江泽飞教授：乳腺癌骨转移进展

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master text styles,Second level,Third level,Fourth Level,Click to edit Master title style,*,Mastertitelformat bearbeiten,Mastertextformat bearbeiten,Zweite Ebene,Dritte Ebene,Vierte Ebene,Fnfte Ebene,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,Mastertitelformat bearbeiten,Mastertextformat bearbeiten,Zweite Ebene,Dritte Ebene,Vierte Ebene,Fnfte Ebene,*,*,Mastertitelformat bearbeiten,Mastertextformat bearbeiten,Zweite Ebene,Dritte Ebene,Vierte Ebene,Fnfte Ebene,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Mastertitelformat bearbeiten,Mastertextformat bearbeiten,Zweite Ebene,Dritte Ebene,Vierte Ebene,Fnfte Ebene,*,*,乳腺癌骨转移/骨健康治疗新进展,乳腺癌骨转移,概述,乳腺癌骨转移发生率为,65%,75%,。,乳腺癌远处转移首发症状为骨转移占,27%,50%,骨痛、骨损伤、骨相关事件（,SREs,）及生活质量降低是乳腺癌骨转移的常见并发症,骨相关事件包括（,SREs),1-3,：,病理性骨折（椎体骨折、非椎体骨折）,脊髓压迫,骨放疗,(,因骨痛或防治病理性骨折或脊髓压迫,),骨手术,高钙血症,1.Coleman RE.Cancer Treat Rev.2001 Jun;27(3):165-76.2.John R.Johnson,Grant Williams,et al.J Clin Oncol 21:1404-1411.3.Kinnane N.Eur J Oncol Nurs.2007;11 Suppl 2:S28-31.Epub 2007 Sep 4.,骨转移的诊断方法,骨转移初筛诊断方法：骨放射性核素扫描（,ECT,）,推荐用于出现骨疼痛、骨折、,AKP,升高、或高钙血症等可疑骨转移的常规初筛诊断检查,乳腺癌分期,T3N1M0,患者常规检查,复发转移乳腺癌患者的常规检查,骨转移的影像学确诊检查方法：骨,X,线,/CT/MRI,骨活检：必要时可获病理诊断,PET-CT,和骨代谢生化指标目前不能成为常规诊断方法,乳腺癌骨转移的临床表现,多发溶骨性病变常见,乳癌骨转移特点：骨转移疼痛严重影响,QOL,，但骨转移本身一般不直接威胁生命；有效治疗手段多，未合并内脏转移的生存期相对较长,治疗目标,预防和治疗骨相关事件（,SREs,）,缓解疼痛,恢复功能，改善生活质量,控制肿瘤进展，延长生存期,治疗方法,化疗、内分泌治疗、分子靶向治疗等,双膦酸盐治疗,手术治疗,放射治疗,镇痛和其他支持治疗,双膦酸盐临床应用及研究,:,时间表,高钙血症,骨痛,预防,SRE,无疾病进展,?,总生存,?,CTIBL,肿瘤骨转移,辅助治疗,DFS/OS?,SRE:,骨相关事件,;CTIBL:,肿瘤治疗引起的骨丢失,;DFS:,无病生存率,;OS:,总生存,双膦酸盐临床应用及研究,:,时间表,高钙血症,骨痛,预防,SRE,无疾病进展,?,总生存,?,CTIBL,肿瘤骨转移,辅助治疗,DFS/OS?,SRE:,骨相关事件,;CTIBL:,肿瘤治疗引起的骨丢失,;DFS:,无病生存率,;OS:,总生存,骨转移恶性循环,肿瘤细胞,破骨细胞,1,2,2,3,1.,肿瘤细胞释放细胞因子激活破骨细胞活性,3.,骨病灶释放生长因子促进肿瘤细胞生长,2.,破骨细胞溶解骨质,双膦酸盐,缩写,:BMP,骨形态发生蛋白,;IGF-1,i,胰岛素样生长因子,1;TGF-,转化生长因子,-,.,Data from Coleman R.,Clin Breast Cancer.,2007;7(suppl 1):S29-S35;Kingsley LA,et al.,Mol Cancer Ther.,2007;6(10):2609-2617;Winter MC,et al.,Cancer Treat Rev.,2008;34(5):453-475.,双膦酸盐可以用于治疗乳腺癌的骨转移,SREs,相关并发症,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.,尽早使用双膦酸盐,预防,SREs,疗效更好,Costa L,et al.Presented at:31st Annual European Society for Medical,Oncology,2006.Abstract 178P.,Patients with an SRE,%,51%,51%,基线有骨痛症状,发生,SRE,患者,%,22,37%,基线无骨痛症状,0,5,10,15,20,25,30,35,40,唑来膦酸,帕米膦酸,22%,P=0.097,风险降低,研究扩展期,(13 25,月,),相对风险,有利于唑来膦酸,有利于帕米膦酸,0,0.2,0.4,0.6,0.8,1,1.2,1.4,1.6,1.8,2,.026,P,值,0.591,41%,.025,0.799,20%,总体,25,个月随访,长期治疗双膦酸盐使乳腺癌患者持续获益,在第二年治疗期间，患者发生,SRE,风险仍然低于帕米膦酸*,*,Andersen-Gill,多事件分析,Zheng M,et al.Presented at:Primary Therapy of Early Breast Cancer 9th International Conference;January 26-29,2005;Abstract 104.,应用,双,膦酸盐过程中,再次,发生,SREs,临床实践中不应停用,双膦酸盐,，应该继续用药,以预防下次,SREs,的发生,。,风险降低,相对风险,有利于唑来膦酸,有利于帕米膦酸,0,0.2,0.4,0.6,0.8,1,1.2,1.4,1.6,1.8,2,P,值,所有,SRE,.015,0.711,29%,.045,0.690,31%,除了首次,SRE,唑来膦酸比帕米膦酸减少,1/3,的第二次,SRE,风险*,*,Andersen-Gill,多事件分析,Adapted from Zheng M,et al.Presented at:Primary Therapy of Early Breast Cancer 9th International Conference;January 26-29,2005;Abstract 104.,中国乳腺癌专家共识对于双膦酸盐,用药时间,的推荐,双膦酸盐用于乳腺癌患者治疗和预防,SREs,的临床研究中，各临床试验中位用药时间为,618,个月，已有用药,2,年以上的安全性数据，因此临床实践中推荐用药时间,可达,2,年,并应该根据患者的获益情况主张合理的长期用药，有时可能成为晚期骨转移患者唯一保留的全身用药,江泽飞等,乳腺癌骨转移和骨相关疾病临床诊疗专家共识,(,20,10,版,),双膦酸盐临床应用及研究,:,时间表,高钙血症,骨痛,预防,SRE,无疾病进展,?,总生存,?,CTIBL,肿瘤骨转移,辅助治疗,DFS/OS?,SRE:,骨相关事件,;CTIBL:,肿瘤治疗引起的骨丢失,;DFS:,无病生存率,;OS:,总生存,肿瘤治疗加速骨质丢失,正常男性,1,绝经早期女性,1,绝经晚期女性,1,接受,AI,治疗的绝经后女性,2,雄激素去势治疗（,ADT,）,4,AI,治疗,+GnRH,激动剂,5,化疗引起的卵巢功能衰竭,6,骨髓移植,3,1.,Osteoporos Int.1997;7(1):1-6.;2.Eastell R,et al.J Bone Miner Res.2006;21(8):1215-1223;3.Lee WY et al.J Clin Endocrinol Metab.2002;87(1):329-325;4.Maillefert JF,et al.J Urol.1999;161(4):1219;5.Gnant M,et al.Breast Cancer Res Treat.2002;76(suppl 1):S31.Abstract 12;6.Shapiro CL,et al.J Clin Oncol.2001;19(14):3306-3311.,双膦酸盐预防内分泌治疗引起的骨丢失,a,患者接受黄体生成素释放激素激动剂,+,他莫西芬或者阿那曲唑,.,缩写,:ANA,阿那曲唑,;IBAN,伊班膦酸,;LET,来曲唑,;RIS,利塞膦酸,.,1.Gnant M,et al.,Lancet Oncol.,2008;9(9):840-849;2.Brufsky AM,et al.,Clin Breast Cancer,.2009;9(2):77-85;3.Eidtmann H,et al.,A