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1、乳癌内分泌治疗新思路和临床实践军事医学科学院307医院乳癌科乳癌的治疗手段 Surgery 手术 Radiation therapy 放疗 Chemotherapy 化疗 Hormone therapy 内分泌治疗 Biotherapy 生物治疗 New therapies 新的治疗乳癌内分泌治疗的发展乳癌内分泌治疗的发展1970198019902000TamoxifenTamoxifenMA AG新的芳香化酶抑制剂新的芳香化酶抑制剂Exemestane / MA新的芳香化酶抑制剂新的芳香化酶抑制剂Tamoxifen pure A.E. ? MAI IIIIII IIIIIIIIIIII II
2、IIIIIIIIIHormone Therapy Response Rate (%) in Different Receptor StatusSurvival by Response Arimidex 1 mg0 020204040606080801001000 01 12 23 34 4CR or PRCR or PR Stable Stable 24 24 wkswks ProgressionProgressionYears from Years from RandomisationRandomisation% S u r v i v a l MA AGPrevention DCIS/ N
3、eoadj5 yearsMetastatic Disease 1st2nd3rdAdjuvantTAM TAMTAM TAMOV ABL三苯氧胺 （TAM) 最重要的乳癌内分泌治疗药物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%020406080100051015vs
4、RecurrencesBreast 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)vsYearsPercentTamoxifen Adjuvant Therapy for EBC 辅助内分泌治疗的决定因素是激素受体状况 ER阳性效果最好8Tamoxifen Adjuvant Therapy for EBC 合适的TAM服药时间为5
5、年9Tamoxifen Adjuvant Therapy for EBCER阳性无论年龄大小都可用TAM10Tamoxifen Adjuvant Therapy for EBC 降低对侧乳癌发生 增加子宫内膜癌的风险11Tamoxifen Adjuvant Therapy for EBCER阳性TAM和化疗合用比单用TAM更有效 CAF与TAM 序贯合用比同时效果更好 MA AGPrevention DCIS/ Neoadj5 yearsMetastatic Disease 1st2nd3rdAdjuvant1TAM TAMTAM TAMOV ABLTamoxifen Indications
6、in Breast Cancer三苯氧胺 乳癌内分泌治疗不可动摇的地位！？Survival Data Anastrozole / MAMedian time to death(months)2 year survival rate (%)P Anastrozole is = Exemestane is? Neoadjuvant Letrozole is Adjuvant ？ Anastrozole MilestonesActivated1996 Planned accrual9366 Accrual to dateClosed 1999 Ongoing AI Adjuvant Trials:
7、ATAC (Anastrozole)TrialistsTrialists Group TA. Group TA. Br J Cancer. 2001;85:317 2001;85:317.R A N D O M I Z ESurgeryTamoxifen 20 mg odAnastrozole 1 mg odTamoxifen 20 mg odAnastrozole 1 mg od5 yearsDFS/OSKaplanMeier Curves of KaplanMeier Curves of Disease-free Survival in ITT PopulationDisease-free
8、 Survival in ITT PopulationCurves truncated at 42 monthsHR95.2% CIp-valueAN vs TAM0.830.710.960.0129 Comb vs TAM1.020.881.180.7718TamoxifenAnastrozoleCombinationTime to event (months)Proportion event free (%)Time to event (months)Proportion event free (%)08085909510006121824303642KaplanMeier Curves
9、of Disease-free Survival in Receptor-positive PopulationCurves truncated at 42 monthsHR95.2% CIp-valueAN vs TAM0.780.650.930.0054 Comb vs TAM1.020.871.210.7786Time to event (months)Proportion event free (%)TamoxifenAnastrozoleCombination08085909510006121824303642Predefined adverse events* Hot flushe
10、sA Arimidex T Tamoxifen C Combination 1060TC1229 1243A% patientsA vs TC vs TA vs C0.791.020.78OR100102030405060nEndometrial thickness (mm)Median endometrial thickness024681001224Endometrial thickness (mm)Arimidex Tamoxifen CombinationTime (months)A vs TC vs TA vs C0.230.460.500.020.110.51ORp valueAT
11、CA, Arimidex; C, combination; T, tamoxifen3136% patientsPredefined adverse events Endometrial cancerATAC Summary Anastrozole 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: O
12、verall population (OR=0.42)Conclusions Anastrozole is the first and only AI to show superior efficacy and improved tolerability compared with tamoxifen in the treatment of EBC Overall risk-benefit assessment supports anastrozole becoming the future adjuvant treatment of choice in postmenopausal wome
13、n Anastrozole also shows promise for the chemoprevention of breast cancerAnalysis of the Incidence of New (Contralateral) Breast PrimariesTime to first contralateral new primary (months) 0612182430364209899100Proportion without CL BCa (%)AnastrozoleTamoxifenCombinationOR95% CIp-valueAN vs TAM0.420.2
14、20.790.0068 Comb vs TAM0.840.511.40 0.5132Arimidex (Anastrozole) in Breast cancer prevention:Design of IBIS II and data from ATACWhy use an Aromatase Inhibitor? At least as effective as tamoxifen in ABC ATAC trial provides early warning on side effects ATAC trial provides efficacy data in early brea
15、st cancer at all endpoints; striking reduction in contralateral breast cancer events Very low side-effect profile ATAC: incidence of new (contralateral) breast primaries in ITT population9 invasive 05101520253035Tamoxifen (n=3116)Arimidex (n=3125)Combination (n=3125)5 DCIS3 DCIS23 invasive5 DCIS30 i
16、nvasiveNo. casesArimidex vs tamoxifen OR 0.42; 95% CI 0.22, 0.79; p=0.007 Combination vs tamoxifen OR 0.84; 95% CI 0.51, 1.40; p=0.51Women-years of follow-up per arm 3100 x 2.8 = 8600 Rate of contralateral tumours in women not treated with tamoxifen (women-years)Expected contralateral tumoursObserved on tamoxifen46% reductionObserved on Arimidex
