乳腺癌內(nèi)分泌治療的新思路和臨床實踐培訓(xùn)課件

1、乳腺癌內(nèi)分泌治療的新思路和臨床實踐乳腺癌內(nèi)分泌治療的新思路和臨床實踐乳癌的治療手段Surgery 手術(shù)Radiation therapy 放療Chemotherapy 化療Hormone therapy 內(nèi)分泌治療Biotherapy 生物治療New therapies 新的治療乳腺癌內(nèi)分泌治療的新思路和臨床實踐2乳癌的治療手段Surgery 乳癌內(nèi)分泌治療的發(fā)展1970198019902000TamoxifenTamoxifenMAAG新的芳香化酶抑制劑Exemestane /MA新的芳香化酶抑制劑Tamoxifenpure A.E. ? MAIIIIIIIIIIIIIII乳腺癌內(nèi)分泌治療的

2、新思路和臨床實踐3乳癌內(nèi)分泌治療的發(fā)展1970198019902000TamoHormone Therapy Response Rate (%) in Different Receptor Status乳腺癌內(nèi)分泌治療的新思路和臨床實踐4Hormone Therapy Response Rate Survival by Response Arimidex 1 mg02040608010001234CR or PRStable 24 wksProgressionYears from Randomisation% Survival 乳腺癌內(nèi)分泌治療的新思路和臨床實踐5Survival by Res

3、ponse ArimidexMAAG Prevention DCIS/Neoadj 5 yearsMetastaticDisease 1st2nd3rdAdjuvant TAM TAMTAMTAMOVABL三苯氧胺 （TAM) 最重要的乳癌內(nèi)分泌治療藥物乳腺癌內(nèi)分泌治療的新思路和臨床實踐6MA Prevention DCIS/5 yearsMTamoxifen for 5 Years vs No TreatmentPercentYearsER+85.276.168.273.762.754.911.5 (SE 0.9)13.4 (SE 1.1)13.4 (SE 1.4)68.2%54.9%020

4、406080100051015vsRecurrencesBreast Deaths020406080100051015ER+73.0%64.0%91.480.973.087.873.264.03.6 (SE 0.7)7.8 (SE 1.0)9.0 (SE 1.4)vsYearsPercent乳腺癌內(nèi)分泌治療的新思路和臨床實踐7Tamoxifen for 5 Years vs No TTamoxifen Adjuvant Therapy for EBC輔助內(nèi)分泌治療的決定因素是激素受體狀況ER陽性效果最好 乳腺癌內(nèi)分泌治療的新思路和臨床實踐8Tamoxifen Adjuvant Therapy

5、forTamoxifen Adjuvant Therapy for EBC合適的TAM服藥時間為5年乳腺癌內(nèi)分泌治療的新思路和臨床實踐9Tamoxifen Adjuvant Therapy forTamoxifen Adjuvant Therapy for EBC ER陽性無論年齡大小都可用TAM乳腺癌內(nèi)分泌治療的新思路和臨床實踐10Tamoxifen Adjuvant Therapy forTamoxifen Adjuvant Therapy for EBC降低對側(cè)乳癌發(fā)生增加子宮內(nèi)膜癌的風(fēng)險乳腺癌內(nèi)分泌治療的新思路和臨床實踐11Tamoxifen Adjuvant Therapy forT

6、amoxifen Adjuvant Therapy for EBC ER陽性TAM和化療合用比單用TAM更有效CAF與TAM 序貫合用比同時效果更好 乳腺癌內(nèi)分泌治療的新思路和臨床實踐12Tamoxifen Adjuvant Therapy forMAAG Prevention DCIS/Neoadj 5 yearsMetastaticDisease 1st2nd3rdAdjuvant1 TAM TAMTAMTAMOVABLTamoxifenIndications in Breast Cancer三苯氧胺 乳癌內(nèi)分泌治療不可動搖的地位??？乳腺癌內(nèi)分泌治療的新思路和臨床實踐13MA Preven

7、tion DCIS/5 yearsMSurvival DataAnastrozole / MAMedian time to death(months)2 year survival rate (%)P Anastrozole is = Exemestane is? Neoadjuvant Letrozole is Adjuvant ？Anastrozole 乳腺癌內(nèi)分泌治療的新思路和臨床實踐23The Gold Standard TamoxifenFirMilestonesActivated1996Planned accrual9366Accrual to dateClosed 1999 On

8、going AI Adjuvant Trials: ATAC (Anastrozole)Trialists Group TA. Br J Cancer. 2001;85:317.RANDOM IZESurgeryTamoxifen 20 mg odAnastrozole 1 mg odTamoxifen 20 mg odAnastrozole 1 mg od5 yearsDFS/OS乳腺癌內(nèi)分泌治療的新思路和臨床實踐24MilestonesOngoing AI Adjuvant KaplanMeier Curves of Disease-free Survival in ITT Populat

9、ionCurves 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乳腺癌內(nèi)分泌治療的新思路和臨床實踐25KaplanMeier Curves of Dis

10、easKaplanMeier 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乳腺癌內(nèi)分泌治療的新思路和臨床實踐

11、26KaplanMeier Curves of DiseasePredefined adverse events*Hot flushesA Arimidex T Tamoxifen C Combination 1060TC12291243A% patientsA vs TC vs TA vs C0.791.020.78 OR0.00010.750.0001p value乳腺癌內(nèi)分泌治療的新思路和臨床實踐27Predefined adverse events*HotA vs TC vs TA vs C0.520.940.560.00010.50.0001ORp valueATCA, Arimid

12、ex; C, combination; T, tamoxifen138253238% patientsPredefined adverse eventsVaginal bleeding乳腺癌內(nèi)分泌治療的新思路和臨床實踐28A vs T0.52100102030405060nEndometrial thickness (mm)乳腺癌內(nèi)分泌治療的新思路和臨床實踐31Baseline Ultrasound12345678910Median endometrial thickness024681001224Endometrial thickness (mm)ArimidexTamoxifenCombi

13、nationTime (months)乳腺癌內(nèi)分泌治療的新思路和臨床實踐32Median endometrial thickness02A vs TC vs TA vs C0.230.460.500.020.110.51 ORp valueATCA, Arimidex; C, combination; T, tamoxifen3136% patientsPredefined adverse eventsEndometrial cancer乳腺癌內(nèi)分泌治療的新思路和臨床實踐33A vs T0.230.02 ORp vaATAC SummaryAnastrozole is superior to

14、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)乳腺癌內(nèi)分泌治療的新思路和臨床實踐34ATAC SummaryAnastrozole is suConclusionsAnastrozole is the first and only AI to show superior eff

15、icacy 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乳腺癌內(nèi)分泌治療的新思路和臨床實踐35Conclu

16、sionsAnastrozole is the 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乳腺癌內(nèi)分泌治

17、療的新思路和臨床實踐36Analysis of the Incidence of NArimidex (Anastrozole) in Breast cancer prevention: Design of IBIS II and data from ATAC乳腺癌內(nèi)分泌治療的新思路和臨床實踐37Arimidex (Anastrozole) in BreWhy use an Aromatase Inhibitor?At least as effective as tamoxifen in ABCATAC trial provides early warning on side effectsA

18、TAC trial provides efficacy data in early breast cancer at all endpoints; striking reduction in contralateral breast cancer eventsVery low side-effect profile 乳腺癌內(nèi)分泌治療的新思路和臨床實踐38Why use an Aromatase InhibitoATAC: incidence of new (contralateral) breast primaries in ITT population9 invasive0510152025

19、3035Tamoxifen(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乳腺癌內(nèi)分泌治療的新思路和臨床實踐39ATAC: incidence of new (contraWomen-years of follow-up per ar

20、m 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乳腺癌內(nèi)分泌治療的新思路和臨床實踐40Women-year

21、s of follow-up per aIBIS I Tamoxifen in preventionBreast cancer incidence is reduced by 32%101 ( placebo ) vs 69 ( TAM ) OR 0.68 p=0.01乳腺癌內(nèi)分泌治療的新思路和臨床實踐41IBIS I Tamoxifen in preventioIBIS II: PreventionHigh-risk postmenopausal women, aged 40-70 years2-arm trial for high-risk patients5-year treatment

22、, placebo controlledN = 6000 high-risk patientsRandomizationArimidex1 mgPlacebo乳腺癌內(nèi)分泌治療的新思路和臨床實踐42IBIS II: PreventionHigh-risk pIBIS 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 = 4000Randomizat

23、ionArimidex1 mgTamoxifen20 mg乳腺癌內(nèi)分泌治療的新思路和臨床實踐43IBIS II: DCISWomen, aged 40-70NSABPNSABP centres: USA and Canada Double-blind randomized studyPostmenopausal (n=3000)Start date: Q4 2002Randomize1:15 years anastrozole1 mg od 5 years tamoxifen20 mg od乳腺癌內(nèi)分泌治療的新思路和臨床實踐44NSABPStart date: Q4 2002Random Pr

24、evention DCIS/ Neoadj5 yearsMetastaticDisease AI 1st2nd3rdAIAI AdjuvantTAM TAMTAMTAM1Arimidex in Breast CancerMAAI絕經(jīng)后絕經(jīng)前 ？AIAI乳腺癌內(nèi)分泌治療的新思路和臨床實踐45 Prevention DCIS/5 yearsMet絕經(jīng)前乳癌內(nèi)分泌治療 卵巢去勢 絕經(jīng)前 抗芳香化酶 瑞寧得（阿那曲唑）氟隆 依西美坦絕經(jīng)后乳腺癌內(nèi)分泌治療的新思路和臨床實踐46絕經(jīng)前乳癌內(nèi)分泌治療絕經(jīng)前絕經(jīng)后乳腺癌內(nèi)分泌治療的新思路和臨卵巢切除加口服依西美坦治療絕經(jīng)前乳腺癌骨轉(zhuǎn)移長期緩解 霍秀蘭，女，4

25、1歲，住院號50982 2001.2 多發(fā)骨轉(zhuǎn)移，左鎖上淋巴結(jié)轉(zhuǎn)移， 穿刺活檢ER(+) PR(+) Her-2(+) 2001.4.6因患者未停經(jīng)，予以雙側(cè)卵巢切除術(shù)，1月后骨痛癥狀改善，骨質(zhì)修復(fù)； 2001.5.11口服依西美坦，2001.6.6 骨痛進(jìn)一步減輕，療效評價：PR 乳腺癌內(nèi)分泌治療的新思路和臨床實踐47卵巢切除加口服依西美坦治療絕經(jīng)前乳腺癌骨轉(zhuǎn)移長期緩解 霍秀Zoladex 諾雷得 用于絕經(jīng)前乳腺癌患者的治療乳腺癌內(nèi)分泌治療的新思路和臨床實踐48Zoladex 諾雷得 用于絕經(jīng)前乳腺癌患者的治療乳Zoladex與卵巢切除術(shù)治療復(fù)發(fā)轉(zhuǎn)移乳癌效果比較乳腺癌內(nèi)分泌治療的新思路和臨床

26、實踐49Zoladex與卵巢切除術(shù)治療復(fù)發(fā)轉(zhuǎn)移乳癌效果比較乳腺癌內(nèi)Zoladex 3.6mg 用于絕經(jīng)前進(jìn)展期乳腺癌II期臨床試驗資料來源于 29 個 II期臨床試驗 (n=228 )CR+PR = 36.4%中位緩解間期 = 22 周耐受性好，未出現(xiàn)因不良反應(yīng)退出抑制雌激素的藥理作用是常見的面部潮紅 ( 75.9%) 性欲減退 ( 47.4% )乳腺癌內(nèi)分泌治療的新思路和臨床實踐50Zoladex 3.6mg 用于絕經(jīng)前進(jìn)展期乳腺癌II期臨Klijn JGM, et al. J Clin Oncol 2001; 19: 34353.變量LHRH類似物L(fēng)HRH 類似物 + Tamoxifen相

27、對危險度p 值OR (CR+PR)30%39%0.670.03PFS (中位)5.4月8.7 月0.70 Zoladex Arimidex TAM Zoladex + Arimidex 諾雷得 + 瑞寧得絕經(jīng)前乳癌內(nèi)分泌治療 乳腺癌內(nèi)分泌治療的新思路和臨床實踐53 Zoladex 諾雷德 + 瑞寧得治療絕經(jīng)前患者田XX，女，39歲，住院號53056 2001.10 多發(fā)骨轉(zhuǎn)移、肝轉(zhuǎn)移ER (+) PR (+) Her-2 (+)2001.11.2002.1 Herceptin治療 PD 2002.01. 2002.3. TA化療2周期 SD 2 mo 2002. 3.28 諾雷德 + 瑞寧得

28、PR 癥狀明顯改善，生活自理，KPS 90分 B超示肝臟病灶明顯縮小 X光片示骨病灶好轉(zhuǎn) 至2002年11月疾病依然處于緩解期 乳腺癌內(nèi)分泌治療的新思路和臨床實踐54 諾雷德 + 瑞寧得治療絕經(jīng)前患者田XX，女，39歲，住院號A Randomized Trial of Zoladex + TAM vsZoladex + Arimidexin per/perimenopausal patients with hormone dependent ABC乳腺癌內(nèi)分泌治療的新思路和臨床實踐55A Randomized Trial of ZoladeZoladex + TAM vs Zoladex +

29、Arimidexin per/perimenopausal ABC patients 1999.1 - 2001.12119 cases ABCFirst lineER (+)Zoladex 3.6mg / 28d + TAM 20mg/dZoladex 3.6mg / 28d + Arimidex 1mg/d乳腺癌內(nèi)分泌治療的新思路和臨床實踐56Zoladex + TAM vs Zoladex + Zoladex + Arimidex vs Zoladex + TAM in pre/perimenopausal ABC patients Zoladex + Arimidex Zoladex

30、+ TAM CR + PR 80 % 53 %Median durationof CB 12.1 months 8.3 months Median time toDeath 18.9 months 14.3 months乳腺癌內(nèi)分泌治療的新思路和臨床實踐57Zoladex + Arimidex vs Zoladex Zoladex + Arimidex is effcient and well toleratedshould be considered for first line therapy in per/perimenopausal women with hormone depende

31、nt ABC Milla-Santos, SAB 2002,Dec乳腺癌內(nèi)分泌治療的新思路和臨床實踐58 Zoladex + Arimidex is effciOverview of LHRHa in Breast Cancer Adjuvant Therapy Benefits of Reversible Ovarian Ablation乳腺癌內(nèi)分泌治療的新思路和臨床實踐59Overview of LHRHa in Breast C1. EBCTCG. Lancet 1996; 348: 118996.2. Brincker H, et al. J Clin Oncol 1987; 5: 1

32、7718.Zoladex 用于輔助治療 Zoladex 3.6mg單用或與 tamoxifen合用在晚期乳腺癌治療中顯示其良好的療效和耐受性EBCTCG 1996年資料明確了絕經(jīng)前早期乳腺癌治療中卵巢去勢延長生存的作用乳腺癌內(nèi)分泌治療的新思路和臨床實踐601. EBCTCG. Lancet 1996; 348: 1Estimation of the hazard ratio for relapse between women with drug-induced amenorrhea ( group A ) and those without ( group B )10 published st

33、udies (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% reduc

34、tion in the rate of relapse乳腺癌內(nèi)分泌治療的新思路和臨床實踐61Estimation of the hazard ratio*Aebi et al. Lancet 2000;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 patientsDesi

35、gnConferring additional benefit when added to standard treatmentPotential replacement for chemotherapy乳腺癌內(nèi)分泌治療的新思路和臨床實踐63Zoladex Trials in PremenopauZEBRA試驗( Zoladex Early Breast Cancer Research Association )“諾雷德”（戈舍瑞林）與CMF輔助治療絕經(jīng)期前和更年期婦女乳腺癌的療效比較乳腺癌內(nèi)分泌治療的新思路和臨床實踐64ZEBRA試驗( Zoladex Early BreZEBRA 試驗設(shè)計

36、手術(shù) 放療Zoladex 3.6mg 1 / 28天 2年絕經(jīng)前 / 圍絕經(jīng)期 LNM() 早期乳腺癌 年齡 50 歲隨訪CMF 1 / 28天 x 6程隨機化1:1 (開放 多中心)腫瘤復(fù)發(fā)死亡死亡乳腺癌內(nèi)分泌治療的新思路和臨床實踐65ZEBRA 試驗設(shè)計手術(shù) 放療Zoladex 3.ZEBRA 臨床試驗結(jié)論Zoladex 在受體陽性病例與 CMF 療效相等ER水平檢測對治療起關(guān)鍵作用Zoladex較之CMF 有更小的不良反應(yīng)Zoladex單藥治療 是對ER+、淋巴結(jié)陽性、絕經(jīng)前/圍絕經(jīng)期早期乳腺癌 CMF化療之外的又一治療選擇乳腺癌內(nèi)分泌治療的新思路和臨床實踐66ZEBRA 臨床試驗結(jié)論Z

37、oladex 在受體陽性病例與 CCMF x 6 Zoladex 3.6mg/28 天x 3年 +TAM 20mg/天x 5 年隨機分組 1:1絕經(jīng)前ER+和/或 PgR+ve乳腺癌Jakesz R, et al. Breast Cancer Res Treat 1999; 57: 25, Abstr 2.Jakesz R, et al. Eur J Surg Oncol 2000; 26: 281, Abstr 110.1,045 可評估病例淋巴結(jié) + / ABCSG AC05 臨床試驗奧地利乳腺癌輔助治療試驗 乳腺癌內(nèi)分泌治療的新思路和臨床實踐67CMF x 6 Zoladex 3.6mg

38、/28 天xABCSG AC05臨床試驗結(jié)果 Zoladex 3.6mg 加用TAM組DFS顯著提高總生存率亦有提高趨勢 Zoladex 3.6mg加用TAM較CMF 對絕經(jīng)前受體陽性乳腺癌輔助治療更為有效Jakesz R, et al. Breast Cancer Res Treat 1999; 57: 25, Abstr 2.Jakesz R, et al. Eur J Surg Oncol 2000; 26: 281, Abstr 110.乳腺癌內(nèi)分泌治療的新思路和臨床實踐68ABCSG AC05臨床試驗結(jié)果 Zoladex 3.6m2,648 例隨機化試驗淋巴結(jié) + / -無論ER 狀

39、態(tài)標(biāo)準(zhǔn)治療 = 放療 化療 tamoxifen標(biāo)準(zhǔn)治療手術(shù).Zoladex 3.6mg / 28 天 2 年Tamoxifen 20mg / 天2 年Zoladex 3.6mg / 28 天 + TAM 2 年 無進(jìn)一步治療 Houghton J, et al. ASCO 2000; 19: 93a, Abstr 359.Zoladex 用于絕經(jīng)前患者 (ZIPP) 乳腺癌內(nèi)分泌治療的新思路和臨床實踐692,648 例標(biāo)準(zhǔn)治療手術(shù).Zoladex 3.6mg / ZIPP結(jié)果乳癌術(shù)后在標(biāo)準(zhǔn)治療中加用 Zoladex DFS顯著改善 ( HR = 0.77 p0.001)提高生存的趨勢 ( HR

40、=0.78 p=0.08 )對側(cè)乳腺癌發(fā)生率降低 ( HR=0.60 p=0.05 )ER+ve患者較ERve 或不詳?shù)幕颊吒幸鍴oughton J, et al. ASCO 2000; 19: 93a, Abstr 359.Baum M. Breast Cancer Res Treat 1999; 57: 30, Abstr 24.乳腺癌內(nèi)分泌治療的新思路和臨床實踐70ZIPP結(jié)果乳癌術(shù)后在標(biāo)準(zhǔn)治療中加用 Zoladex DINT-0101 ECOG / SWOG 臨床試驗 手術(shù)CAF x 6隨機化 1:1:1CAF x 6 Zoladex x 5 年CAF x 6 Zoladex +TA

41、M x 5 年Davidson NE, et al. Breast 1999; 8: 2323, Abstr 069. 多中心試驗1,504 例合格病例絕經(jīng)前淋巴結(jié)+ 、受體+ 比較局部復(fù)發(fā)率 / DFS / 生存率 乳腺癌內(nèi)分泌治療的新思路和臨床實踐71INT-0101 ECOG / SWOG 臨床試驗 乳腺癌內(nèi)分泌治療的新思路和臨床實踐培訓(xùn)課件 Zoladex 輔助治療試驗結(jié)果總結(jié) 研究治療疾病基本情況DFS 結(jié)果 ZEBRAZOL vs. CMFLNM + ZOL對 ER+ 患者與 CMF等效(n=1,640)74% ER + AC05ZOL + TAMER / PR + ZOL + T

42、AM 較CMF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 (n=1,504)CAF + ZOL vs. ER / PR + CAF + ZOL +TAM CAFZ vs. CAF更有效趨勢 但無統(tǒng)計學(xué)差異 (p=0.06)ZIPP ZOL + 標(biāo)準(zhǔn)治療 70% ER + 標(biāo)準(zhǔn)治療 ZOL (n=2,648) vs. 較單用標(biāo)準(zhǔn)治療更有效 標(biāo)準(zhǔn)治療* 標(biāo)準(zhǔn)治療 = +/-放療 +/-化療 +/- tamoxifen 乳腺癌內(nèi)分泌治療的新思

43、路和臨床實踐73 Zoladex 輔助治療試驗結(jié)果總結(jié) 研究治療疾病基本結(jié) 論Zoladex對絕經(jīng)前受體陽性早期乳癌輔助治療有效 Zoladex單藥或聯(lián)合TAM療效不比化療效果差在標(biāo)準(zhǔn)化療的基礎(chǔ)上加 ZoladexTAM的效果更好 Zoladex可作為 絕經(jīng)前、受體陽性早期乳癌輔助治療 乳腺癌內(nèi)分泌治療的新思路和臨床實踐74結(jié) 論Zoladex對絕經(jīng)前受體陽性早期乳癌輔助治N -low riskN -average/high riskN +TAM or none1. Ov abl + TAM CT2. CT + TAM Ov abl3. TAM4. Ov abl1. CT + TAM Ov a

44、bl2. 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 2001Risk groupER-vePremenopausalPostmenopausalNACT CT 乳腺癌內(nèi)分泌治療的新思路和臨床實踐75N -low riskTAM or noneTAM QuestionsDoes en

45、docrine 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乳腺癌內(nèi)分泌治療的新思路和臨床

46、實踐76QuestionsDoes endocrine therapStudy 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 4