唑来膦酸在乳腺癌中的临床研究进展课件.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,文档仅供参考，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。,唑来膦酸（择泰）的研发历程,治疗晚期乳腺癌骨转移,预防早期乳腺癌,AI,治疗引起的骨丢失,预防早期乳腺癌术后复发,唑来膦酸（择泰）的研发历程,治疗晚期乳腺癌骨转移,预防早期乳腺癌,AI,治疗引起的骨丢失,预防早期乳腺癌术后复发,骨相关事件（,SREs,）包括：,放疗,缓解重度疼痛,治疗和预防病理性骨折或脊髓压迫,病理性骨折,锥体骨折,其他骨折,脊髓压迫,骨骼手术,恶性肿瘤所致高钙血症（,HCM),FDA,已接受骨相关事件（,SREs）,作为评价双膦酸盐临床疗效的主要研究终点,Johnson JR,et al.J Clin Oncol.2003;21:1404-1411,Williams G et al.J Biopharm Stat.2004 Feb;14(1):5-21,骨转移导致骨相关事件（SREs）的发生,双膦酸盐治疗目标-SRE,SRE,发生导致疾病进展、生活质量降低、生存期缩短、并引起医疗费用增加,1-3,预防或延缓,SRE,发生，减少,SRE,发生次数是减缓疾病进展和维持患者功能独立性的重要环节,双膦酸盐治疗综合而且全面覆盖以上目标,4,Coleman RE.,Cancer,.1997;80(suppl):1588-1594.,Delea T et al.,Oncology,.2004;67:390-396.,Jacobson AF et al.,Cancer,.2001;91:17-24.,4.Coleman RE.,Oncologist,.2000;5:463-4670.,乳腺癌骨转移，择泰对照帕米膦酸010,研究设计,0,25,月,最终分析,双盲、双模拟研究，旨在证实：与帕米膦酸二钠,相比，唑来膦酸具有非劣效性,唑来膦酸,8/4mg，1,次/,34,周,随机化分组,唑来膦酸,4 mg，1,次/,34,周,n=564,n=526,帕米膦酸二钠,90 mg，1,次/,34,周,三组均每日口服维生素,D 400 IU,及钙,500 mg,n=558,1,130,例,IV,期乳腺癌患者,518例多发性骨髓瘤患者,13,月,核心分析,Rosen LS et al.Cancer J.2003;98:1735-44,415,370,349,366,乳腺癌化疗,乳腺癌激素治疗,延缓30%，,P0.05,P=NS,唑来膦酸,4,mg,帕米膦酸二钠90,mg,唑来膦酸明显延缓乳腺癌患者骨相关事件(,SREs),的发生,Rosen LS et al.Cancer J.2003;98:1735-44,.,至首次骨相关事件(,SREs),天数,唑来膦酸显著降低乳腺癌患者骨相关事件(,SREs),发生危险达,20%,多事件分析,危险比,(95%可信区间),P,值,0.030,0.025,所有患者,(,n=1,648),乳腺癌患者,(,n=1,130),0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2,有利于唑来膦酸,有利于,帕米膦酸二钠,0.799,0.841,唑来膦酸显著降低骨相关事件(,SREs),发生危险达20%，优于帕米膦酸二钠,危险降低,20%,16%,Rosen LS et al.Cancer J.2003;981735-44,010研究,疗效总结,唑来膦酸有效降低乳腺癌患者的骨相关事件(,SREs),危险，疗效优于帕米膦酸二钠,唑来膦酸,4mg,463760.910.799,帕米膦酸二钠,90,mg493661.57,P,值.189.186.102,.025,发生,SREs,的患者比例,%,至,SREs,的中位时间（天）,*,骨相关事件年发病率*,多事件分析危险比*,*恶性肿瘤所致的高钙血症(,HCM),被包括在骨相关事件(,SREs),内。,Rosen LS et al.Cancer J.2003;98:1735-44,乳腺癌骨转移，择泰对照安慰剂,1501,研究设计（日本）,多中心、随机、双盲安慰剂对照研究,随机分组,唑来膦酸 4,mg，,静脉输注15,min，,每4周，共12个月,n=114,安慰剂，静脉输注15,min，,每4周，共12个月,n=114,（,n=228）,Kohno N,et al.,J Clin Oncol,.2005;23:3314-3321.,唑来膦酸显著降低发生一次,SRE,的患者比例,P,=.003,相对值,39%,Kohno N,et al.J Clin Oncol.2005;23:3314-3321.,唑来膦酸显著降低骨并发症风险达,41%,*Andersen-Gill,多事件分析,#,采用严格变量，根据既往是否发生过骨折进行分层的回归系数的,Wald,检验,降低风险,相关风险,有利于唑来膦酸,有利于安慰剂,0,0.2,0.4,0.6,0.8,1,1.2,1.4,1.6,1.8,2,.001,P,值,.59,41%,Kohno N,et al.J Clin Oncol.2005;23:3314-3321.,唑来膦酸显著降低平均复合,BPI,疼痛评分,较基线变化的平均值,2,4,8,12,16,20,24,28,32,36,40,44,48,52,自研究开始的时间，周,*,*,*,*,*,*,*,*,*,*,*,0,*,*,减轻骨痛,增加骨痛,*,P,.05.,Kohno N,et al.J Clin Oncol.2005;23:3314-3321.,安慰剂对照试验中双膦酸盐治疗乳腺癌的疗效,氯屈膦酸（口服）,1,600 mg,(Kristensen)31%,(Paterson)17%,(Tubiana-Hulin)8%,P,值,风险,降低,0,0.2,0.4,0.6,0.8,1,1.2,1.4,1.6,1.8,2,唑来膦酸,4 mg 41%.001,(Kohno 2005),.59,帕米膦酸,90 mg 23%.001,(Aredia study 18&19),.,77,伊班膦酸,6 mg 18%.004,(Body 2003),.,82,伊班膦酸,50 mg 14%.08,(Body 2004),.,86,.,69,.,83,.,92,.03,总,(95%CI)21%.001,Pavlakis N,et al.,Cochrane Database Syst Rev,.2005;4:1-38.,ASCO,乳腺癌骨转移治疗指南,推荐,X,线,/CT/MRI,等影像学检查有骨破坏时开始使用静脉双膦酸盐,推荐每,3-4,周使用静脉唑来膦酸,(4 mg via 15-minute infusion),或帕米膦酸,(90 mg via 2-hour infusion),未推荐口服双膦酸盐,双膦酸盐应持续使用直至患者不能耐受或一般状况显著下降,Hillner B,et al.,J Clin Oncol,.2003;21:4042-4057.,小 结,治疗和预防,SRE,，维持患者功能独立性和生活质量是肿瘤骨转移治疗的目标,010,和,1501,试验奠定了择泰在乳腺癌骨转移治疗中的地位,指南推荐乳腺癌骨转移优先选择唑来膦酸，并建议长期使用，可以最大程度减少,SRE,发生,唑来膦酸（择泰）的研发历程,治疗晚期乳腺癌骨转移,预防早期乳腺癌,AI,治疗,引起的骨丢失,预防早期乳腺癌术后复发,Years,Lumbar spine BMD,ATAC,1,Anastrozole vs tamoxifen upfront,IES,2,Exemestane vs tamoxifen following switch after 2-3 years tamoxifen,MA-17,3,Letrozole vs placebo following switch after 5 years on tamoxifen,TEAM,4,Exemestane vs tamoxifen for 2-3 years (before switching from TAM to EXE vs.EXE for 5 years),芳香化酶抑制剂治疗导致快速骨丢失,1.Howell A,et al.,Lancet,2005;365:60-62;2.Coleman RE,et al.,Lancet Oncol.,2007;8:119-127;3.Goss PE,et al.,J Natl Cancer inst,.2005;97:1262-1271;,4.Hadji P,et al.Presented at 31,st,Annual San Antonio Breast Cancer Symposium,San Antonio,TX,USA;December 10-14,2008;Abstract 1143.,F/U,follow-up;NS,not significant;ATAC,Arimidex tamoxifen alone or in combination;IES,intergroup exemestane study;BIG 1-98,breast international group 1-98 collaborative group;TEAM,Tamoxifen exemestane adjuvant multinational.,1.Adapted from Hadji P,et al.,US Oncological Disease,.2007;1:18-21;2.Howell A,et al.,Lancet,.2005;365(9453):60-62;3.Coleman RE,et al.,Lancet Oncol,.2007;8:119-127;4.Thurlimann B,et al.,N Engl J Med,.2005;353(26):2747-2757;5.Goss PE,et al.,J Natl Cancer Inst,.2005;97(17):1262-1271;6.Jones SE,et al.Presented at 31,st,Annual San Antonio Breast Cancer Symposium,San Antonio,TX,USA;December 10-14,2008;Abstract 15.,Fractures,%,11,7.7,5.7,4.0,5.3,4.6,7.0,5.0,P,.0001,P,.001,0,2,4,6,8,10,12,P=,.003,P,=.25,Tamoxifen,Letrozole,Anastrozole,Placebo,Exemestane,ATAC,2,6,186,68 months,IES,3,4,724,58 months,BIG 1-98,4,8,010,26 months,MA.17,5,5,187,30 months,所有的芳香化酶抑制剂均增加骨折风险,1,N=,Median F/U=,2.3,2.7,P,=NS,TEAM,6,9,670,33 months,维护骨健康可以减少后续骨折和死亡风险,AIBL,比绝经后骨丢失更快速,1,2,双膦酸盐等有效的骨代谢治疗，可以预防潜在的骨丢失,双膦酸盐治疗还可能进一步减少骨转移风险,3,4,5,AIBL,aromatase inhibitor-associated bone loss.1.,Osteoporosis Int,.1997;7(1):1-6;2.Eastell R,et al.,J Bone Miner Res,.2006;21(8):1215-1223;3.Daubine F,et al.,J,Natl Cancer Inst,.2007;99(4):322-330;4.Mystakidou K,et al.,Med Oncol.,2005;22(2):195-201;5.Diel I,et al.,New Eng J Med,.1998;339(6):357-363.,双膦酸盐治疗,AIBL,机理,ABCSG-12:,绝经前女性接受辅助内分泌治疗,+,唑来膦酸,1999 to 2006,1,800,例绝经前女性乳腺癌患者,I&II,期,LNM,10,个,ER,+,和,/,或,PgR,+,治疗时间,:3,年,允许接受术前化疗,骨研究（,n=404,）于,6/03,结束,他莫昔芬,他莫昔芬,+,唑来膦酸,(4 mg)*q 6 mo,阿那曲唑,+,唑来膦酸,(4 mg)*q 6 mo,阿那曲唑,3 years,final BMD,随,机,*8 mg reduced to 4 mg.,ABCSG-12=Austrian,Breast and Colorectal Cancer Study Group Trial 12.,Gnant MF,et al.,J Clin Oncol,.2007;25:820-828,.,手术,(+,放疗,),戈舍瑞林,3.6 mg/28 days,基线,BMD,6-month BMD,60,个月随访数据：腰椎,BMD%,变化结束唑来膦酸治疗后,BMD,继续改善,Gnant MF.Presented at,SABCS 2007,Abstract#26,Z-FAST,1,ZO-FAST,2,E-ZO-FAST,3,试验设计,0,5 yearsFinal analysis,ZOL 4 mg q 6 mo+LET 2.5 mg die,(DELAYED),*,ZOL 4 mg q 6 mo+LET 2.5 mg die,(UP FRONT),R,A,N,DO,M,I,Z,E,D,3 years,1 year,PMW=Postmenopausal women;CT=Chemotherapy.*Initiation of zoledronic acid determined by postbaseline BMD T-score 1 or between 1 and 2),P,values correspond to intergroup comparisons.DMD,bone mineral density;ZOL,zoledronic acid.,a,Initiated only after T-score decreases below 2 or clinical fracture unrelated to trauma.,1.Brufsky A,et al.Presented at:6th Annual EBCC;April 15-19,2008.Abstract 494;2.Brufsky A,et al.Presented at:30th Annual SABCS;December 13-16,2007.Abstract 27.,Upfront ZOL,Delayed ZOL,Z-FAST,36,个月：初始唑来膦酸治疗明显改善腰椎和膝关节,BMD,(N=602),Multicenter,open-label,randomized phase III study of upfront vs.delayed,a,zoledronic acid(4 mg q 6 months)in postmenopausal women receiving letrozole(N=602)for 5 years,Month 24,1,腰椎,膝关节,Mean(SEM)change BMD,%,P,.0001,P,.0001,P,.0001,P,.0001,Month 12,1,Month 24,1,Month 12,1,4%,3%,2%,1%,0%,1%,2%,3%,4%,Month 36,2,Month 36,2,P,.001,P,.001,n=251,n=256,n=204,n=199,n=189,n=188,n=251,n=256,n=206,n=197,n=189,n=187,4.4%,5.9%,6.7%,3.3%,4.7%,5.2%,ZO-FAST,36,个月：,初始唑来膦酸治疗明显改善腰椎和膝关节,BMD,(N=1,064),3,P,65,岁,年龄,60,-,64,岁,骨折家族史,体重,70,公斤,既往非外伤性骨折史,其他风险因素,任何年龄接受芳香化酶抑制剂患者,绝经前患者因为治疗引起闭经,建议每年一次的,BMD,监测,Hillner BE,et al.,J Clin Oncol.,2003;21(21):4042-4057.,BMD T-score,1,BMD T-score between,1 and 2.5,BMD T-score,2.5,基础治疗：饮食和生活方式改变,提供钙和维生素,D,个体化地反复评价,骨折发生风险,根据个体情况,考虑药物治疗,药物治疗,-,Alendronate,-Risendronate-Zoledronate,-Raloxifene*,*Not to be used with tamoxifen or with Al.,Hillner BE,et al.,J Clin Oncol.,2003;21:4042-4057.,ASCO,2003,指南,:,根据,BMD,变化治疗,T-score 2.0,任意,2,项以下风险因素,:,T-score 65 years,低体重指数,(6 months,吸烟（现在或既往）,T-score,2.0,没有其他危险因素,每,1-2,年监测风险状态和,BMD*,唑来膦酸,(4 mg/6 months),补充钙和维生素,D,每,2,年监测,BMD,补充钙和维生素,D,*,5%drop in BMD should trigger zoledronic acid treatment(4 mg/6 months).Use lowest T-score from 3 sites.,Hadji P,et al.Presented at:SABCS 2007.Abstract 504.,专家指南更新：结合,BMD,和,其他风险因素,治疗,目前已经有了口服双膦酸盐的试验结果,4,个临床试验的数据提示唑来膦酸预防,AIBL,小 结,AI,治疗减少,BMD,并增加骨折风险,多项大型临床试验证实唑来膦酸治疗获益超过了单纯的骨保护作用,内分泌治疗联合唑来膦酸,(4 mg q 6 mo),保持,BMD,，而且改善疾病进展,(DFS),1,2,3,临床指南的权威推荐,建议高危患者积极筛查,BMD,双膦酸盐治疗不仅参考,BMD,，也应结合其他风险因素,AI,aromatase inhibitor;BMD,bone mineral density;BP,bisphosphonate;AIBL,aromatase inhibitor-associated bone loss;DFS,disease-free survival.,1.Gnant M,et al.,J Clin Oncol.,2008(suppl).Abstract LBA4;2.Frassoldati A,et al.Presented at:33rd Annual ESMO;September 12-162008.Abstract 185PD;3.Eidtmann H,et al.Presented at:31st Annual SABCS;December 10-14,2008.Abstract 44.,唑来膦酸（择泰）的研发历程,治疗晚期乳腺癌骨转移,预防早期乳腺癌,AI,治疗引起的骨丢失,预防早期乳腺癌术后复发,减少细胞因子的产生,(,如,IL-6),1,直接的抗肿瘤活性,(,细胞抑制和细胞溶解,),2-5,抑制肿瘤细胞扩散、侵犯及与骨基质的粘附,6,7,抑制血管生成,8,Reference 1-8,唑来膦酸比传统双膦酸盐更加独特的作用机理,1.Derenne S,J Bone Miner Res.1999;14:2048-2056.2.Aparicio A,.1998;12:220-229.,3.FromiguO,J Bone Miner Res.2000;15:2211-2221.4.Senaratne SG,Br JCancer.2000;82:1459-1468.,5.Jagdev SP,Bone.2000;26:S30.Abstract B11.6.Boissier S,Cancer Res.2000;60:2949-2954.,7.Marion G,Bone.1998;23:S279.Abstract8.Wood J,Pharm Exp Ther.In press.,绝经前乳腺癌：,ABCSG-12,试验设计,收集于,1999-2006,1,803,例绝经前的乳腺癌患者,内分泌疗法有效,(,雌激素受体和,/,或孕激素受体阳性,),I&II,期,10,处淋巴结转移,除新辅助化疗外未接受其他化疗,治疗时程,:3,年,31,随机分组,1:1:1:1,手术,(+,放疗,),三苯氧胺,20 mg/,天,戈舍瑞林,3.6 mg 28,天一次,阿那曲唑,1 mg/,天,+,唑来膦酸,4 mg,6,个月一次,阿那曲唑,1 mg/,天,三苯氧胺,20 mg/,天,+,唑来膦酸,4 mg 6,个月一次,Gnant M,et al.Presented at:ASCO 2008.,Chicago,IL.Abstract LBA4,试验情况,1999,年至,2006,年间共征募了,1,803,位患者,中位随访时间,:48,个月,2008,年,3,月,:137,例,发生,事件,42,例死亡,30,例局部复发病例,70,例远处复发病例,包括,40,例骨转移事件,16,例对侧乳腺癌,19,例新生非乳腺肿瘤,总计,:4,年无病生存率,=94%;4,年总生存率,=98.2%,32,Gnant M,et al.Presented at:ASCO 2008.,Chicago,IL.Abstract LBA4,与单独使用内分泌治疗相比唑来膦酸显著提高无病生存率,36%,(DFS)100,90,80,70,60,50,40,30,20,10,0,0,12,24,36,48,60,72,84,随机分组后时间,月,无病生存率,%,发生数,风险比,(95%CI)/#,存在风险数,vs,不使用,ZOL,P,值,ZOL54/8990.643(0.46,0.91).011,No ZOL83/904,平均随访时间,=60,月,.DFS=,无病生存率,;CI=,置信区间,;ZOL=,唑来膦酸,.Gnant M,et al.Presented at:ASCO 2008.Chicago,IL.Abstract LBA4.,与单独使用内分泌治疗相比,唑来膦酸显著提高无复发生存率,35%,(RFS),100,90,80,70,60,50,40,30,20,10,0,0,12,24,36,48,60,72,84,随机分组后时间,月,无复发生存率,%,发生数,风险比,(95%CI)/#,存在危险数,vs,不使用,ZOL,P,值,ZOL54/8990.653(0.46,0.92).014,No ZOL82/904,平均随访时间,=60,月,.RFS=,无复发生存率,;CI=,可,信区间,;ZOL=,唑来膦酸,.,Gnant M,et al.Presented at:ASCO 2008.Chicago,IL.Abstract LBA4,.,经唑来膦酸治疗的病人中表现出非显著性趋势总生存率os),增高,100,90,80,70,60,50,40,30,20,10,0,0,12,24,36,48,60,72,84,随机分组后时间,月,总生存率,%,发生数,风险比,(95%CI)/#,存在危险数,vs,不使用唑来膦酸,P,值,ZOL16/8990.595(0.32,1.11).101,No ZOL26/904,平均随访时间,=60,月,.OS=,总生存率,;CI=,可,信区间,;ZOL=,唑来膦酸,.,Gnant M,et al.Presented at:ASCO 2008.Chicago,IL.Abstract LBA4.,主要无病存活事件,(,意向治疗人群,ITT),主要事件,/,病人,n,(n=904),(n=899),不使用,ZOL vs ZOL,DFS=,无病生存率,;ITT=,意向治疗,;ZOL=,唑来膦酸,.,Gnant M,et al.Presented at:ASCO 2008.Chicago,IL.Abstract LBA4.,需要治疗病人数,(NNT),估算,为了使,1,位患者获得无病生存（,DFS,）的临床收益需要治疗的病人数,NNT=1/,绝对风险减低,唑来膦酸具有与其他化疗药物相似的改善,DFS,功效,(ie,紫杉烷类,),*,Bria E,et al.,Cancer,.2006;106:2337-2344.,小结：唑来膦酸治疗和非唑来膦酸治疗,与单纯内分泌治疗相比，唑来膦酸显著延长,DFS,和,RFS,36%DFS,事件风险,(HR=0.64;P=.01),35%RFS,事件风险,(HR=0.65;,P,=.015),无论在骨内还是在骨外，唑来膦酸均显示了获益：,降低对侧乳腺癌复发,降低局部复发,降低非骨转移,仍需要开展进一步的临床研究探讨最佳剂量、给药方法和给药间隔。,应考虑将唑来膦酸列入辅助治疗以改善绝经前乳腺癌妇女的治疗,ZOL=,唑来膦酸,;DFS=,无病生存率,;RFS=,无复发生存率,;OS=,总体存活率,;HR,风险比,.,Gnant M,et al.Presented at:ASCO 2008.,Chicago,IL.Abstract LBA4,绝经后乳腺癌：,ZO-FAST 36,个月随访,来自亚太、中南美、埃及和欧洲,128,个研究中心的,1065,患者入选,入选标准：,ER+/PgR+,早期乳腺癌；,绝经后；,骨密度,T,值,2,。,患者分层：,辅助,CT,T,值,确诊的和近期绝经,来曲唑,2.5 mg/,天,加用唑来膦酸，如果,:BMD T,值,2,或,非创伤性骨折或,36,个月随访中确认的无症状的骨折,5,年,唑来膦酸,4 mg,，,IV,，,1,次,/6,个月,来曲唑,2.5 mg/,天,早期使用,延迟使用,1065,例,患,者,随,机,分,组,主要研究终点：,12,个月时腰椎（,L2L4,）,BMD,变化百分比。,次要研究终点：,3,年骨折发生率；,至疾病复发时间；总生存时间,；两治疗组的总体安全性。,Adapted from Eidtmann H,et al.Presented at:31st Annual San Antonio Breast Cancer Symposium;December 10-14,2008;San Antonio,TX.Abstract 44.,时间（月）,无病生存率（,DFS,），,%,60,0,40,20,80,100,10,20,15,5,35,30,25,0,早期治疗组,延迟治疗组,择泰早期治疗显著降低无病生存率，风险比,0.588P,=0.0314,早期治疗组显著降低无病生存率,DFS,Adapted from Eidtmann H,et al.Presented at:31st Annual San Antonio Breast Cancer Symposium;December 10-14,2008;San Antonio,TX.Abstract 44.,疾病复发：局部复发，远处转移或死亡,早期治疗,N=532,患者数（,%,）,延迟治疗,N=532,患者数（,%,）,第,12,个月,15(2.8),17(3.2),第,24,个月,21(3.9),32(6.0),第,36,个月,26(4.9),43(8.1)Adapted from Eidtmann H,et al.Presented at:31st Annual San Antonio Breast Cancer Symposium;December 10-14,2008;San Antonio,TX.Abstract 44.,复发部位,早期治疗组,N=532,n(%),延迟治疗组,N=532,n(%),局部复发,2(0.4),10(1.9),远处复发,*,骨,脑,淋巴结,肝,肺,皮肤,其他,20(3.8),9(1.7),4(0.8),5(0.9),5(0.9),4(0.8),0,7(1.3),30(5.6),17(3.2),3(0.6),30.6),3(0.6),6(1.1),7(1.3),12(2.3),*患者可能有多个复发部位,Adapted from Eidtmann H,et al.Presented at:31st Annual San Antonio Breast Cancer Symposium;December 10-14,2008;San Antonio,TX.Abstract 44.,死亡率（治疗期间任何原因引起）,死亡率，,%,Adapted from Eidtmann H,et al.Presented at:31st Annual San Antonio Breast Cancer SymposiumDecember 10-14,2008;San Antonio,TX.Abstract 44.,ZO-FAST 36,个月结论,使用,AI,辅助治疗的早期乳腺癌患者早期使用择泰（,4mg IV 1,次,/6,个月）能够预防骨质丢失；,早期使用择泰和延迟使用择泰在骨折发生率方面无显著差异；,早期使用择泰显著提高无病生存率；,药物安全性结果与以往一致：无药物相关肾损害,;,下颌骨坏死,，早期治疗组,1,例（,0.2%,），接受,6,次唑来膦酸治疗，延迟治疗组：无,这些结果进一步证明择泰治疗早期乳腺癌具有抗肿瘤活性并延长无病生存期。,总 结,唑来膦酸已经成为乳腺癌骨转移的标准治疗之一，有效减少,SRE,发生，并维护患者功能独立性和生活质量,唑来磷酸可以预防早期乳腺癌接受,AI,治疗引起的骨质丢失，减少骨折发生和骨折引起的死亡风险,临床研究证实唑来膦酸具有抗肿瘤作用，联合内分泌治疗和化疗，显著减少乳腺癌术后复发风险，并可能延长总生存率,唑来膦酸的抗肿瘤特性仍待其他正在进行中的临床试验进一步确证,谢 谢！,