Plasma ctDNA TP53 Mutation and Breast Cancer Prognosis: A Systematic Review and Meta-Analysis

ObjectiveTo analyze the association between plasma circulating tumor DNA (ctDNA) TP53 mutation status and survival outcomes in breast cancer patients.MethodsPubMed, Embase, and the Cochrane Library were searched for relevant literature published between 2000 and 2025, examining the impact of plasma...

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Main Authors: FAN Hao, LIANG Annan, ZOU Wei, GAO Guangxi, LIU Lijin, LIU Fei, ZHAO Lina, WU Zhihong
Format: Article
Language:zho
Published: Editorial Office of Medical Journal of Peking Union Medical College Hospital 2025-07-01
Series:Xiehe Yixue Zazhi
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Online Access:https://xhyxzz.pumch.cn/article/doi/10.12290/xhyxzz.2025-0434
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author FAN Hao
LIANG Annan
ZOU Wei
GAO Guangxi
LIU Lijin
LIU Fei
ZHAO Lina
WU Zhihong
author_facet FAN Hao
LIANG Annan
ZOU Wei
GAO Guangxi
LIU Lijin
LIU Fei
ZHAO Lina
WU Zhihong
author_sort FAN Hao
collection DOAJ
description ObjectiveTo analyze the association between plasma circulating tumor DNA (ctDNA) TP53 mutation status and survival outcomes in breast cancer patients.MethodsPubMed, 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.ResultsA total of 14 studies (13 cohort studies and 1 randomized controlled trial) involving 3521 breast cancer patients were included, among whom 921 had TP53 mutations.All studies were assessed as high-quality or low-risk.The random-effects model demonstrated that TP53 mutations were significantly associated with poorer OS (I2=77%, HR=1.82, 95% CI: 1.15-2.88, P=0.010), PFS (I2=63%, HR=1.68, 95% CI: 1.30-2.17, P < 0.001), and DFS (I2=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 stability 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/advanced 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).ConclusionPlasma 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 management and prognostic assessment.
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language zho
publishDate 2025-07-01
publisher Editorial Office of Medical Journal of Peking Union Medical College Hospital
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series Xiehe Yixue Zazhi
spelling doaj-art-256523d4e4de4489befaacf7845ea9792025-08-20T04:00:28ZzhoEditorial Office of Medical Journal of Peking Union Medical College HospitalXiehe Yixue Zazhi1674-90812025-07-0116487488510.12290/xhyxzz.2025-0434Plasma ctDNA TP53 Mutation and Breast Cancer Prognosis: A Systematic Review and Meta-AnalysisFAN Hao0LIANG AnnanZOU WeiGAO Guangxi1LIU Lijin2LIU Fei3ZHAO LinaWU ZhihongStem Cell Facility, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, ChinaStem Cell Facility, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, ChinaStem Cell Facility, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, ChinaStem Cell Facility, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, ChinaObjectiveTo analyze the association between plasma circulating tumor DNA (ctDNA) TP53 mutation status and survival outcomes in breast cancer patients.MethodsPubMed, 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.ResultsA total of 14 studies (13 cohort studies and 1 randomized controlled trial) involving 3521 breast cancer patients were included, among whom 921 had TP53 mutations.All studies were assessed as high-quality or low-risk.The random-effects model demonstrated that TP53 mutations were significantly associated with poorer OS (I2=77%, HR=1.82, 95% CI: 1.15-2.88, P=0.010), PFS (I2=63%, HR=1.68, 95% CI: 1.30-2.17, P < 0.001), and DFS (I2=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 stability 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/advanced 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).ConclusionPlasma 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 management and prognostic assessment.https://xhyxzz.pumch.cn/article/doi/10.12290/xhyxzz.2025-0434tp53 mutationsbreast cancerctdnaprognosismeta-analysis
spellingShingle FAN Hao
LIANG Annan
ZOU Wei
GAO Guangxi
LIU Lijin
LIU Fei
ZHAO Lina
WU Zhihong
Plasma ctDNA TP53 Mutation and Breast Cancer Prognosis: A Systematic Review and Meta-Analysis
Xiehe Yixue Zazhi
tp53 mutations
breast cancer
ctdna
prognosis
meta-analysis
title Plasma ctDNA TP53 Mutation and Breast Cancer Prognosis: A Systematic Review and Meta-Analysis
title_full Plasma ctDNA TP53 Mutation and Breast Cancer Prognosis: A Systematic Review and Meta-Analysis
title_fullStr Plasma ctDNA TP53 Mutation and Breast Cancer Prognosis: A Systematic Review and Meta-Analysis
title_full_unstemmed Plasma ctDNA TP53 Mutation and Breast Cancer Prognosis: A Systematic Review and Meta-Analysis
title_short Plasma ctDNA TP53 Mutation and Breast Cancer Prognosis: A Systematic Review and Meta-Analysis
title_sort plasma ctdna tp53 mutation and breast cancer prognosis a systematic review and meta analysis
topic tp53 mutations
breast cancer
ctdna
prognosis
meta-analysis
url https://xhyxzz.pumch.cn/article/doi/10.12290/xhyxzz.2025-0434
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AT liangannan plasmactdnatp53mutationandbreastcancerprognosisasystematicreviewandmetaanalysis
AT zouwei plasmactdnatp53mutationandbreastcancerprognosisasystematicreviewandmetaanalysis
AT gaoguangxi plasmactdnatp53mutationandbreastcancerprognosisasystematicreviewandmetaanalysis
AT liulijin plasmactdnatp53mutationandbreastcancerprognosisasystematicreviewandmetaanalysis
AT liufei plasmactdnatp53mutationandbreastcancerprognosisasystematicreviewandmetaanalysis
AT zhaolina plasmactdnatp53mutationandbreastcancerprognosisasystematicreviewandmetaanalysis
AT wuzhihong plasmactdnatp53mutationandbreastcancerprognosisasystematicreviewandmetaanalysis