摘要
目的分析血浆循环肿瘤DNA(circulating tumor DNA,ctDNA)TP53突变状态与乳腺癌患者生存预后的关系。方法检索PubMed、Embase和Cochrane Library数据库,获取2000—2025年血浆ctDNA TP53突变对乳腺癌患者生存结局影响的相关文献,指标包括总生存期(overall survival,OS)、无进展生存期(progression⁃free survival,PFS)或无病生存期(disease⁃free survival,DFS)。由2名研究人员按照纳入与排除标准对文献进行筛选,并提取相关数据。采用纽卡斯尔⁃渥太华量表和Cochrane风险偏倚评估工具评估文献质量,并通过Review Manager 5.3和STATA 18.0软件进行Meta分析、发表偏倚评价和敏感性分析。结果最终纳入14篇文献(队列研究13篇,随机对照试验1篇),包含3521例乳腺癌患者,其中TP53突变型921例。经评估,所有文献均为高质量或低风险研究。随机效应模型显示,TP53突变与较差的OS(I^(2)=77%,HR=1.82,95%CI:1.15~2.88,P=0.010)、PFS(I^(2)=63%,HR=1.68,95%CI:1.30~2.17,P<0.001)和DFS(I^(2)=85%,HR=1.98,95%CI:1.05~3.75,P=0.040)均显著相关。漏斗图显示,相关研究未发现明显的发表偏倚;敏感性分析显示,结果具有稳定性和可信度。根据研究设计、乳腺癌患者分期、分子亚型进行亚组分析,结果显示,在前瞻性研究(OS:HR=2.32,95%CI:1.84~2.92,P<0.001;PFS:HR=1.83,95%CI:1.47~2.27,P<0.001)、转移性/晚期乳腺癌(OS:HR=2.03,95%CI:1.44~2.87,P<0.001;PFS:HR=1.90,95%CI:1.57~2.31,P<0.001)、激素受体+人表皮生长因子受体2-(OS:HR=2.11,95%CI:1.56~2.85,P<0.001;PFS:HR=1.94,95%CI:1.62~2.33,P<0.001)患者中,血浆ctDNA TP53突变均与较差的预后相关。在不同治疗方案方面,曲妥珠单抗联合紫杉醇治疗组血浆ctDNA TP53突变患者的预后相对更好(PFS:HR=0.08,95%CI:0.02~0.30,P<0.001)。结论血浆ctDNA TP53突变与乳腺癌患者生存结局密切相关,有望作为预后不良的潜在预测因子,为乳腺癌患者的临床管理和预后评估提供支持。
Objective To analyze the association between plasma circulating tumor DNA(ctDNA)TP53 mutation status and survival outcomes in breast cancer patients.Methods PubMed,Embase,and the Cochrane Library were searched for relevant literature published between 2000 and 2025,examining the impact of plasma ctDNA TP53 mutations on survival outcomes in breast cancer patients,including overall survival(OS),progression⁃free survival(PFS),or disease⁃free survival(DFS).Two researchers independently screened the literature according to predefined inclusion and exclusion criteria and extracted relevant data.The Newcastle⁃Ottawa scale and Cochrane Risk of Bias Assessment Tool were used to evaluate study quality.Meta⁃analysis,publication bias assessment,and sensitivity analysis were performed using Review Manager 5.3 and STATA 18.0 software.Results A total of 14 studies(13 cohort studies and 1 randomized controlled trial)in⁃volving 3521 breast cancer patients were included,among whom 921 had TP53 mutations.All studies were as⁃sessed as high⁃quality or low⁃risk.The random⁃effects model demonstrated that TP53 mutations were significantly associated with poorer OS(I^(2)=77%,HR=1.82,95%CI:1.15-2.88,P=0.010),PFS(I^(2)=63%,HR=1.68,95%CI:1.30-2.17,P<0.001),and DFS(I^(2)=85%,HR=1.98,95%CI:1.05-3.75,P=0.040).Funnel plots indicated no significant publication bias,and sensitivity analysis confirmed the stabil⁃ity and reliability of the results.Subgroup analyses based on study design,breast cancer stage and molecular subtype revealed that TP53 mutations were associated with worse prognosis in prospective studies(OS:HR=2.32,95%CI:1.84-2.92,P<0.001;PFS:HR=1.83,95%CI:1.47-2.27,P<0.001),metastatic/ad⁃vanced breast cancer(OS:HR=2.03,95%CI:1.44-2.87,P<0.001;PFS:HR=1.90,95%CI:1.57-2.31,P<0.001),and hormone receptor⁃positive and human epidermal growth factor receptor 2⁃negative(HR+HER2-)patients(OS:HR=2.11,95%CI:1.56-2.85,P<0.001;PFS:HR=1.94,95%CI:1.62-2.33,P<0.001).Among different treatment regimens,patients with TP53 mutations receiving trastuzumab combined with paclitaxel exhibited relatively better prognosis(PFS:HR=0.08,95%CI:0.02-0.30,P<0.001).Conclusion Plasma ctDNA TP53 mutations are closely associated with survival outcomes in breast cancer patients and may serve as a potential predictor of poor prognosis,providing support for clinical manage⁃ment and prognostic assessment.
作者
樊浩
梁安南
邹伟
高广西
刘理金
刘菲
赵丽娜
吴志宏
FAN Hao;LIANG Annan;ZOU Wei;GAO Guangxi;LIU Lijin;LIU Fei;ZHAO Lina;WU Zhihong(Stem Cell Facility,Institute of Clinical Medicine,Peking Union Medical College Hospital Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Department of Orthopedic Surgery,Peking Union Medical College Hospital Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Graduate School,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China)
出处
《协和医学杂志》
北大核心
2025年第4期874-885,共12页
Medical Journal of Peking Union Medical College Hospital
基金
中国工程院国家自然科学基金委联合战略研究与咨询项目(2024⁃ZCQ⁃18)
国家自然科学基金(82172525,82402760)
北京市自然科学基金青年项目(7244389)
中国医学科学院医学与健康科技创新工程重大协同创新项目(2021⁃I2M⁃1⁃052)
中央高水平医院临床科研专项(2022⁃PUMCH⁃D⁃002)。
作者简介
通信作者:赵丽娜,E⁃mail:zhaolina19921125@163.com;通信作者:吴志宏,E⁃mail:wuzh3000@126.com。
