早期乳腺癌内分泌治疗的一些进展 南京医科大学第一附属医院乳腺内分泌外科 王水

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Early Breast Cancer:Endocrine Therapy,早期乳腺癌内分泌治疗的一些进展,南京医科大学第一附属医院乳腺内分泌外科,王 水,乳腺癌：一种全身性疾病,治疗：综合性,规范化：循证医学,个体化：,target,&tailor,2007,年,St,Gallen,共识,HER2/neu,基因过表达,HER2,低表达,HER2,过表达,内分泌应答,高应答,应答不完全,无应答,高应答,应答不完全,无应答,绝经状况,前,后,前,后,前和后,前,后,前,后,前和后,低危,淋巴结阴性且具有以下所有特征：,pT,2cm,Grade 1,，无血管侵袭，,HER2(-),，,ER,和,/,或,PR,表达，年龄,35,岁,E,E,E,E,中危,淋巴结阴性且至少具有以下一个特征：,pT,2cm,Grade 2-3,，血管侵袭，,HER2(-),，,ER,和,/,或,PR,阴性，年龄,4,个淋巴结阳性,C,E,C,E,C,E,C,E,C,C,E,+,Tr,C,E,+,Tr,C,E,+,Tr,C,E,+,Tr,C,+,Tr,乳腺癌内分泌治疗的,三,个重要标志,双卵巢切除去势术,他莫昔芬标准地位的确立,第三代芳香化酶抑制剂,挑战,他莫昔芬标准地位,他莫昔芬治疗乳腺癌的标准地位,EBCTCG.Lancet 2005,复发率,(%),复发,时间（年）,乳腺癌死亡率,60,15,年受益率,11.8%(SE 1.3),时序检验,2p0.00001,乳腺癌死亡率,(%),50,40,30,20,10,0,服用他莫昔芬约,5,年,25.6%,安慰剂,34.8%,0,5,10,15,时间（年）,11.9,25.7,8.3,17.8,60,50,40,30,20,10,0,15,年获益,11.8%(SE 1.3),时序检验,2p5mm),的患者，改用依西美坦治疗后，其中,50,的子宫内膜转变为正常,可显著延长骨折的出现,Coombes,et al.,J,Clin,Oncol,.,2006;24(18S):933s.Abstract LBA527,The,Intergroup,Exemestane,Study(IES)group.Lancet.2007 Feb 17;369(9561):559-70.,AIs,Extended,目前结论,MA17,、,B-33,、,ABCSG 6a,等研究：,Extended,方案能显著降低患者复发风险,Extended,方案显示良好的安全性,2007,年,St,Gallen,共识,绝经后患者芳香化酶抑制剂的应用策略,委员会倾向于,Switch,方案，即他莫昔芬治疗,2-3,年后换用,AIs,，少数人同时支持起始就使用,AIs,，几乎没有人倾向于他莫昔芬治疗,5,年后换用,AIs,的策略,对于已经完成,5,年他莫昔芬治疗的病人，大部分委员支持在淋巴结阳性的病人中再用一段时间的,AIs,对于高危病人或,HER2,阳性的病人，更多接受起始使用,AIs,有过半的委员也支持对于接受,SSRI,类抗抑郁药的病人起始使用,AIs,AI,的安全性特征与,TAM,不同,他莫昔芬：,血栓栓塞,子宫内膜问题、阴道出血,/,排液等妇科事件,芳香化酶抑制剂：,肌肉关节症状,BMD,降低，骨质疏松,AI,对心血管系统和血脂代谢的影响,目前仍然存在的问题,临床上如何判断真绝经？,Upfront,、,Switch,或,Extended,方案的合理选择？,内分泌药物的合理选择？,内分泌药物的安全性问题？如何介入？,如何确定内分泌治疗的有效性？,延长治疗时间、增加治疗剂量、辅助其它药物能否提高疗效和安全性？,ATLAS:Is There Benefit to Longer,Tamoxifen,(5+Years)Therapy?,5 years of,tamoxifen,therapy in patients with ER-positive breast cancer,Reduces annual recurrence rate through first decade,Risk of recurrence persists,leading to questions of possible benefit to longer therapy,Previous NSABP B-14 randomized extension trial showed,no additional benefit,beyond 5 years,1,Study may have been underpowered,Current ATLAS trial,2,Larger study of patients randomized to 5 or 10 years of,tamoxifen,1.Fisher B,et al.J,Natl,Cancer Inst.2001;93:684-690.,2.,Peto,R,et al.SABCS 2007.Abstract 48.,ATLAS:Longer,vs,Shorter,Tamoxifen,in ER-Positive Breast Cancer,Tamoxifen,treatment for,5 additional years,Patients with breast cancer treated,with adjuvant,tamoxifen,for 5 years,(N=11,500),No additional,Tamoxifen,Year 10,Year 5,Peto,R,et al.SABCS 2007.Abstract 48.,Annual assessments included compliance,hospital admissions,breast cancer recurrence(or new,contralateral,disease),other new primary cancer,and death.,ATLAS:Disease Recurrence and OS Rates,RR significantly lower with continued,tamoxifen,;trend toward OS benefit(NS),Caveats,Number of patients with ER-positive cancer probably 90%(not 100%),Some patients with untested tumors likely ER negative,Tamoxifen,benefit probably underestimated since compliance rate 80%,Peto,R,et al.SABCS 2007.Abstract 48.,Parameter,Annual Event Rate,%of Patients,Ratio of Rates With Continued,vs,Stopped,Tamoxifen,(SE),Continued TAM,Stopped TAM,All recurrences/yr,2.9,3.4,0.866(0.048*),Years 0-1,3.2,3.6,0.89(0.07),Years 2-4,2.8,3.3,0.87(0.08),Years 5+,2.4,3.0,0.77(0.12),Deaths,1.4,1.5,0.895(0.070),Years 0-1,1.0,1.0,1.00(0.14),Years 2-4,1.6,1.8,0.90(0.10),Years 5+,1.9,2.4,0.79(0.13),P,=.005,ATAC:A,vs,T in Postmenopausal Women With Localized Breast Cancer,1.Howell A,et al.Lancet.2005;365:60-62.,2.Forbes JF M,et al.SABCS 2007.Abstract 41.,Postmenopausal women with early-stage invasive breast cancer,(N=6241),Anastrozole,(n=3125),Tamoxifen,(n=3116),Long-term,follow-up,Year 5,Previous ATAC results showed less disease recurrence in postmenopausal women with localized disease on,anastrozole,vs,tamoxifen,1,Anastrozole,well tolerated but higher risk of fractures,Current study assessed long-term efficacy and toxicity of anastrozole,2,ATAC:Efficacy Results,Outcome(Hormone Receptor,Positive P,atients),HR(95%CI),P,Value,DFS,0.85(0.76-0.94),.003,TTR,0.76(0.67-0.87),.0001,TTDR,0.84(0.72-0.97),.022,CLBC,0.60(0.42-0.85),.004,OS,0.97(0.86-1.11),.70,Death after recurrence,0.90(0.75-1.07),.20,Forbes JF,et al.SABCS 2007.Abstract 41.,Long-term results showed that,anastrozole,superior to,tamoxifen,for DFS,TTR,TTDR,and CLBC,but not for OS and deaths after recurrence,Similar findings observed when analyses restricted to hormone receptor,positive population,ATAC:Adverse Events for,Anastrozole,vs,Tamoxifen,Forbes JF,et al.SABCS 2007.Abstract 41.,Serious Adverse Events,n(%),On Treatment,Off Treatment,Anastrozole,(n=3092),Tamoxifen,(n=3094),Anastrozole,(n=3092),Tamoxifen,(n=3094),Fracture episodes*,375(12.13),234(7.56),146(4.72),143(4.62),Treatment-related events,153(4.95),284(9.18),49(1.58),57(1.84),Myocardial infarction,34(1.10),33(1.07),26(0.84),28(0.90),Cerebrovascular,accident,20(0.65),34(1.10),22(0.71),20(0.65),Endometrial cancer,4(0.13),12(0.39),1(0.03),12(0.34),Excess in fractures diminished after cessation of therapy,RR of frac