现代乳癌内分泌治疗新方法.pptx

乳癌内分泌治疗乳癌内分泌治疗新思绪和临床实践新思绪和临床实践现代乳癌内分泌治疗新方法第1页乳癌治疗伎俩乳癌治疗伎俩Surgery 手术Radiation therapy 放疗Chemotherapy 化疗Hormone therapy 内分泌治疗Biotherapy 生物治疗New therapies 新治疗现代乳癌内分泌治疗新方法第2页乳癌内分泌治疗发展乳癌内分泌治疗发展197019801990TamoxifenTamoxifenMAAG新芳香化酶抑制剂新芳香化酶抑制剂新芳香化酶抑制剂新芳香化酶抑制剂Exemestane/MA新芳香化酶抑制剂新芳香化酶抑制剂新芳香化酶抑制剂新芳香化酶抑制剂Tamoxifenpure A.E.?MAI IIIIII IIIIIIIIIIII IIIIIIIIIII现代乳癌内分泌治疗新方法第3页Hormone Therapy Response Rate(%)in Different Receptor Status现代乳癌内分泌治疗新方法第4页Survival by Response Arimidex 1 mg0 020204040606080801001000 01 12 23 34 4CR or PRCR or PRStable Stable 24 24 wkswksProgressionProgressionYears from RandomisationYears from Randomisation%Survival 现代乳癌内分泌治疗新方法第5页MAAG Prevention DCIS/Neoadj 5 yearsMetastaticDisease 1st2nd3rdAdjuvant TAM TAMTAMTAMOVABL三苯氧胺三苯氧胺（TAM)最主要乳癌内分泌治疗药品最主要乳癌内分泌治疗药品现代乳癌内分泌治疗新方法第6页Tamoxifen for 5 Years vs No TreatmentPercentYearsER+85.285.276.176.168.268.273.773.762.762.754.954.911.5(11.5(SE 0.9)SE 0.9)13.4(13.4(SE 1.1)SE 1.1)13.4(13.4(SE 1.4)SE 1.4)68.2%54.9%020406080100051015vsRecurrencesBreast Deaths020406080100051015ER+73.0%64.0%91.491.480.980.973.073.087.887.873.273.264.064.03.6(3.6(SE 0.7)SE 0.7)7.8(7.8(SE 1.0)SE 1.0)9.0(9.0(SE 1.4)SE 1.4)vsYearsPercent现代乳癌内分泌治疗新方法第7页Tamoxifen Adjuvant Therapy for EBC辅助内分泌治疗辅助内分泌治疗决定原因决定原因是激素受体情况是激素受体情况ERER阳性阳性效果最好效果最好 8现代乳癌内分泌治疗新方法第8页Tamoxifen Adjuvant Therapy for EBC适当适当TAMTAM服药时间服药时间为为5 5年年9现代乳癌内分泌治疗新方法第9页Tamoxifen Adjuvant Therapy for EBC ERER阳性阳性不论年纪大小都可用不论年纪大小都可用TAMTAM10现代乳癌内分泌治疗新方法第10页Tamoxifen Adjuvant Therapy for EBC降低对侧乳癌发生降低对侧乳癌发生增加子宫内膜癌风险增加子宫内膜癌风险11现代乳癌内分泌治疗新方法第11页Tamoxifen Adjuvant Therapy for EBC ERER阳性阳性TAMTAM和化疗适用和化疗适用比单用比单用TAMTAM更有效更有效CAFCAF与与TAMTAM 序贯适用序贯适用比比同时效果同时效果更加好更加好 现代乳癌内分泌治疗新方法第12页MAAG Prevention DCIS/Neoadj 5 yearsMetastaticDisease 1st2nd3rdAdjuvant1 TAM TAMTAMTAMOVABLTamoxifenIndications in Breast Cancer三苯氧胺三苯氧胺 乳癌内分泌治疗不可动摇地位！？乳癌内分泌治疗不可动摇地位！？现代乳癌内分泌治疗新方法第13页Survival DataAnastrozole/MAMedian time to death(months)2 year survival rate(%)P Anastrozole is=Exemestane is?Neoadjuvant Letrozole is Adjuvant？Anastrozole 现代乳癌内分泌治疗新方法第23页MilestonesActivated1996Planned accrual9366Accrual to dateClosed 1999 Ongoing AI Adjuvant Trials:ATAC(Anastrozole)Trialists Group TA.Trialists Group TA.Br J Cancer.;85:317.;85:317.RANDOMIZESurgeryTamoxifen 20 mg odAnastrozole 1 mg odTamoxifen 20 mg odAnastrozole 1 mg od5 yearsDFS/OS现代乳癌内分泌治疗新方法第24页KaplanMeier Curves of KaplanMeier Curves of Disease-free Survival in ITT PopulationDisease-free Survival in ITT PopulationCurves truncated at 42 monthsHR95.2%CIp-valueAN vs TAM0.830.710.960.0129Comb vs TAM1.020.881.180.7718TamoxifenAnastrozoleCombinationTime to event(months)Proportion event free(%)Time to event(months)Proportion event free(%)08085909510006121824303642现代乳癌内分泌治疗新方法第25页KaplanMeier Curves of Disease-free Survivalin Receptor-positive PopulationCurves truncated at 42 monthsHR95.2%CIp-valueAN vs TAM0.780.650.930.0054Comb vs TAM1.020.871.210.7786Time to event(months)Proportion event free(%)TamoxifenAnastrozoleCombination08085909510006121824303642现代乳癌内分泌治疗新方法第26页Predefined adverse events*Hot flushesA Arimidex T Tamoxifen C Combination 1060TC1229 1243A%patientsA vs TC vs TA vs C0.791.020.78 OR0.00010.750.0001p value现代乳癌内分泌治疗新方法第27页A vs TC vs TA vs C0.520.940.560.00010.5100102030405060nEndometrial thickness(mm)现代乳癌内分泌治疗新方法第31页Median endometrial thickness024681001224Endometrial thickness(mm)ArimidexTamoxifenCombinationTime(months)现代乳癌内分泌治疗新方法第32页A vs TC vs TA vs C0.230.460.500.020.110.51 ORp valueATCA,Arimidex;C,combination;T,tamoxifen3136%patientsPredefined adverse eventsEndometrial cancer现代乳癌内分泌治疗新方法第33页ATAC SummaryAnastrozole is superior to tamoxifen in terms of:Disease-free survival in:Overall population(HR=0.83)Receptor-positive patients(HR=0.78)Incidence of contralateral breast cancer in:Overall population(OR=0.42)现代乳癌内分泌治疗新方法第34页ConclusionsAnastrozole is the first and only AI to show superior efficacy and improved tolerability compared with tamoxifen in the treatment of EBCOverall risk-benefit assessment supports anastrozole becoming the future adjuvant treatment of choice in postmenopausal womenAnastrozole also shows promise for the chemoprevention of breast cancer现代乳癌内分泌治疗新方法第35页Analysis of the Incidence of New(Contralateral)Breast Primaries Time to first contralateral new primary(months)0612182430364209899100Proportion without CL BCa(%)AnastrozoleTamoxifenCombinationOR95%CIp-valueAN vs TAM0.420.220.790.0068Comb vs TAM0.840.511.40 0.5132现代乳癌内分泌治疗新方法第36页Arimidex(Anastrozole)in Breast cancer prevention:Design of IBIS II and data from ATAC现代乳癌内分泌治疗新方法第37页Why use an Aromatase Inhibitor?At least as effective as tamoxifen in ABCATAC trial provides early warning on side effectsATAC trial provides efficacy data in early breast cancer at all endpoints;striking reduction in contralateral breast cancer eventsVery low side-effect profile 现代乳癌内分泌治疗新方法第38页ATAC:incidence of new(contralateral)breast primaries in ITT population9 invasive05101520253035Tamoxifen(n=3116)Arimidex(n=3125)Combination(n=3125)5 DCIS3 DCIS23invasive5 DCIS30 invasiveNo.casesArimidex vs tamoxifen OR 0.42;95%CI 0.22,0.79;p=0.007Combination vs tamoxifen OR 0.84;95%CI 0.51,1.40;p=0.51现代乳癌内分泌治疗新方法第39页Women-years of follow-up per arm 3100 x 2.8=8600 Rate of contralateral tumours in womennot treated with tamoxifen(women-years)Expected contralateral tumoursObserved on tamoxifen46%reductionObserved on Arimidex77%REDUCTIONATAC:projected contralateral tumour reduction rate for Arimidex7/1000613314现代乳癌内分泌治疗新方法第40页IBIS I Tamoxifen in preventionBreast cancer incidence is reduced by 32%101(placebo)vs 69(TAM)OR 0.68 p=0.01现代乳癌内分泌治疗新方法第41页IBIS II:PreventionHigh-risk postmenopausal women,aged 40-70 years2-arm trial for high-risk patients5-year treatment,placebo controlledN=6000 high-risk patientsRandomizationArimidex1 mgPlacebo现代乳癌内分泌治疗新方法第42页IBIS II:DCISWomen,aged 40-70 years,who have had DCIS diagnosed within the previous 6 months2-arm trial(no placebo arm)5-year treatment,2 tablets/day N=4000N=4000RandomizationArimidex1 mgTamoxifen20 mg现代乳癌内分泌治疗新方法第43页NSABPNSABP centres:USA and Canada Double-blind randomized studyPostmenopausal (n=3000)Start date:Q4 Randomize1:15 years anastrozole1 mg od 5 years tamoxifen20 mg od现代乳癌内分泌治疗新方法第44页 Prevention DCIS/Neoadj5 yearsMetastaticDisease AI 1st2nd3rdAIAI AdjuvantTAM TAMTAMTAM1Arimidex in Breast CancerMAMAAI绝经后绝经后绝经前绝经前？AIAI现代乳癌内分泌治疗新方法第45页绝经前乳癌内分泌治疗绝经前乳癌内分泌治疗 卵巢去势 绝经前 抗芳香化酶 瑞宁得（阿那曲唑）瑞宁得（阿那曲唑）氟隆氟隆 依西美坦依西美坦绝经后现代乳癌内分泌治疗新方法第46页卵巢切除加口服依西美坦卵巢切除加口服依西美坦治疗绝经前乳腺癌骨转移长久缓解治疗绝经前乳腺癌骨转移长久缓解 霍秀兰，女，41岁，住院号50982.2 多发骨转移，左锁上淋巴结转移，穿刺活检ER(+)PR(+)Her-2(+).4.6因患者未停经，给予双侧卵巢切除术，1月后骨痛症状改进，骨质修复；.5.11口服依西美坦，.6.6 骨痛深入减轻，疗效评价：PR 现代乳癌内分泌治疗新方法第47页Zoladex 诺雷得诺雷得 用于绝经前乳腺癌患者治疗用于绝经前乳腺癌患者治疗现代乳癌内分泌治疗新方法第48页Zoladex与卵巢切除术与卵巢切除术治疗复发转移乳癌效果比较治疗复发转移乳癌效果比较现代乳癌内分泌治疗新方法第49页Zoladex 3.6mg 用于绝经前进展期乳腺癌II期临床试验资料起源于 29 个 II期临床试验(n=228)CR+PR=36.4%中位缓解间期 =22 周耐受性好，未出现因不良反应退出抑制雌激素药理作用是常见面部潮红(75.9%)性欲减退(47.4%)现代乳癌内分泌治疗新方法第50页Klijn JGM,et al.J Clin Oncol;19:34353.变量变量LHRH类似物类似物LHRH 类似物类似物+Tamoxifen相对相对危险度危险度p 值值OR(CR+PR)30%39%0.670.03PFS(中位中位)5.4月月8.7 月月0.70 Zoladex Arimidex TAM Zoladex+Arimidex 诺雷得+瑞宁得绝经前乳癌内分泌治疗绝经前乳癌内分泌治疗 现代乳癌内分泌治疗新方法第53页 诺雷德诺雷德+瑞宁得治疗绝经前患者瑞宁得治疗绝经前患者田田XX，女，女，39岁，住院号岁，住院号53056.10 多发骨转移、肝转移多发骨转移、肝转移ER(+)PR(+)Her-2(+).11.1 Herceptin治疗治疗 PD.01.3.TA化疗化疗2周期周期 SD 2 mo.3.28 诺雷德诺雷德+瑞宁得瑞宁得 PR 症状显著改进，生活自理，症状显著改进，生活自理，KPS 90分分 B超示肝脏病灶显著缩小超示肝脏病灶显著缩小 X光片示骨病灶好转光片示骨病灶好转 至至11月疾病依然处于缓解期月疾病依然处于缓解期 现代乳癌内分泌治疗新方法第54页A Randomized Trial of Zoladex+TAM vsZoladex+Arimidexin per/perimenopausal patients with hormone dependent ABC现代乳癌内分泌治疗新方法第55页Zoladex+TAM vs Zoladex+Arimidexin per/perimenopausal ABC patients 1999.1-.12119 cases ABCFirst lineER(+)Zoladex 3.6mg/28d +TAM 20mg/dZoladex 3.6mg/28d +Arimidex 1mg/d现代乳癌内分泌治疗新方法第56页Zoladex+Arimidex vs Zoladex+TAM in pre/perimenopausal ABC patients Zoladex+Arimidex Zoladex+TAM CR+PR 80%53%Median durationof CB 12.1 months 8.3 months Median time toDeath 18.9 months 14.3 months现代乳癌内分泌治疗新方法第57页 Zoladex+Arimidex is effcient and well toleratedshould be considered for first line therapy in per/perimenopausal women with hormone dependent ABC Milla-Santos,SAB,Dec现代乳癌内分泌治疗新方法第58页Overview of LHRHa in Breast Cancer Adjuvant Therapy Benefits of Reversible Ovarian Ablation现代乳癌内分泌治疗新方法第59页1.EBCTCG.Lancet 1996;348:118996.2.Brincker H,et al.J Clin Oncol 1987;5:17718.Zoladex 用于辅助治疗 Zoladex 3.6mg单用或与 tamoxifen适用在晚期乳腺癌治疗中显示其良好疗效和耐受性EBCTCG 1996年资料明确了绝经前早期乳腺癌治疗中卵巢去势延长生存作用现代乳癌内分泌治疗新方法第60页Estimation of the hazard ratio for relapse between women with drug-induced amenorrhea(group A)and those without(group B)10 published studies(1995)Results:1.In 9/10 studies RFS longer in group A than in group B NB Bonadonnas CMF study:20-year RFS=39%vs 30%(=22%reduction;p=NS)2.Mean hazard ratio:0.56 (0.39-0.86)*del Mastro et al.N Engl J Med 1995;333:596-597Conclusion:Drug-induced amenorrhea is associated with a 44%reduction in the rate of relapse现代乳癌内分泌治疗新方法第61页*Aebi et al.Lancet;355:1869-1874Impact of chemotherapy-induced amenorrhea(AM+)in the adjuvant setting by age*IBCSG studies I,II,V,VII:treatment with chemotherapy onlyER+AM-ER+AM+ER-AM-ER-AM+8000 patientsDesignConferring additional benefit when added to standard treatmentPotential replacement for chemotherapy现代乳癌内分泌治疗新方法第63页ZEBRA试验试验(Zoladex Early Breast Cancer Research Association)“诺雷德诺雷德”（戈舍瑞林）（戈舍瑞林）与与CMF辅助治疗辅助治疗绝经期前和更年期妇女乳腺癌疗效比较绝经期前和更年期妇女乳腺癌疗效比较现代乳癌内分泌治疗新方法第64页ZEBRA 试验设计手术手术 放疗放疗Zoladex 3.6mg 1/28天天 2年年绝经前绝经前/围绝经期围绝经期 LNM()早期乳腺癌早期乳腺癌 年纪年纪 50 岁岁随访随访CMF 1/28天天 x 6程程随机化随机化1:1 (开放开放 多中心多中心)肿瘤复发肿瘤复发死亡死亡死亡死亡现代乳癌内分泌治疗新方法第65页ZEBRA 临床试验结论Zoladex 在受体阳性病例与 CMF 疗效相等ER水平检测对治疗起关键作用Zoladex较之CMF 有更小不良反应Zoladex单药治疗 是对ER+、淋巴结阳性、绝经前/围绝经期早期乳腺癌 CMF化疗之外又一治疗选择现代乳癌内分泌治疗新方法第66页CMF x 6 Zoladex 3.6mg/28 天天x 3年年+TAM 20mg/天天x 5 年年随机分组随机分组 1:1绝经前绝经前ER+和和/或或 PgR+ve乳腺癌乳腺癌Jakesz R,et al.Breast Cancer Res Treat 1999;57:25,Abstr 2.Jakesz R,et al.Eur J Surg Oncol;26:281,Abstr 110.l1,045 可评定病例可评定病例l淋巴结淋巴结+/ABCSG AC05 临床试验奥地利乳腺癌辅助治疗试验 现代乳癌内分泌治疗新方法第67页ABCSG AC05临床试验结果 Zoladex 3.6mg 加用TAM组DFS显著提升总生存率亦有提升趋势 Zoladex 3.6mg加用TAM较CMF 对绝经前受体阳性乳腺癌辅助治疗更为有效Jakesz R,et al.Breast Cancer Res Treat 1999;57:25,Abstr 2.Jakesz R,et al.Eur J Surg Oncol;26:281,Abstr 110.现代乳癌内分泌治疗新方法第68页l2,648 例例l随机化试验随机化试验l淋巴结淋巴结+/-l不论不论ER 状态状态l标准治疗标准治疗=放疗放疗 化疗化疗 tamoxifen标准治疗标准治疗手术手术.Zoladex 3.6mg/28 天天 2 年年Tamoxifen 20mg/天天 2 年年Zoladex 3.6mg/28 天天+TAM 2 年年 无深入治疗无深入治疗 Houghton J,et al.ASCO;19:93a,Abstr 359.Zoladex 用于绝经前患者(ZIPP)现代乳癌内分泌治疗新方法第69页ZIPP结果乳癌术后在标准治疗中加用 Zoladex DFS显著改进显著改进(HR=0.77 p0.001)提升生存趋势提升生存趋势(HR=0.78 p=0.08)对侧乳腺癌发生率降低对侧乳腺癌发生率降低(HR=0.60 p=0.05)ER+ve患者较患者较ERve 或不详患者更有益或不详患者更有益Houghton J,et al.ASCO;19:93a,Abstr 359.Baum M.Breast Cancer Res Treat 1999;57:30,Abstr 24.现代乳癌内分泌治疗新方法第70页INT-0101 ECOG/SWOG 临床试验 手术手术CAF x 6随机化随机化 1:1:1CAF x 6 Zoladex x 5 年年CAF x 6 Zoladex+TAM x 5 年年Davidson NE,et al.Breast 1999;8:2323,Abstr 069.多中心试验1,504 例合格病例绝经前淋巴结+、受体+比较局部复发率/DFS/生存率 现代乳癌内分泌治疗新方法第71页INT-0101:5-Year 结果*CAF+Zoladex vs CAF alone#CAF+Zoladex+TAM vs CAF+Zoladex 3.6mg+当前尚无统计分析发表当前尚无统计分析发表 NS=无意义无意义CAF CAF+Zoladex CAF+Zoladex+TAM (n=494)(n=502)(n=507)DFS(%)67 70(p=0.06)*77(p0.01)#40岁患者岁患者DFS(%)54 65+72+总体生存率总体生存率 85 86(NS)86(NS)Kuter I.Oncologist 1999;4:299308.Davidson NE,et al.Breast 1999;8:2323,Abstr 069.现代乳癌内分泌治疗新方法第72页 Zoladex 辅助治疗试验结果总结 研究研究治疗治疗疾病基本情况疾病基本情况DFS 结果结果 ZEBRAZOL vs.CMFLNM+ZOL对对 ER+患者与患者与 CMF等效等效(n=1,640)74%ER+AC05ZOL+TAMER/PR+ZOL+TAM 较较CMF更有效更有效(n=1,045)vs.CMF GROCTATAM+Ov.Supp.ER+NS(n=244)vs.CMFINT-0101CAF vs.LNM+CAFZT vs.CAFZ更有效更有效(n=1,504)CAF+ZOL vs.ER/PR+CAF+ZOL+TAM CAFZ vs.CAF更有效趋势更有效趋势 但无统计学差异但无统计学差异(p=0.06)ZIPP ZOL+标准治疗标准治疗 70%ER+标准治疗标准治疗 ZOL (n=2,648)vs.较单用标准治疗更有效较单用标准治疗更有效 标准治疗标准治疗*标准治疗标准治疗=+/-放疗放疗+/-化疗化疗+/-tamoxifen 现代乳癌内分泌治疗新方法第73页结结 论论Zoladex对绝经前受体阳性早期乳癌辅助治疗有效 Zoladex单药或联合TAM疗效不比化疗效果差在标准化疗基础上加 ZoladexTAM效果更加好 Zoladex可作为可作为 绝经前、受体阳性早期乳癌辅助治疗绝经前、受体阳性早期乳癌辅助治疗 现代乳癌内分泌治疗新方法第74页N-low riskN-average/high riskN+TAM or none1.Ov abl+TAM CT2.CT+TAM Ov abl3.TAM4.Ov abl1.CT+TAM Ov abl2.Ov abl+TAM CTTAM or none1.TAM 2.CT+TAM1.CT+TAM 2.TAM ER+veOv abl,oophorectomy or GnRH analogue;CT,chemotherapyGuidelines for adjuvant therapyof breast cancerSt Gallen Risk groupER-vePremenopausalPostmenopausalNACT CT 现代乳癌内分泌治疗新方法第75页QuestionsDoes endocrine therapy add to chemotherapy?Answer:yesDoes chemotherapy add to optimal endocrine therapy?Answer:In premenopausal ER-positive breast cancer:unknownprobably no or only minor extra benefitreplacement of tamoxifen by an aromataseinhibitor might improve optimal endocrine therapy现代乳癌内分泌治疗新方法第76页Study design BOOG1 Multicentre,open,randomized trial in high-risk ER-positive primary breast cancerMain question:does chemotherapy(CT)add to optimal endocrine therapy in steroid receptor-positive patients?Randomizationoptimal endocrine therapy RToptimal endocrine therapy+standard CT RTStratification:nodal status(N0,N1-4,N4)age categories(40 vs 40 years)cDNA microarray profileBCT vs mastectomy现代乳癌内分泌治疗新方法第77页Study design BOOG1(2)Zoladex+Arimidex(5 yrs)Zoladex+Arimidex(5 yrs)+CT (5 x FEC)R现代乳癌内分泌治疗新方法第78页Ongoing International Clinical TrialArimidexvsArimidex+Herceptinfor ER/PR positive and Her-2 overexpression Advanced Breast Cancer现代乳癌内分泌治疗新方法第79页瑞宁得用于瑞宁得用于绝经后绝经后复发转移乳癌复发转移乳癌 79 岁 女性1996年左乳癌 T2N1M0 术后CMF化疗1998年右乳癌 T2N0M0 ER(+)PR(+)TAM 10mg/d年11月肺部结节影（M?）ECT示第六肋浓聚但X片未见骨质破坏Next:瑞宁得 1mg 1/d .10-现代乳癌内分泌治疗新方法第80页瑞宁得用于复发转移乳癌瑞宁得用于复发转移乳癌+诺雷得诺雷得 用于用于绝经前患者绝经前患者34 yrs 女性CAF辅助治疗后肝转移、骨转移ER(+)PR(+)Her-2(+)Herceptin PDTaxotere+Carboplatin 2 周期 SDER(+)PR(+).1-Zoladex+Arimidex疗效：PR 治疗中（.12）现代乳癌内分泌治疗新方法第81页瑞宁得用于高危乳癌术后辅助治疗瑞宁得用于高危乳癌术后辅助治疗65 岁 女性年 左乳改良根治术 T3N2M0 LNM 10/10 ER(+)PR(+)Her-2(+)因冠心病、糖尿病等术后3个月未化疗辅助治疗:芳香化酶抑制剂 现代乳癌内分泌治疗新方法第82页瑞宁得瑞宁得+诺雷得诺雷得绝经前乳癌辅助治疗绝经前乳癌辅助治疗绝经前T2N1M0 LNM 2/5 ER(+)PR(+)Her-2(+)CAF 辅助化疗 2 个周期化疗期间肺结核加重下步治疗：停化疗停化疗抗结核治疗抗结核治疗诺雷得诺雷得+瑞宁得瑞宁得 辅助内分泌治疗辅助内分泌治疗现代乳癌内分泌治疗新方法第83页 Prevention DCIS/Neoadj5 yearsMetastaticDisease AI 1st2nd3rdAIAI AdjuvantAI AITAM TAMTAMTAM?1AI 芳香化酶抑制剂现实状况和未芳香化酶抑制剂现实状况和未来来绝经前绝经前 诺雷得诺雷得 诺雷得诺雷得+瑞宁得瑞宁得现代乳癌内分泌治疗新方法第84页乳癌内分泌治疗方向乳癌内分泌治疗方向新药品新药品新指征新指征（解救解救-新辅助新辅助-辅助辅助-预防预防）新联合新联合内分泌药品联合（内分泌药品联合（LHRHa+Ais）辅助治疗与化疗辅助治疗与化疗(CAF-T)序贯联合序贯联合 与生物治疗（与生物治疗（Herceptin）联合联合现代乳癌内分泌治疗新方法第85页乳癌全身治疗科学合理应用乳癌全身治疗科学合理应用内分泌治疗内分泌治疗化化 疗疗生物治疗生物治疗现代乳癌内分泌治疗新方法第86页