三阴性乳腺癌的治疗现状

Click to edit Master text styles,Second level,Third level,Fourth Level,Fifth Level,Click to edit Master title style,#,三阴性乳腺癌的治疗现状,三阴性乳腺癌的治疗现状,第1页,年,St Gallen,共识乳腺癌亚型,亚型 定义,Luminal A,型,ER,和（或）,PR,阳性，,HER2,阴性，,Ki67,低表示（,14%,）,Luminal B,型,Luminal B,（,HER2,阴性），,ER,和（或）,PR,阳性，,HER2,阴性，,Ki67,高表示（,14%,）,Luminal B,（,HER2,阳性），,ER,和（或）,PR,阳性，,HER2,过表示或增殖，,Ki67,任何水平,HER-2,过表示型,HER2,阳性（非,Luminal,），,ER,和,PR,缺失，,HER2,过表示或增殖,基底样型,三阴性（导管），,ER,和,PR,缺失，,HER2,阴性,三阴性乳腺癌的治疗现状,第2页,一、三阴性乳腺癌（,TNBC,）,:,概念,Triple negative andbasal-like,Basal,but not triple negative,15-40%are ER+,PR+or HER2+,Triple negative,but not basal,Clinical assay(IHC),Gene,arrays,ER-/PgR-/HER2-,三阴性乳腺癌的治疗现状,第3页,BRCA1,、,Basal-Like,、,TNBC,乳腺癌关系,Leslie K.et al.Adv.Anat.Pathol.;14:419-430,Basal-like,Triple Negative,BRCA1,三阴性乳腺癌的治疗现状,第4页,二、,TNBC,风险原因,(,排除,BRCA,状态,),Younger age at menarche,Higher parity,Younger age at full term pregnancy,Shorter duration of breast feeding,High body mass index(BMI),High waist to hip ratio,Lack of exercise,Fulford et al,Histopathology;Livasy et al,Mod Pathol,Bauer KR Cancer Carey JAMA,三阴性乳腺癌的治疗现状,第5页,三、,TNBC,预后原因,Large tumor size,Presence of nodal metastasis,Presence of distant metastasis,Presence of central necrosis,Absence of androgen receptor,Basal phenotype,EGFR,Age 40?(Liedtke et al.ASCO),三阴性乳腺癌的治疗现状,第6页,占全部乳腺癌病理类型,10.0%20.8%,；,含有特殊生物学行为和临床病理特征；,预后较其它类型差；,多发生于绝经前年轻女性；,尤其是非洲裔美国妇女：,50,岁以下非洲裔美国妇女发病率甚达,39%,；,白种人则仅为,16%,。,四、,TNBC,流行病学,三阴性乳腺癌的治疗现状,第7页,组织学分级多为,级,细胞增殖百分比较高,c-kit,、,p53,、,EGFR,表示多为阳性,基底细胞标志物细胞角蛋白,(CK)5/6,、,17,也多为阳性。,五、,TNBC,分子病理特征,三阴性乳腺癌的治疗现状,第8页,临床表现为侵袭性病程,；,远处转移风险较高,内脏转移几率较骨转移高,脑转移几率也较高。,预后较差,死亡风险较高。,六、,TNBC,临床特征,三阴性乳腺癌的治疗现状,第9页,TNBC:Shorter Median Time fromDistant Relapse to Death,22 months,9 months,Dent R,Trudeau M,Pritchard K,Hana W,Narod S.et al.,Clinical Cancer Res,“Triple Negative”,Other Breast Cancer,三阴性乳腺癌的治疗现状,第10页,TNBC,与,Non-TNBC,生存比较,三阴性乳腺癌的治疗现状,第11页,TNBC:Recurrence and Survival,Increased likelihood of distant recurrence,Visceral metastases to brain,lung,and distant nodal sites common,Metastases to bone and liver less common,Relapse most likely during the first 3 y after therapy,Majority of deaths within first 5 y,By 10 years,OS differences between TNBC&non-TNBC are minimal,Kim et al.SABCS.Abstract 4065,.,三阴性乳腺癌的治疗现状,第12页,七、,TNBC,治疗策略,TNBC paradox:chemosensitive,but relapse more aggressive with worse OS,Cannot treat with standard targeted therapies(hormonal therapy or anti-HER2 agents),Question of bevacizumab open,Limited data available from prospective trials in this population,Best available data mostly retrospective subpopulation analyses,No specific recommendations within recognized treatment guidelines,Manage same as other BCs with same grade&stage,Anthracycline,Taxanes,Ixabepilone,Platinum agents,Biologic agents,三阴性乳腺癌的治疗现状,第13页,(1),三阴性乳腺癌对标准化疗疗效,三阴性乳腺癌的治疗现状,第14页,(2),转移性,TNBC,较快发生化疗耐药,三阴性乳腺癌的治疗现状,第15页,（,3,）,TNBC,对新辅助化疗有较高,pCR,率,Compared with ER+luminal disease,TNBC and HER2+/ER-BC pts had:,Decreased DFS(p=0.04),Decreased OS(p=0.02),三阴性乳腺癌的治疗现状,第16页,早期,TNBC,化疗,CR,者预后好,三阴性乳腺癌的治疗现状,第17页,TNBC,对,新辅助化疗有较高,pCR,率,1118 pts received T-FAC,Note Paradox:,Despite increase in pCR rate,TNBC had worse outcome(OS),TNBC,Non-TNBC,P Value,Pts,no(%),265(23),863(77),pCR,%,22,11,0.034,PFS(3-y),%,63,76,0.0001,OS(3-y),%,74,89,0.0001,Liedtke et al.J Clin Oncol.;26:1275-1281.,三阴性乳腺癌的治疗现状,第18页,(4),Adjuvant,Anthracycline+Taxane for TNBC,Hugh et al.J Clin Oncol.;27:1168-1176.,DFS(BCIRG 001):TAC vs FAC(n=192),OS:AC,T vs ATT(N=378),Loesch et al.J Clin Oncol.;28:2958-2965,三阴性乳腺癌的治疗现状,第19页,(5)sequential chemotherapy,for TNBC,PACS 01,试验（,期随机临床试验）,针对淋巴结阳性乳腺癌患者,FEC,6,VS,FEC,3,序贯,D,3,，,序贯治疗组中,基底样乳腺癌患者,无病生存,(DFS),率,(P=0.05),和总生存,(OS),率,(P=0.005),很好。,所以,即使基底样乳腺癌预后较差,但对,FEC,序贯多西他赛化疗有很好反应。,三阴性乳腺癌的治疗现状,第20页,高危乳腺癌术后辅助化疗,期临床试验,(,年,ASCO,汇报,),A,组：,AC,4,序贯,P,(175 mg/m2,Q3W),4,B,组：,AP,4,序贯,P,(80 mg/m2,QW),12,结论,:,对于三阴性乳腺癌,AP,序贯,P,组五年,OS,优势愈加显著,(87%,对,79%,P=0.037),。,紫杉类药品对,TNBC,有一定疗效,序贯方式也可能是其取得很好疗效方式之一。,研究结果均来自试验亚组分析或回顾性分析,尚需前瞻性研究证实。,三阴性乳腺癌的治疗现状,第21页,(6),Platinum Agents for TNBC,Trial,Phase/No.of TNBC pts,Setting,Regimen,Outcome in TNBC,II(n=12),Neoadjuvant,Carbo-P vs carbo-P-H,pCR=67%,II(n=30),Neoadjuvant TNBC,E-Cis-F,P,pCR=40%;ORR=86%,Silver(),II(n=28),Neoadjuvant TNBC,Cis,pCR=22%,Leone(),Retro(n=125),Sikov(),Platinum+D,pCR=34%,OS 5yr=55%,OS greater with cis vs carbo,Kern(),II(n=10),Torrisi(),Carbo+D,pCR=40%,Uhm(),II(n=36),Metastatic,Carbo-P or Cis-P,ORR 37.5%,Wang(),II(n=65),Metastatic,Gem-carbo,PFS=6.2 months,ORR=62.2%,Carbo=carboplatin;Cis=cisplatin;D=docetaxel;E=epirubicin;F=5-FU;H=trastuzumab;P=paclitaxel;retro=retrospective.,三阴性乳腺癌的治疗现状,第22页,(7),High dose chemotherapy(HDC)for TNBC,WSG AM 01,试验,9,个以上淋巴结阳性乳腺癌患者分为两组,A,组：密集,EC,2,序贯,HDC,2(EPI 90 mg/m2,CTX 3 g/m2,塞替派,400 mg/m2),B,组：密集,EC,4,序贯 密集,CMF,3,结果表明,年轻三阴性乳腺癌患者从,HDC,中获益最多。,三阴性乳腺癌的治疗现状,第23页,(8)Molecular targeted therapies for TNBC,Cell Cycle,Transcriptional Control,MAP Kinase Pathway,Akt Pathway,EGFR tyrosine kinase,c-KIT tyrosine kinase,DNA Repair pathway-platinum agents,PARP inhibitors,Angiogene