乳腺癌前哨淋巴结活检-张永辉

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,乳腺癌腋窝前哨淋巴结活检临床进展,乳腺外科 张永辉,2018-3-25,乳腺癌腋窝前哨淋巴结活检,SLNB,概念及早期临床实践,SLNB,阴性免除腋窝清扫临床试验,SLNB,阳性选择性腋窝清扫临床试验,SLNB,可能改变临床实践的研究,SLNB,当前临床实践指南,乳腺癌腋窝前哨淋巴结活检,SLNB,的概念及回顾,前哨淋巴结的提出及应用,1977,年,Carcinoma of penis,Cabanas RM,开始使用名词：,sentinel lymph node,1992,年,Malignant melanoma,Alex JC,Krag DN,等将,SLNB,应用于恶性黑色素瘤治疗,1993,年,Breast cancer,Krag DN,首次将,SLNB,应用于乳腺癌治疗,Cabanas RM.Cancer.1977.,Alex JC,Krag DN,et al.Surg Oncol.1993.,Krag DN,et al.Surg Oncol.1993.,前哨淋巴结的概念,原发肿瘤经淋巴管引流至特定区域的第一站淋巴结,SLN is the node most likely to contain metastases.,If the sentinel node is negative,then the remainder of the nodal basin can be expected to be negative.,The sentinel node should therefore reflect the status of the entire axilla.,Wong J,et al.Ann Surg 1991.,乳腺癌,76-95%,淋巴引流首先至腋窝,乳腺癌总体的腋窝淋巴结转移发生率为,50%,早期乳腺癌人群（,T1-2 N0M0,），,70%,不伴淋巴结转移,腋窝淋巴结清扫作为乳癌根治术的必要组成部分，也产,了患肢水肿、相关疼痛、感觉障碍、关节活动下降等并,发症,SLNB,能否准确的反应腋窝淋巴结状态？是否能替代部分,ALND,避免不必要的术后并发症、且不增加复发、不影响生,存？,Suami H,et al.Ann Surg Oncol 2008.,乳腺癌腋窝淋巴结,意大利米兰试验：第一个乳腺癌前哨淋巴结活检随机对照试验,ALND,组：前哨阳性,83,例，阴性,174,例，阴性者后续,ALND8,例淋巴结阳性。,specificity,100%,（阳性者后续,ALND,状态未提）,false-negative rate,8.8%,8/,（,83+8,）,(95%CI,3.9 to 16.6),negative predictive value,95.4%,（,174-8,）,/174,(95%CI,91.1 to 98.0),sensitivity rate,91.2%,83/,（,83+8,）,入组,516,名原发肿瘤,2cm,保乳术患者,对照组,257,例：,SLNB+ALND,试验组,259,例：,SLNB,，仅阳性者,ALND,Veronesi U,et al.N Engl J Med.2003.,意大利米兰试验：并发症,随访,24,月，,SLNB,组具有,更少的疼痛、麻木、水肿，,更好的上肢活动度,Veronesi U,et al.N Engl J Med.2003.,意大利米兰试验：不良事件与生存,Veronesi U,et al.N Engl J Med.2003.,中位随访,46,月，,SLNB,组与,ALND,组均未发生查体及超声所见的转移；,两组患者总生存无统计学差异。,2005 Lyman GH et al.J Clin Oncol,2005,ASCO,乳腺癌治疗指南开始推荐,2006 NCCN Clinical Practice Guidelines in Oncology,NCCN,临床实践指南推荐,乳腺癌腋窝前哨淋巴结活检进入临床指南,Lyman GH,et al.J Clin Oncol.2005.,乳腺癌腋窝前哨淋巴结活检,SLNB,阴性免除腋窝清扫,SLNB,阴性免除腋窝清扫,NSABP B-32,randomised phase 3 trial,1999-5-12004-2-29,共,5611,名女性乳腺癌患者,入组,Krag DN,et al.Lancet Oncol.2007.,NSABP B-32,randomised phase 3 trial,Krag DN,et al.Lancet Oncol.2007.,患者特征,FNR,分析,false-negative rate,9.8%,SLN(-),nonSLN,（,+,）,3.9%,SLN(+),nonSLN(+),38.6%,NSABP B-32,randomised phase 3 trial,ALND SLNB,腋窝复发,8,（,0.4%,）,vs,14,（,0.7%,）,OS 91.8%vs 90.3%,8,年随访结果,Krag DN,et al.Lancet Oncol.2010.,SLNB,阴性免除腋窝清扫,NSABP B-32,randomised phase 3 trial,10,年随访结果,ASCO 2013,Node negative patient outcomes,SLN+ALND,N=1975,SLN only,N=2011,Overall survival,85.4%,87.5%,Disease-free survival,77.0%,81.5%,Local-regional recurrence,84,（,4.3%,）,81,（,4.0%,）,SLN,组,VS SLN+ALND,组，,10,年,OS,、,DFS,及区域控制无,统计学差异,SLNB,阴性免除腋窝清扫,ASCO 2013,结论：,SLNB(-),组与,SLNB,（,-,）继行,ALND,组 随访,8,年、,10,年的,OS,、,DFS,无统计学差异。,对于临床检查和,SLN,阴性的患者，避免,ALND,是安全、合理的。,NSABP B-32,randomised phase 3 trial,B-32,与米兰试验,10,年随访结果一致，,SLN,阴性免除腋窝清扫是安全的,Veronesi U,et al.Ann Surg.2010.,SLNB,阴性免除腋窝清扫,乳腺癌腋窝前哨淋巴结活检,SLNB,阳性选择性腋窝清扫临床试验,1-2,个前哨淋巴结阳性,腋窝清扫,vs,非腋窝清扫？,c T1-2,N0,M0 breast cancer,1-2 positive SNs by H&E staining,Lumpectomy,R,ALND,No further axillary,treatment,Breast RT,systemic,adjuvant,treatment,or,both,Follow up,ACSOG Z0011 trail,III noninferiority Randomized trial,Giuliano AE,et al.JAMA.2011.,ACSOG Z0011 trail,患者基线情况及肿瘤特征,Giuliano AE,et al.JAMA.2011.,从,1999,年,5,月至,2004,年,12,月,ALND,组,445,例，,SLND,组,446,例,末次随访时间,2010,年,3,月,4,日,比较两组的,DFS OS,ACSOG Z0011 trail,Giuliano AE,et al.JAMA.2011.,ACSOG Z0011 trail,腋清,VS,非腋清，,5,年,OS,及,DFS,无统计学差异,Giuliano AE,et al.JAMA.2011.,ACSOG Z0011 trail,腋清,VS,非腋清，,10,年,OS,及,DFS,无统计学差异,SLND alone 86.3%(95%CI,82.2%89.5%),ALND 83.6%(95%CI,79.1%87.1%),SLND alone 80.2%(95%CI,75.6%84.1%),ALND 78.2%(95%CI,73.5%82.2%),Giuliano AE,et al.JAMA.2017,ACSOG Z0011 trail,OS,根据,HR,分层分析：,ALND vs SLND,差异无统计学意义,Giuliano AE,et al.JAMA.2017,ACSOG Z0011 trail,结论,接受保乳术,+,全乳放疗的,SLN1-2,枚阳性患者（非前哨淋巴结转移,30%,）,，在接受系统辅助治疗情况下，单独,SLNB,的生存率不劣于,ALND,组,Giuliano AE,et al.JAMA.2017,Giuliano AE,et al.JAMA.2011.,大部分为,1-2,枚小于,2mm,微小转移,无结外浸润,c T1-2,N0,M0 breast cancer,BCS,+Mastectomy,R,ALND,n=464,Follow up,n=467,one or more micrometastatic,（,MIC+ITC),n=931,IBCSG 23-01,trail,III,multicenter noninferiority,Randomized trial,SLNB,Galimberti V,et al.Lancet Oncol.2013.,IBCSG 23-01 trail,Galimberti V,et al.Lancet Oncol.2013.,患者特征及辅助治疗,IBCSG 23-01 trail,Galimberti V,et al.Lancet Oncol.2013.,患者特征及辅助治疗,IBCSG 23-01 trail,Galimberti V,et al.Lancet Oncol.2013.,腋清,VS,非腋清，,OS,及,DFS,无统计学差异,IBCSG 23-01 trail,Galimberti V,et al.Lancet Oncol.2013.,在,1-2,枚前哨淋巴结微转移（非前哨转移,13%,）的早期乳腺癌患者中，两,组,5,年,DFS,及,OS,相当，免除腋窝淋巴结清扫没有产生不利影响。,与,Z0011,不同，其包含,9%,乳房切除患者，亚组分析显示这部分患者去除,ALND,似乎可行，但样本量小似乎不够充分。,结 论,乳腺癌腋窝前哨淋巴结活检,SLNB,可能改变临床实践的研究,乳腺癌腋窝前哨淋巴结活检,问题,1,：,cN,+,新辅助化疗后的前哨淋巴结活检,ACOSOG Z1071,FNR,高是新辅助化疗后,SLNB,是否可行的关键问题,目的：,确定术前穿刺确诊淋巴结阳性乳腺癌新辅助化疗后前哨淋巴结活检（,SLNB,）,的假阴性率（,FNR),。,前瞻性、多中心、,，,N=756 T0-4N1-2M0,患者，穿刺病理证实,cN1/2,后,NAT,Boughey JC,et al.JAMA.2013,乳腺癌腋窝前哨淋巴结活检,问题,1,：,cN,+,新辅助化疗后的前哨淋巴结活检,ACOSOG Z1071,结果：,Boughey JC,et al.JAMA.2013,腋窝总体,pCR 41%,（,未按分子分型统计,）,663,个,cN1,病例中，,SLN,检出率,92.9%,，,38,个,cN2,病例中检出率,89.5%,cN1,中当,SLN,检出,2,枚时，,FNR 12.6%,；,cN2 FNR 0%,3,枚时，,FNR 9.1%,203,例,NAT,前转移淋巴结放置标记夹，并在,SLNB,时清除标记淋巴结，,FN