,ABC,辅助性试验由,USOR,及,NSABP,联合进行，是三个研究的联合分析。,目的：在,TC,优于,AC,的证据面前，,探讨,TC,方案在,IDFS,是否非劣效于,TaxAC,方案。,ABC,研究背景,JOURNAL OF CLINICAL ONCOLOGY VOLUME 35 NUMBER 23 AUGUST 10, 2017,A,: 60mg/m,2,d1,C,: 600mg/m,2,d1,q34,C,: 600mg/m,2,d1,q34,D,: 75mg/m,2,d1,53%LN,阳性,EBC,(n=1016),US9735,A:,多柔比星,C:,环磷酰胺,P:,紫杉醇,T/,D:,多西他赛,入组及治疗情况,Her-2(-),JOURNAL OF CLINICAL ONCOLOGY VOLUME 35 NUMBER 23 AUGUST 10, 2017,T1-3 N+,N-,ER,、,PR,（,-,）,T,2cm,T1c ER,、,PR,（,+,） 组 织学,级,/Oncotype DX,31(stage 1) DX,25(stage 2,、,3),TC6 q3w,D 75mg/m2+C 600mg/m2,N=2094,TaxAC q3W,TAC,D 75mg/m2+A 50mg/m2+C 600mg/m2,AC T,AC q3w 4 P 80mg/m2 qw12/P 175mg/m2 q2w 4,R,主要研究终点,IDFS,次要研究终点,RFI,DFS-DCIS,OS,毒性,假设,HR,，定义为,TC,对比,TaxAC,劣效。,中期分析：在总人群中，,TaxAC,可显著提高侵袭性无病生存率,随机取样后年份,侵袭性无病生存率,%,治疗,N,事件,4,年,IDFS,JOURNAL OF CLINICAL ONCOLOGY VOLUME 35 NUMBER 23 AUGUST 10, 2017,分层分析,TC,更好,TaxAC,更好,JOURNAL OF CLINICAL ONCOLOGY VOLUME 35 NUMBER 23 AUGUST 10, 2017,HR,Hormone,-,+,Nodes,0,1-3,4-9,10,Overall,0.5 1.0 1.5 2.0 2.5 3.0,HR,、淋巴结联合分析,TC,更好,TaxAC,更好,JOURNAL OF CLINICAL ONCOLOGY VOLUME 35 NUMBER 23 AUGUST 10, 2017,HR,1.31,1.58,1.34,0.69,1.14,1.46,1.23,WSG Plan B,试验,：,高风险,pN0,（,T2-4, G2-3, 35,岁,高,PA/PAI-1,）或,pN+HER2-EBC,（,N=,2449,）,R,TC,6,辅助化疗,（,n=1222,）,EC4-D4,辅助化疗（,n=1227,）,41%,是,pN+,42%,为,G3,18%HR,阴性,2017 ASCO Abstract 504.,5,年,DFS,为,89.9%88.1%-91.7%,和,%,5,年,OS,为,94.7%93.4%-96.1%,和,%,ABC,与,Plan B,基线比较,激素受体状态,ABC,Plan B,ER,或,PR,（,+,）,69%,81%,ER,及,PR,（,-,）,31%,19%,LN +,0,41%,59%,1-3,44%,35%,4-9,12%,5%,10+,4%,2%,病理分级,低,10%,64%,中,37%,高,51%,36%,未知,2%,HER-2,阳性患者？,HER-2,阳性患者,San Antonio Breast Cancer Symposium 2015,HER,阳性（,FISH,）淋巴结阳性和高危淋巴结阴性早期乳腺癌,N=3222,AC-T,AC-TH,TCH,AC4,60/600mg/m2,多西紫杉醇,4,100mg/m2,1,年赫赛汀治疗,多西紫杉醇,6/,卡铂,75mg/m2 AUC 6,1,年赫赛汀治疗,BCIRG 006,研究设计,Gennari A, et al. J Natl Cancer Inst. 2008;100:14-20.,汇总分析显示：,Her2,阳性早期乳腺癌从蒽环类方案中显著获益,Test for interaction chi,2,= 13.7;,P, .001,非蒽环类更好,NCIC MA-5,Overall,DBCCG-89-D,Milan,Brussels,NSABP B15,NSABP B11,研究,HR,95% CI,蒽环类更好,0.6,1.0,2.0,5.0,0.4,P, .0001,P,= 1.0,0.9,Total,P,= .01,HER2,阳性,0.600.96,0.841.02,0.651.35,0.831.22,0.750.79,0.520.91,0.90,0.711.00,0.44-0.820.75-1.23,0.65-1.080.86-1.20,0.34-1.270.93-1.97,0.46-1.490.91-1.64,0.53-1.060.60-1.05,0.34-0.800.71-1.17,0.82-0.98,0.61-0.830.90-1.11,HER2,阴性,蒽环,vs.,非蒽环与,HER2,状态,(OS),专家共识,HER-2,（,-,）：,ER,、,PR,阴性、,T1b,以上患者，及淋巴结阳性患者，方案应包含蒽环类和紫衫类。,HER-2,（,+,）：,T2,以上及淋巴结阳性患者应蒽环序贯紫衫类。,结论,1,、,Her-2,（,-,）乳癌患者辅助治疗中，低危患者蒽环类药物有无必要尚有争议；对于高危患者，蒽环类药物仍然不可或缺。,2,、,Her-2,（,+,）乳癌患者，,AC-TH,方案既往的循证医学数据更为充分，蒽环类药物仍然重要。,思考与探讨,1,、脂质体阿霉素可作为复发转移性乳腺癌的治疗用药，但辅助治疗中证据尚少。,2,、如何应用分子生物学指标筛选蒽环类药物的优势人群。,谢谢,
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