,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,2018/12/2,#,内 容,乳癌个体化治疗研究,临床实践,-,方案选择,内 容乳癌个体化治疗研究,1,乳腺癌,系统,辅助治疗取得的进展,疾病相关复发风险降低百分比,0,10,20,30,40,17%,42%,46%,31%,CEF vs CMF,Levine 2005,AC,T vs AC,Henderson 2003,Piccart 2005,三苯氧胺,vs,安慰剂,Fisher 2004,DAC vs FAC,Martin 2005,28%,HER2+,&,HER2-,Romond 2005,50,52%,HER2+,化疗,+,赫赛汀,vs,化疗,化疗,赫赛汀,vs,化疗,乳腺癌系统辅助治疗取得的进展疾病相关复发风险降低百分比010,2,辅助治疗方案选择应有循证医学依据,整体治疗计划,方案组成,剂量,疗程,选择与临床试验的入组条件最相近的方案,NCCN,指南（英文版、中文版）,St Gallen,专家共识,辅助治疗方案选择应有循证医学依据 整体治疗计划NCCN指,3,早期乳癌术后辅助化疗课件,4,INT,C9741,剂量密度 与 标准剂量,中位随访,5,年,INT C9741 剂量密度 与 标准剂量中位随访5年,5,C9741DFS,：,ER,状态与剂量密集,随访,69,个月,Disease-Free Survival,0.0,0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8,0.9,1.0,0,1,2,3,4,5,6,7,Year,ER+q3wk,ER-q3wk,ER-q2wk,ER+q2wk,ER+q2 n=636 Events=126,ER-q2 n=336 Events=99,ER+q3 n=639 Events=133,ER-q3 n=327 Events=127,P,=.014,P,=NS,ER=estrogen receptorsWith permission from Hudis C,et al.2005 San Antonio Breast Cancer Symposium.Abstract 41.,C9741DFS：ER 状态与剂量密集Disease-,6,分子分型与病理免疫组化分型的大致关系,Luminal A,ER+Her-2 -,、分化好、,Ki-67,低,Luminal B,ER+Her-2 -,、分化差、,Ki-67,高,Her-2 positive,Her-2+HR+,Her-2+HR-,Basal-like,Her-2,ER,PR,(80%),Her-2+ER,Normal-like,Her-2-,分子分型与病理免疫组化分型的大致关系 Luminal AE,7,WWW.Pnas.org/cgi/doi/10.1073/pnas.191367098,基因分型预后,WWW.Pnas.org/cgi/doi/10.1073,8,PAM 50,预测不同亚型生存率,Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes,Joel S.Parker,Michael Mullins,Maggie J Clin Oncol 27:1160-1167,PAM 50 预测不同亚型生存率Supervised Ris,9,个体化治疗时代,乳腺癌不是一种单一的疾病，,而是一组生物学行为不同的疾病。,术后辅助化疗不再有“通用”的方案,个体化治疗时代,10,RANDOMIZE,tamoxifen x 5 yrs,Albain,et al.Breast Cancer Res Treat 2005,n=1477,CAF x 6,then,tamoxifen,CAF x 6,with concurrent tam,(n=361),(n=550),(n=566),SWOG 8814,Postmenopausal N+ER+,RANDOMIZEtamoxifen x 5 yrs,11,SWOG 8814/TBCI 0100 Sample Size for This Analysis,Patients with samples-666,(,45%of parent trial),RT-PCR obtained-601(90%),Tamoxifen alone 148,CAFT(concurrent)234,CAF-T(sequential)219,Final sample for primary analysis,148+219=367,(40%of parent trial),SWOG 8814/TBCI 0100 Sample S,12,0.00,0.25,0.50,0.75,1.00,Disease-free survival,0,2,4,6,8,10,Years since registration,Tamoxifen(n=55,15 events),CAF-T (n=91,26 events),Stratified log-rank p=0.97 at 10 years,Low risk(RS 18),Disease-Free Survival by Treatment,低,RS,者化疗无受益,0.00,0.25,0.50,0.75,1.00,Disease-free survival,0,2,4,6,8,10,Years since registration,Tamoxifen (n=47,26 events),CAF-T (n=71,28 events),Stratified log-rank p=0.033 at 10 years,High risk(RS,31),Disease-Free Survival by Treatment,0.00,0.25,0.50,0.75,1.00,Disease-free survival,0,2,4,6,8,10,Years since registration,Tamoxifen (n=46,22 events),CAF-T (n=57,20 events),Stratified log-rank p=0.48 at 10 years,Intermediate risk(RS 18-30),Disease-Free Survival by Treatment,高,RS,者化疗明显受益,RS,与化疗获益的关系,0.000.250.500.751.00Disease-fr,0.00,0.25,0.50,0.75,1.00,Disease-free survival,0,2,4,6,8,10,Years since registration,Tamoxifen(n=57,20 events),CAF-T (n=85,30 events),Stratified log-rank p=0.81 at 10 years,HER2 Negative,and,ER Allred 7-8,0.00,0.25,0.50,0.75,1.00,Disease-free survival,0,2,4,6,8,10,Years since registration,Tamoxifen(n=73,36 events),CAF-T (n=112,39 events),Stratified log-rank p=0.011 at 10 years,HER2 Positive,or,ER Allred 3,。,2009,年的共识加入了,Ki 67,2007年St Gallen早期乳腺癌初始治疗国际专家共识低,18,早期乳癌术后辅助化疗课件,19,三阴性（,ER,、,PgR,、均为阴性,HER2,）,HER2,阳性,ER,阳性而,HER2,阴性,内分泌治疗？抗,Her-2,治疗？化疗？,三阴性（ER、PgR、均为阴性HER2）HER2阳性ER阳性,20,内分泌治疗,适应症：所有激素受,+,PR+ER,：意义未明，建议重新检测免疫,组化,ER,PR,：病理类型较好的，如管样癌、,胶样癌，重新检测免疫组化,药物选择：,内分泌治疗适应症：所有激素受+,21,哪些患者无需化疗，哪些患者需化疗？,T,1 cm,、,N0,、无其他潜在复发风险（脉管浸润）者，可不给予任何全身治疗，激素受体反应型者可接受内分泌治疗。,三阴性患者由于高复发风险，绝大部分应接受化疗，而对于特殊类型乳腺癌如髓样癌（如诊断此型应与病理科再次确认，因典型髓样癌极少见）、顶泌型癌及腺囊癌，由于其低危性可不接受化疗，但若为三阴性患者也应接受化疗。,哪些患者无需化疗，哪些患者需化疗？T1 cm、N0、无其他,22,在选择化疗适应证时对传统的预后因子还应予以充分的考虑，这些因子包括：淋巴结转移、,Ki 67,（低表达,15%,，中表达,15%,30%,，高表达,39%,）、有丝分裂相高，年龄、脉管浸润、,Her-2+,、激素受体等，当传统的预后因子对指导化疗无助时，多基因测定结果可作为参考因素之一。,哪些患者无需化疗，哪些患者需化疗？,在选择化疗适应证时对传统的预后因子还应予以充分的考虑，这些因,23,HR,阳性、,Her-2,阴性患者化疗方案选择,临床病理,特征,内分泌治疗,+,化疗的相对指征,不能决定,单用内分泌,治疗指征,ER,与,PR,低表达,高表达,组织学分级,G3,G2,G1,增殖,高,中,低,淋巴结,阳性（,4,个）,阳性（,1-3,个）,阴性,脉管浸润,有广泛浸润,无广泛浸润,肿瘤大小,5cm,2.1-5cm,2cm,患者意愿,任何可用方案,避免化疗相关副作用,多基因检测,评分高,评分中,评分低,HR阳性、Her-2阴性患者化疗方案选择临床病理内分泌治疗,24,指南推荐方案,优先采用方案,TAC,、,AC,、,剂量密集,AC,序贯紫杉醇、,AC,序贯每周紫杉醇、,TC,，,其他可选方案,FEC,、,CAF,、,EC,、,单周密集序贯,A-T-C,、,CMF,、,EFC,序贯单周紫杉醇,指南推荐方案优先采用方案TAC、其他可选方案FEC、,25,a,Based on small subgroups of patients with HER2-positive breast cancer;,b,DDFS;CTx,chemotherapy;AC,doxorubicin,cyclophosphamide;P,paclitaxel;T,docetaxel;Carbo,carboplatin;V,vinorelbine;CEF,cyclophosphamide,epirubicin,5-fluorouracil,Her-2,阳性者抗,Her-2,治疗,-,赫,赛汀治疗持续无病生存获益的研究,3,4,5,4,Gianni et al 2008;Gianni et al 2009;Joensuu et al 2009;Slamon et al 2006;Perez et al 2007;Smith et al 2007;Spielmann et al 2007,3,3,中位随访时间,年,DFS,获益,B-31/N9831,AC,PH,HERA,化疗,赫赛汀,1,年,FinHer,a,VH/TH,CEF,b,PACS-04,a,CTx,H 1 year,BCIRG 006,AC,TH,TCarboH,n=231,n=528,NOAH,CTx/H,H 1 year,3,0,1,2,倾向赫赛汀治疗,倾向非赫赛汀治疗,HR,aBased on small subgroups of p,26,1-,年赫赛汀治疗持续降低,33,的死亡机会,0,1,2,B-31/N9831,AC,P,H,3,HERA,CTx,H 1 year,4,OS,获益,BCIRG 006,AC,T,H,3,TCarboH,3,倾向赫赛汀治疗,倾向非赫赛汀治疗,HR,5,FinHer,VH/TH,C