早期乳腺癌术后辅助化疗课件.ppt

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,*,*,文档仅供参考，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。,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,文档仅供参考，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。,目 录,乳腺癌,TNM,分期与分子分型,2013 NCCN,术后辅助化疗更新及相关理论,乳腺癌化疗药物发展史及其毒副反应,乳腺癌治疗流程图,乳腺癌疾病分类（根据,NCCN,指南）,非浸润性癌乳腺癌,1,.小叶原位癌,2,.导管原位癌,3.,伴导管原位癌的,Pages,病,浸润癌乳腺癌,1,浸润小叶癌,2,浸润导管癌,特殊型：,分叶状肿瘤；,Pagets,病；炎性乳腺癌,NCCN Clinical Practice Guidelines in Oncology,TM,乳腺癌临床实践指南（中国版）,2011,年 第一版（源自英文版,V.2.2011,）,www.nccn.org,ER+,和,/,或,PR+,ER-/PR-,L,uminal B,：,-55%,ER+,和,/,或,PR+&HER2+,ER+,和,/,或,PR+&,HER2-&Ki6714%,化疗,靶向药物,内分泌治疗,预后较好,HER2,过表达,：,-15%,ER-/PR-&HER2+,主张化疗,+,靶向药物联合,预后较差,HER2+,Luminal A,：,15%,ER+,和,/,或,PR+&HER2-&Ki6714%,没有高危因素倡导直接内分泌治疗,对化疗的敏感性低，但预后好,三阴性,：,15%,ER-/PR-&HER2-,对化疗敏感性高，容易达到,pCR,但预后差，容易复发,HER2-,乳腺癌分子分型,Katrina R.et al.Descriptive Analysis of Estrogen Receptor(ER)-Negative,Progesterone Receptor(PR)-Negative,and HER2-Negative Invasive Breast Cancer,the Socalled Triple-Negative Phenotype.A Population-Based Study From the California Cancer Registry.CANCER May 1,2007/Volume 109/Number 9.1721-8,目 录,乳腺癌,TNM,分期与分子分型,2013 NCCN,术后辅助化疗更新及相关理论,乳腺癌化疗药物发展史及其毒副反应,乳腺癌治疗流程图,早期乳腺癌的常用治疗手段,辅助治疗,新辅助,内分泌,靶向,手术,化疗,放疗,辅助化疗,被定义为在手术后给予系统的细胞毒化疗以,杀死或抑制临床无法检测的微转移。,S.Aebi,et al.Primary breast cancer:ESMO Clinical Practice Guidelines for diagnosis,treatment and follow-up.Ann Oncol.2011 Sep;22 Suppl 6:vi12-24.,HER2+,ER+,或,PR+,有放疗指证,有化疗指证,治疗决策树,手术,可手术乳腺癌（,I-III,期）,局部晚期病人,：,IIIA,(,除,T3,N1,M0,),IIIB-IIIC,I-IIIA,(,仅,T3,N1,M0,),选择仅含蒽环类方案,选择仅含紫杉类方案,选择同时含紫杉类和蒽环类方案*,根据分期（肿瘤大小和淋巴结转移）、分子分型、年龄等情况评估复发风险（,2007,年,St.Gallen,制定的复发风险等级划分权威性和影响力很大）,低危患者,IIB,以下,淋巴结阴性,中,高危人群,IIB,以上,淋巴结阳性,（,3,个转移）,年轻,（,1CM,、有高危因素,需完成剩余疗程,疾病诊断,疾病治疗,类别选择,原位癌,浸润性癌中分期很早,(I,期,),没有高危因素,(,没有淋巴转移、年龄,70,岁,),的,Luminal A,不需要术后辅助化疗,目 录,乳腺癌,TNM,分期与分子分型,2013 NCCN,术后辅助化疗更新及相关理论,乳腺癌化疗药物发展史及其毒副反应,乳腺癌治疗流程图,1970,s,1980,s,1990,s,2000,s,乳腺癌化疗药物的进展,非蒽环类的联合化疗,CMF,蒽环类联合化疗,A,C,F,A,C,A/E,CMF,F,E,C,C,E,F,紫杉类(,Paclitaxel/Docetaxel,),序贯:,A,P,C,or,AC,P(T),联合:,T,C,T,AC,靶向药物,与化疗策略结合,AC,PH(TH),T,C,H,CMF方案,无化疗,1970,4.2%获益,蒽环类方案,1980,4.3%获益,紫杉类方案,2000,5.1%获益,辅助化疗在过去,40年对患者总生存的改善情况,化疗+曲妥珠单抗,6%获益,2006,化疗持续地改善了早期乳腺癌的预后,在早期乳腺癌的治疗中扮演了非常重要的角色,Peto R.EBCTCG Meta-analysis 2005-2006.SABCS 2007,目 录,乳腺癌,TNM,分期与分子分型,2013 NCCN,术后辅助化疗更新及相关理论,乳腺癌化疗药物发展史及其毒副反应,乳腺癌治疗流程图,2012,版乳腺癌,NCCN,指南,2013,版乳腺癌,NCCN,指南,全身治疗,对于,激素受体阳性、,HER-2,阳性的乳腺癌患者,辅助内分泌治疗辅助化疗曲妥珠单抗,辅助内分泌治疗或辅助化疗曲妥珠单抗序贯内分泌治疗,激素受体阳性、,HER-2,阴性的乳腺癌患者,“辅助,内分泌治,疗”,及“辅助化疗”为,“,2B,类推荐”,“辅助,内分泌治,疗”,及“辅助化疗”为,“,2A,类推荐”,术前辅助化疗,-,增加“,如术前未完成全部化疗，术后应,完成,全部化疗；如雌激素和,/,或孕激素受体阳性，需加用内分泌治疗（首先进行化疗，随后进行内分泌治疗）,辅助化疗,TAC,方案,为,优选方案,TAC,方案,为其他,方案,AC,（多柔比星,/,环磷酰胺）紫杉醇周疗,剂量密集,AC,（多柔比星,/,环磷酰胺）紫杉醇周疗,-,增加“,FAC,T,（氟尿嘧啶,/,多柔比星,/,环磷酰胺紫杉醇周疗）方案,2013,版乳腺癌,NCCN,指南更新要点,2013,版乳腺癌,NCCN,指南更新要点,全身治疗,激素受体阳性、,HER-2,阴性的乳腺癌患者的全身辅助治疗,对于,肿瘤直径,0.5cm,的低,高复发评分的患者，“辅助,内分泌治,疗”,及“辅助化疗”均,由“,2B,类推荐”改为“,2A,类推荐,”,激素受体阳性、,HER-2,阳性的乳腺癌患者的全身辅助治疗,对于肿瘤直径,0.5cm,或可行微创手术切除且,pN1mi,的患者，治疗由,2012,版指南中的,“辅助内分泌治疗辅助化疗曲妥珠单抗”改为,2013,版指南的,“辅助内分泌治疗或辅助化疗曲妥珠单抗序贯内分泌治疗”,2013,版乳腺癌,NCCN,指南更新要点,术前辅助化疗,浸润性乳腺癌的“术前辅助化疗”部分,与,2012,版指南相比，,2013,版指南“术前化疗”中的,“辅助治疗”,部分,增加,一点：,“如术前未完成全部化疗，术后应,完成,全部化疗；如雌激素和,/,或孕激素受体阳性，需加用内分泌治疗（首先进行化疗，随后进行内分泌治疗）,”,2013,版乳腺癌,NCCN,指南更新要点,辅助化疗,浸润性乳腺癌的“辅助化疗”部分,将“,TAC,（多西他赛,/,多柔比星,/,环磷酰胺）”方案由,2012,版指南的,“优选方案”改为,2013,版指南的,“其他方案”,优选方案中将,2012,版指南的,“,AC,（多柔比星,/,环磷酰胺）紫杉醇周疗”改为,2013,版指南的,“剂量密集,AC,（多柔比星,/,环磷酰胺）紫杉醇周疗”,2013,版指南中,增加“,FAC,T,（氟尿嘧啶,/,多柔比星,/,环磷酰胺紫杉醇周疗）方案,同样的药物组合,如何达到最大效能,?,序贯,vs.,联合，哪种给药方式更好,？,剂量密集,vs.,传统,3,周，哪种给药方案更优？,BCIRG001,多西他赛,75 mg/m,2,多柔比星,50 mg/m,2,环磷酰胺,500 mg/m,2,5-,氟尿嘧啶,500 mg/m,2,多柔比星,50 mg/m,2,环磷酰胺,500 mg/m,2,仅在出现一次粒缺性发热或感染事件后使用环丙沙星预防和治疗,F,A,C,T,A,C,R,每周期化疗前,1,天给予地塞米松,8 mg bid,连续,3,天,预先给予环丙沙星,500mg bid,每周期的第,5-14,天,每,3,周,6,个周期,淋巴结阳性,乳腺癌患者,N=1480,1997.6-1999.6,N Engl J Med.2005 Jun2;352(22):2302-13,主要终点：无病生存期,(DFS),次级终点：总生存期,(OS),、毒性,治疗中出现粒缺性发热或感染，立即给予,G-CSF,（来格斯亭,150ug/m,2,.,天，或菲格斯亭,5ug/kg.,天），,并在之后的每个周期的第,4,11,天预防使用,激素受体阳性患者在化疗结束后使用他莫昔芬治疗,5,年,TAC:76%,FAC:69%,DFS at a Median 10-year Follow-up(ITT),Number at Risk,TAC,745,737,710,678,659,639,617,596,583,562,551,541,530,519,508,491,478,463,444,418,387,FAC,746,730,699,659,618,584,558,541,523,510,499,484,471,453,437,429,414,392,378,351,333,Disease-free survival probability,0.00,0.20,0.40,0.60,0.80,1.00,Disease-free survival time(months),0,6,12,18,24,30,36,42,48,54,60,66,72,78,84,90,96,102,108,114,120,HR=0.7295%CI:0.590.88Log-rank P=0.001,HR=0.8095%CI:0.680.93Log-rank P=0.0043,BCIRG 001,结果,Lancet Oncol.2013;14:72-80,OS at a Median 10-year Follow-up(ITT),429 deaths:,188 TAC;241 FAC,Number at Risk,TAC,745,742,732,718,704,693,677,661,650,645,635,622,612,603,594,584,571,563,547,524,495,FAC,746,740,731,724,704,684,657,642,625,608,591,581,573,557,546,532,517,501,482,460,443,Overall survival probability,0.00,0.20,0.40,0.60,0.80,1.00,0,6,12,18,24,30,36,42,48,54,60,66,72,78,84,90,96,102,108,114,120,TAC:87%,FAC:81%,HR=0.7095%CI:0.530.91Log-rank P=0.008,HR=0.7495%CI:0.610.90Log-rank P=0.002,Survival time(months),BCIRG 001,结果,Lancet Oncol.2013;14:72-80,BCIRG001,三年随访结果：对于,4,个淋巴结阳性的乳腺癌患者，,TAC,方案不能提供显著更优的,DFS,获益,无病生存期,(,月,),无病生存率,(%),Martin M,et L.SABCS 2003(abs 43).,N Engl J Med.2005 Jun2;352(22):2302-13,BCIRG001,亚组分析,3,年,DFS,：,TAC,方案对,HER2+/,三阴性,/Luminal A,型，无治疗优势,三阴性,HER2+,Luminal B,Luminal A,Hugh J,et al.J Clin Oncol 2009;27:1168-1176,BCIRG 001,研究十年随访结果,&,亚组分析报告：,DFS,Mackey R,Martin M,Pienkowski T,et al.Adjuvant docetaxel,doxorubicin,and cyclophosphamide in node-positive breast cancer:10-year follow-up of the phase 3 randomised BCIRG 001 trial.,Lancet Oncol 2013;14:7280.,BCIRG 001,研究十年随访结果,&,亚组分析报告：,OS,BCIRG 001,：,TAC,方案血液学毒性发生率显著更高,毒性,TAC,组,(n=744),FAC,组,(n=736),P,值,P,值,所有患者,3,级及以上毒性,所有患者,3,级及以上毒性,所有患者,3,级及以上毒性,贫血,所有患者,91.5,4.3,71.7,1.6,0.001,0.003,需输血治疗患者,4.6,-,1.5,-,0.001,-,血小板减少,39.4,2.0,27.7,1.2,0.001,0.23,中性粒细胞减少性发热,本研究定义*,24.7,-,2.5,-,0.001,-,NCI,CTC(2.0,版,),定义*,28.8,-,4.4,-,0.001,-,中性粒细胞减少性感染,本研究定义,#,12.1,-,6.3,-,0.001,-,NCI,CTC(2.0,版,),定义,#,20.4,-,10.8,-,20%,58(17%),41(15%),0.632,0.660,LVEF,低于正常下限,41(12%),27(10%),0.492,0.520,Martin M,Pienkowski T,Mackey J,et al.Adjuvant Docetaxel for Node-Positive Breast Cancer.N Engl J Med 2005;352:2302-13.,Mackey R,Martin M,Pienkowski T,et al.Adjuvant docetaxel,doxorubicin,and cyclophosphamide in node-positive breast cancer:10-year follow-up of the phase 3 randomised BCIRG 001 trial.,Lancet Oncol 2013;14:7280.,BCIRG001,结论,TAC,方案对比,FAC,方案,有更好的生存获益，但,对,4,个以上淋巴结阳性的高危,患者，,DFS,和,OS,均无治疗优势,（无统计学差异），,对,三阴性,、,HER2+,、,Luminal A,型,患者，其,OS,均,无治疗,优势,（无统计学差异）,TAC,方案化疗毒性反应,严重，尤以,血液学毒性,为甚，,增加患者,感染和死亡的风险，同时增加治疗成本,十年,随访结果显示，,TAC,方案,增加远期慢性,心衰的发生率,，可能由于多西他赛易引起体液潴留，加重心脏负担有关,仅供内部使用,AC-T,TAC,治疗指数疗效,/,毒副反应,BCIRG005,：多西他赛序贯化疗,vs.,联合化疗,可手术切除、淋巴结阳性的,HER2,阴性乳腺癌患者,（,N=3298,）,R,TAC,辅助化疗,多柔比星,50 mg/m,2,环磷酰胺,500 mg/m,2,每,3,周,6,个周期,多西他赛,75 mg/m,2,（,n=1649,）,ACT,辅助化疗,多柔比星,60 mg/m,2,环磷酰胺,600 mg/m,2,多西他赛,100 mg/m,2,每,3,周,4,个周期,（,n=1649,）,每,3,周,4,个周期,分层：中心；腋窝淋巴结数目（,13 vs.4,）；激素受体状态（,ER,和,/,或,PR,阳性,vs.,阴性）。,主要终点：,DFS,；,次要终点：,OS,、安全性,Eiermann W,Pienkowski T,Crown J,Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal,node-positive breast cancer:BCIRG-005 trial.,J Clin Oncol.2011 Oct 10;29(29):3877-84.,BCIRG005,：序贯方案与联合方案的,DFS,获益相当,无病生存期,(,月,),无病生存率,Eiermann W,Pienkowski T,Crown J,Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal,node-positive breast cancer:BCIRG-005 trial.,J Clin Oncol.2011 Oct 10;29(29):3877-84.,BCIRG005,：序贯方案与联合方案的,OS,获益相当,总生存率,总生存期,(,月,),Eiermann W,Pienkowski T,Crown J,Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal,node-positive breast cancer:BCIRG-005 trial.,J Clin Oncol.2011 Oct 10;29(29):3877-84.,BCIRG005,：序贯方案与联合方案相比,中性粒细胞减少性发热等血液学毒性发生率更低,7.7,17.4,2.0,2.9,1.3,2.5,P,序贯方案的,治疗指数,优于联合方案,同样的药物组合,如何达到最大效能,?,剂量,密集,vs.,传统,3,周，哪种给药方案更优？,Norton-simon,剂量密集学说：与“正常”给药周期相比，剂量密集化疗能杀死更多的肿瘤细胞,1,10,2,10,4,10,6,10,8,10,10,10,12,1,0,7,6,5,4,3,2,时间,(,月,),肿瘤细胞数,剂量密集假说：通过缩短传统化疗间隔时间，给药的时间更频繁，而给药的剂量不变，以达到更大程度的细胞杀伤作用。,利用这种方法有两个好处：,由于缩短化疗间隔时间，这样在化疗间歇期可使更少的肿瘤细胞重新进入再生长，也可减少对化疗药耐药的恶性细胞的出现。,通过缩短给药间隔时间，可以使肿瘤细胞更频繁地曝露在细胞毒药物中，使细胞内的生长信号受到更大程度的影响，促进细胞凋亡和抗血管生成，从而达到最大程度的细胞杀伤作用。,陈强,杨建伟,.,剂量密集疗法及其在乳腺癌治疗中的应用,.,药品评价,.2005;2(4):251-254.,Monica Fornier and Larry Norton.Dose-dense adjuvant chemotherapy for primary breast cancer.Breast Cancer Research.2005;7():64-69.,INT C9741/CALGB 9741,：研究设计,Citron ML,Berry DA,Cirrincione.C,et al.Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer:First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741.J Clin Oncol.2003;21:1431-1439,淋巴结阳性的,原发性乳腺癌患者,（,N=2005,）,R,方案,I,：,A q3w 4P q3w 4C q3w 4,多柔比星,60mg/m,2,紫杉醇,175 mg/m,2,环磷酰胺,600mg/m,2,剂量密集化疗组加用非格司亭,5ug/kg,，,d3d10,。,主要终点：,DFS,次要终点：,OS,方案,II,：,A q2w 4P q2w 4C q2w 4,方案,III,：,AC q3w 4P q3w 4,方案,IV,：,AC q2w 4P q2w 4,INT C9741/CALGB 9741,：紫杉醇剂量密集化疗方案,较常规,3,周方案显著降低复发风险达,26%,INT C9741,/CALGB 9741,Citron ML,Berry DA,Cirrincione.C,et al.Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer:First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741.J Clin Oncol.2003;21:1431-1439,0,0.2,0.4,0.6,0.8,1,0,1,2,3,4,无病生存期,(,年,),无病生存率,q 2 wks,（,n=988,）,q 3 wks,（,n=985,）,RR,：,0.74;P=0.010,中位随访,36,个月,紫杉醇剂量密集方案的获益不受肿瘤大小、累及的淋巴结数量、患者的激素受体以及绝经状态影响,INT C9741/CALGB 9741,：紫杉醇剂量密集化疗方案,较常规,3,周方案显著降低死亡风险达,31%,INT C9741,/CALGB 9741,Citron ML,Berry DA,Cirrincione.C,et al.Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer:First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741.J Clin Oncol.2003;21:1431-1439,q 2 wks,（,n=988,）,q 3 wks,（,n=985,）,RR,：,0.69;P=0.013,0,0.2,0.4,0.6,0.8,1,0,1,2,3,4,总生存期,(,年,),总生存率,中位随访,36,个月,紫杉醇剂量密集方案的获益不受肿瘤大小、累及的淋巴结数量、患者的激素受体以及绝经状态影响,INT C9741/CALGB 9741,：,G-CSF,支持下，紫杉醇剂量密集方案的严重中性粒细胞减少发生率更低,INT C9741,/CALGB 9741,Citron ML,Berry DA,Cirrincione.C,et al.Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer:First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741.J Clin Oncol.2003;21:1431-1439,6%,33%,发生率,(%),4,级中性粒细胞减少,P0.0001,紫杉醇密集和,TAC,方案哪个更好呢？,NSABP B-38,：研究设计,可手术的腋窝淋巴结阳性乳腺癌患者,（,N=4894),R,DD ACP,辅助化疗,多柔比星,60mg/m,2,环磷酰胺,600mg/m,2,紫杉醇,175 mg/m,2,每,2,周,4,（,n=1634,）,每,2,周,4,DD ACPG,辅助化疗,多柔比星,60mg/m,2,环磷酰胺,600mg/m,2,紫杉醇,175 mg/m,2,吉西他滨,2000 mg/m,2,（,n=1630,）,每,2,周,4,每,2,周,4,TAC,辅助化疗,多西他赛,75mg/m,2,多柔比星,50mg/m,2,每,3,周,6,环磷酰胺,500mg/m,2,（,n=1630,）,Swain SM,Tang G,Geyer CE,et al.NSABP B-38:Definitive analysis of a randomized adjuvant trial comparing dose-dense(DD)ACpaclitaxel(P)plus gemcitabine(G)with DD ACP and with docetaxel,doxorubicin,and cyclophosphamide(TAC)in women with operable,node-positive breast cancer.J Clin Oncol 30,2012(suppl;abstr LBA1000).,主要终点：,DFS,；,次要终点：,OS,、毒性,TITLE,TITLE,NSABP B-38,：,TAC,方案的中性粒细胞减少性,发热等严重毒性和治疗相关性死亡发生率更高,NSABP B-38,发生率,(%),0.8%,0.3%,0.4%,P=0.2,发生率,(%),9%,4%,4%,8%,2%,2%,P0.001,P,紫杉醇剂量密集方案的,治疗指数,优于,TAC,方案,常规,3,周间隙,缩为,1,周,ECOG1199,：研究设计,Sparano JA,Wang M,Martino S,et al.Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer.N Engl J Med.2008;358(16):1663-71.,接受手术后的,腋窝淋巴结阳性或高危的腋窝淋巴结阴性的,乳腺癌患者,(n=4950),AC,方案,多柔比星：,60mg/m,2,环磷酰胺：,600mg/m,2,q3w 4,紫杉醇,175 mg/m,2,i.v 3h q3w 4,紫杉醇,80 mg/m,2,i.v 1h qw 12,多西他赛,100 mg/m,2,i.v 1h q3w 4,多西他赛,35 mg/m,2,i.v 1h;qw 12,R,主要终点：,DFS,ECOG1199,：紫杉醇单周方案的,DFS,获益更优,Sparano JA,Wang M,Martino S,et al.Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer.N Engl J Med.2008;358(16):1663-71.,无病生存率,(%),无病生存期,(,月,),多西他赛每周方案,多西他赛每,3,周方案,紫杉醇每周方案,紫杉醇每,3,周方案,5,年无病生存率,ECOG1199,：紫杉醇单周方案较,3,周方案,显著降低复发风险达,27%,Sparano JA,Wang M,Martino S,et al.Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer.N Engl J Med.2008;358(16):1663-71.,ECOG1199,：紫杉醇单周方案的,OS,获益更优,Sparano JA,Wang M,Martino S,et al.Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer.N Engl J Med.2008;358(16):1663-71.,总生存率,(%),总生存期,(,月,),5,年总生存率,多西他赛每周方案,多西他赛每,3,周方案,紫杉醇每周方案,紫杉醇每,3,周方案,ECOG1199,：紫杉醇单周方案较,3,周方案,显著降低死亡风险达,32%,Sparano JA,Wang M,Martino S,et al.Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer.N Engl J Med.2008;358(16):1663-71.,ECOG1199,：紫杉类,4,组方案中，,紫杉醇单周方案的严重毒性发生率最低,ECOG 1199,Sparano JA,Wang M,Martino S,et al.Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer.N Engl J Med.2008;358(16):1663-71.,紫杉醇单周方案,vs.,多西他赛,/,卡培他滨联合方案用于可手术乳腺癌患者的,III,期研究,Kelly CM,Green MC,Broglio K,et al.Phase III Trial Evaluating Weekly Paclitaxel Versus Docetaxel in Combination With Capecitabine in Operable,Breast Cancer.J Clin Oncol.2012;30:1-7.,可手术的,IIII,期乳腺癌患者,（,N=603,）,R,1:1,分层：辅助化疗,vs.,新辅助化疗,wP,紫杉醇,80mg/m,2,每周,12,周,（,n=302,）,XT,多西他赛,75 mg/m,2,D1,卡培他滨,1500 mg/m,2,D114,每,3,周,4,个周期,（,n=301,）,FEC,氟尿嘧啶,500 mg/m,2,表柔比星,100 mg/m,2,环磷酰胺,500 mg/m,2,每,3,周,4,个周期,主要终点：,RFS,；,次要终点：,OS,、,pCR,率、新辅助化疗后行,保乳手术的患者比例,与多西他赛每,3,周方案相比，,紫杉醇单周方案的,RFS,获益具有更优的趋势,无复发生存期,(,月,),无复发生存率,wPFEC,XT FEC,RFS,率：,90.7%(95%CI 86.4%93.7%),RFS,率：,87.5%(95%CI 82.7%91.1%),中位随访,50,个月,Kelly CM,Green MC,Broglio K,et al.Phase III Trial Evaluating Weekly Paclitaxel Versus Docetaxel in Combination With Capecitabine in Operable,Breast Cancer.J Clin Oncol.2012;30:1-7.,与多西他赛每,3,周方案相比，,紫杉醇单周方案的,OS,获益具有更优的趋势,总生存期,(,月,),总生存率,wPFEC,XT FEC,中位随访,50,个月,OS,率：,95.0%(95%CI 91.3%97.2%),OS,率：,92.2%(95%CI 88.0%95.0%),Kelly CM,Green MC,Broglio K,et al.Phase III Trial Evaluating Weekly Paclitaxel Versus Docetaxel in Combination With Capecitabine in Operable,Breast Cancer.J Clin Oncol.2012;30:1-7.,与多西他赛每,3,周方案相比，,紫杉醇单周方案的,2-3,级毒性发生率显著更低,2-3,级血液学毒性,发生率,(%),6.8,0.7,4.4,0,XT FEC,wPFEC,P0.001,P0.001,2-3,级非血液学毒性,发生率,(%),P0.001,P0.001,P0.001,P0.001,48.8,23.2,42.0,10.4,78.5,56.6,43.2,2.0,XT FEC,wPFEC,Kelly CM,Green MC,Broglio K,et al.Phase III Trial Evaluating Weekly Paclitaxel Versus Docetaxel in Combination With Capecitabine in Operable,Breast Cancer.J Clin Oncol.2012;30:1-7.,2012,版指南,vs.2013,版指南,乳腺癌的辅助化疗方案中，,乳腺癌,NCCN2013,版指南仍,1,类推荐剂量密集,AC,紫杉醇,(,单周或双周,),两种方案作为乳腺癌辅助化疗的优选方案；,TAC,方案从,2012,版,NCCN,指南推荐的优选方案降至,2013,版,NCCN,指南中的其他可选方案。,乳腺癌,NCCN2012,版指南,不含曲妥珠单抗的优选辅助化疗方案：,TAC(,多西他赛,/,多柔比星,/,环磷酰胺,),AC,紫杉醇剂量密集双周方案,AC,紫杉醇每周方案,TC(,多西他赛,/,环磷酰胺,),乳腺癌,NCCN2013,版指南,不含曲妥珠单抗的优选辅助化疗方案：,剂量密集,AC,紫杉醇剂量密集双周方案,剂量,密集,AC,紫杉醇每周方案,TC(,多西他赛,/,环磷酰胺,),其他化疗方案,：,TAC(,多西他赛,/,多柔比星,/,环磷酰胺,),NCCN Clinical Practice Guidelines in Oncology(NCCN Guidelines),.Breast Cancer.Version 3.2012.,NCCN Clinical Practice Guidelines in Oncology(NCCN Guidelines),.Breast Cancer.Version 1.2013.,比较两种含紫杉醇的辅助化疗方案,在乳腺癌患者中的应用,SWOG S0221,SWOG S0221,2013 ASCO,新进展,Budd GT,Barlow