目的 探索乳腺癌骨转移骨相关事件（skeletal-related event,SRE）的危险因素,为早期预防和减少SRE提供临床理论依据。方法 检索2000年1月1日至2017年10月31日,Pubmed、Web of Science、中国知网（CNKI）、维普数据库（VIP）及万方数据库中对乳腺癌骨转移SRE危险因素进行分析的中英文文献,提取相关信息和结论。对2004年4月至2016年12月间复旦大学附属中山医院和上海市黄浦区中心医院收治的104例乳腺癌骨转移病人随访并记录SRE的发生,分析SRE危险因素。结果 系统复习的文献最终纳入6篇。SRE危险因素包括病人年龄、ER/PR/HER2、组织/核分级、临床分期、骨转移持续时间、骨转移部位数、手术方式等。对这些因素行单因素和（或)多因素分析。6篇文献结论略有差异,多数结论支持临床分期晚、骨转移持续时间长、骨转移部位数多为SRE危险因素。104例乳腺癌骨转移病人中位随访60个月,58例发生SRE。单因素和多因素分析的结果是,初诊远处转移（P=0.017）和多发骨转移灶（P=0.008）为SRE的独立危险因素。回顾分析的结果与系统复习结论较一致。结论 文献系统复习和104例回顾分析显示,临床分期越晚、骨转移持续时间长、骨转移部位数目越多可能是SRE危险因素,而年龄、乳腺癌分子分型、组织/核分级、手术方式等并非SRE危险因素。
Objective To explore the risk factors of skeletal-related event(SRE) in breast cancer patients with bone metastases in order to provide clinical base for early prevention of SRE. Methods A systematic literature search from PubMed, Web of Science, CNKI, VIP and Wanfang Data was conducted for the study on risk factors of SRE in breast cancer patients with bone metastases published in Chinese or English between January 1 2000 and October 31 2017. Then relevant information and conclusion were extracted. A total of 104 breast cancer patients with bone metastases from April 2004 to December 2016 in Zhongshan Hospital Fudan University and Shanghai Huangpu District Central Hospital were followed up for SRE. The risk factors of SRE were analyzed. Results Six literatures met the inclusion criteria and were included, which provided univariable and/or multivariable analysis of the risk factors of SRE including patient age, ER/PR/HER2, histological/nuclear grade, clinical stage of disease, duration of bone metastases, number of bone metastases sites and type of surgery. Most studies supported later clinical stage, longer duration of bone metastases and more sites of bone metastases were risk factors of SRE although the conclusions of 6 literatures were different slightly. During median follow-up of 60 months, 58 of 104 cases occurred SRE. Both primary distant metastasis (P=0.017) and multiple bone metastases sites (P=0.008) were independent risk factors of SRE by univariable and multivariable analysis. Similar results were gotten in retrospective study and systematic review. Conclusions It was shown by systematic review and retrospective analysis with 104 cases that later clinical stages, longer duration of bone metastases and more bone metastases sites were probably the risk factors of SRE. Nevertheless, age, molecular classification of breast cancer, histological/nuclear grade or surgery type etc. were not necessarily related to SRE.
[1] Siegel RL, Miller KD, Jemal A.Cancer statistics, 2016[J]. CA Cancer J Clin,2016,66(1):7-30.
[2] Desantis CE, Fedewa SA, Goding Sauer A, et al.Breast cancer statistics, 2015: Convergence of incidence rates between black and white women[J]. CA Cancer J Clin,2016,66(1):31-42.
[3] Fan L, Strasser-Weippl K, Li JJ, et al.Breast cancer in China[J]. Lancet Oncol,2014,15(7):e279-e289.
[4] Shi J, Liang D, Jin J, et al.Female breast cancer burden was increasing during the 40 years in Hebei Province, China: a population-based study[J]. Arch Gynecol Obstet,2016,294(5):1-9.
[5] Mundy GR.Metastasis to bone: causes, consequences and therapeutic opportunities[J]. Nat Rev Cancer,2002,2(8):584-593.
[6] Harries M, Taylor A, Holmberg L, et al.Incidence of bone metastases and survival after a diagnosis of bone metastases in breast cancer patients[J]. Cancer Epidemiol,2014,38(4):427-434.
[7] Svendsen ML, Gammelager H, Sværke C, et al.Hospital visits among women with skeletal-related events se-condary to breast cancer and bone metastases: a nationwide population-based cohort study in Denmark[J]. Clin Epidemiol,2013,5:97-103.
[8] Stewart LA, Clarke M, Rovers M, et al.Preferred repor-ting items for a systematic review and Meta-analysis of individual participant data: The PRISMA-IPD statement[J]. JAMA,2015,313(16):1657-1665.
[9] Lo KL, Mertz D, Loeb M.Newcastle-Ottawa Scale: comparing reviewers' to authors' assessments[J]. BMC Med Res Methodol,2014,14(1):45.
[10] Dibekoglu C, Turanli S, Karaman N, et al.Bone fracture in breast cancer patients with isolated bone metastasis[J]. Chirurgia,2015,110(1):43-48.
[11] Yamashiro H, Takada M, Nakatani E, et al.Prevalence and risk factors of bone metastasis and skeletal related events in patients with primary breast cancer in Japan[J].Int J Clin Oncol,2014,19(5):852-862.
[12] Kuchuk I, Hutton B, Moretto P, et al.Incidence, consequences and treatment of bone metastases in breast cancer patients-Experience from a single cancer centre[J]. J Bone Oncol,2013,2(4):137-144.
[13] 丁晓燕, 樊英, 马飞, 等. 绝经后乳腺癌骨转移病人骨相关事件及预后分析[J]. 肿瘤防治研究,2012,39(6):627-631.
[14] Trinkaus M, Simmons C, Myers J, et al.Skeletal-related events (SRE) in breast cancer patients with bone metastases treated in the nontrial setting[J]. Support Care Cancer,2010,18(2):197-203.
[15] Domchek SM, Younger J, Finkelstein DM, et al.Predictors of skeletal complications in patients with metastatic breast carcinoma[J]. Cancer,2000,89(2):363-368.
[16] Carter JA, Ji X, Botteman MF.Clinical, economic and humanistic burdens of skeletal-related events associated with bone metastases[J]. Expert Rev Pharmacoecon Outcomes Res,2013,13(4):483-496.
[17] Kaminski M, Rosen L, Gordon D, et al.Zoledronic acid versus pamidronate in patients with breast cancer and multiple myeloma who are at high risk for skeletal complications[J]. J Clin Oncol,2004,22(14):S857.
[18] Ferreira AR, Alho I, Shan N, et al.N-telopeptide of type Ⅰ collagen long-term dynamics in breast cancer patients with bone metastases: clinical outcomes and influence of extraskeletal metastases[J]. Oncologist,2016,21(12):1418-1426.
[19] Brown JE, Cook RJ, Lipton A, et al.Prognostic factors for skeletal complications from metastatic bone disease in breast cancer[J]. Breast Cancer Res Treat,2010,123(3):767-779.
[20] Amadori D, Aglietta M, Alessi B, et al.Efficacy and safety of 12-weekly versus 4-weekly zoledronic acid for prolonged treatment of patients with bone metastases from breast cancer(ZOOM): a phase 3, open-label, randomised, non-inferiority trial[J]. Lancet Oncol,2013,14(7):663-670.
[21] Amir E, Freedman O, Carlsson L, et al.Randomized feasibility study of de-escalated (every 12 wk) versus standard (every 3 to 4 wk) intravenous pamidronate in women with low-risk bone metastases from breast cancer[J]. J Clin Oncol,2013,36(5):436-442.
[22] Mathew A, Brufsky A.Bisphosphonates in breast cancer[J]. Int J Cancer,2015,137(4):753-764.
[23] Mathew A, Brufsky A.Breast cancer: zoledronic acid--more than just a bone drug[J]. Nat Rev Clin Oncol,2014,11(10):564-565.
