Role of circulating tumor DNA in early-stage triple-negative breast cancer: a systematic review and meta-analysis

Abstract Background Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and carries a worse prognosis relative to other breast cancer subtypes. This systematic review and meta-analysis evaluated the prognostic value of circulating tumor DNA (ctDNA) in early-stage TNBC. Method...

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Main Authors: Diana Zhang, Shayesteh Jahanfar, Judy B. Rabinowitz, Joshua Dower, Fei Song, Cherng-Horng Wu, Xiao Hu, Phillip Tracy, Mark Basik, Arielle Medford, Po-Han Lin, Chiun-Sheng Huang, Francois-Clement Bidard, Shufang Renault, Lori Pai, Mary Buss, Heather A. Parsons, Ilana Schlam
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Language:English
Published: BMC 2025-03-01
Series:Breast Cancer Research
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Online Access:https://doi.org/10.1186/s13058-025-01986-y
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author Diana Zhang
Shayesteh Jahanfar
Judy B. Rabinowitz
Joshua Dower
Fei Song
Cherng-Horng Wu
Xiao Hu
Phillip Tracy
Mark Basik
Arielle Medford
Po-Han Lin
Chiun-Sheng Huang
Francois-Clement Bidard
Shufang Renault
Lori Pai
Mary Buss
Heather A. Parsons
Ilana Schlam
author_facet Diana Zhang
Shayesteh Jahanfar
Judy B. Rabinowitz
Joshua Dower
Fei Song
Cherng-Horng Wu
Xiao Hu
Phillip Tracy
Mark Basik
Arielle Medford
Po-Han Lin
Chiun-Sheng Huang
Francois-Clement Bidard
Shufang Renault
Lori Pai
Mary Buss
Heather A. Parsons
Ilana Schlam
author_sort Diana Zhang
collection DOAJ
description Abstract Background Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and carries a worse prognosis relative to other breast cancer subtypes. This systematic review and meta-analysis evaluated the prognostic value of circulating tumor DNA (ctDNA) in early-stage TNBC. Methods A literature search was conducted using Ovid Medline, Elsevier EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science Databases for publications up to 11/16/2023. Results were uploaded to Covidence and assessed by two independent reviewers. Studies assessing the use of ctDNA to predict recurrence free survival and related outcomes as well as overall survival were included. All recurrence outcomes were combined during analysis. Statistical analysis was performed using Revman Web. Log-hazard ratios (HR) were pooled for studies reporting recurrence and death as a time-to-event outcomes. Odds ratios (OR) were calculated and pooled for studies reporting patient-level data on recurrence, death, and pathological complete response (pCR). Prospero ID: CRD42023492529. Results A total of 3,526 publications were identified through our literature search, and 20 publications (n = 1202 patients) were included in the meta-analysis. In studies that reported recurrence as a time-to-event outcome, post-neoadjuvant (before or after surgery) ctDNA + status was associated with a higher likelihood of disease recurrence (HR 4.12, 95% confidence interval [CI] 2.81–6.04). For studies that reported patient-level data, post-neoadjuvant ctDNA + status was associated with higher odds of disease recurrence (OR 6.72, 95% CI 3.61–12.54). Pooled log-HR also revealed that ctDNA + status in the post-neoadjuvant setting (before or after surgery) was associated with worse overall survival (HR 3.26, 95% CI 1.88–5.63). Conclusions Our findings suggest that ctDNA could be used as a prognostic biomarker to anticipate the risk of relapse. However, it remains unclear if therapeutic intervention for patients who are ctDNA + can improve outcomes. While more studies are needed before incorporating ctDNA into clinical practice, the findings of this meta-analysis are reassuring and show the promise of ctDNA as a biomarker.
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spelling doaj-art-b30337abbd9c46ab9a09d1b3c1dae4fe2025-08-20T03:02:19ZengBMCBreast Cancer Research1465-542X2025-03-0127111210.1186/s13058-025-01986-yRole of circulating tumor DNA in early-stage triple-negative breast cancer: a systematic review and meta-analysisDiana Zhang0Shayesteh Jahanfar1Judy B. Rabinowitz2Joshua Dower3Fei Song4Cherng-Horng Wu5Xiao Hu6Phillip Tracy7Mark Basik8Arielle Medford9Po-Han Lin10Chiun-Sheng Huang11Francois-Clement Bidard12Shufang Renault13Lori Pai14Mary Buss15Heather A. Parsons16Ilana Schlam17Division of Hematology and Oncology, Tufts Medical CenterTufts University Medical School, Tufts Medical CenterTufts UniversityDivision of Hematology and Oncology, Tufts Medical CenterDivision of Hematology and Oncology, Tufts Medical CenterDivision of Hematology and Oncology, Tufts Medical CenterDivision of Hematology and Oncology, Tufts Medical CenterDivision of Hematology and Oncology, Tufts Medical CenterLady Davis Institute, Jewish General HospitalDepartment of Oncology, Massachusetts General HospitalNational Taiwan University Hospital, National Taiwan University College of MedicineNational Taiwan University Hospital, National Taiwan University College of MedicineCirculating Tumor Laboratory, Inserm CIC-BT 1428, Institut CurieCirculating Tumor Laboratory, Inserm CIC-BT 1428, Institut CurieDivision of Hematology and Oncology, Tufts Medical CenterDivision of Hematology and Oncology, Tufts Medical CenterHarvard Medical SchoolDivision of Hematology and Oncology, Tufts Medical CenterAbstract Background Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and carries a worse prognosis relative to other breast cancer subtypes. This systematic review and meta-analysis evaluated the prognostic value of circulating tumor DNA (ctDNA) in early-stage TNBC. Methods A literature search was conducted using Ovid Medline, Elsevier EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science Databases for publications up to 11/16/2023. Results were uploaded to Covidence and assessed by two independent reviewers. Studies assessing the use of ctDNA to predict recurrence free survival and related outcomes as well as overall survival were included. All recurrence outcomes were combined during analysis. Statistical analysis was performed using Revman Web. Log-hazard ratios (HR) were pooled for studies reporting recurrence and death as a time-to-event outcomes. Odds ratios (OR) were calculated and pooled for studies reporting patient-level data on recurrence, death, and pathological complete response (pCR). Prospero ID: CRD42023492529. Results A total of 3,526 publications were identified through our literature search, and 20 publications (n = 1202 patients) were included in the meta-analysis. In studies that reported recurrence as a time-to-event outcome, post-neoadjuvant (before or after surgery) ctDNA + status was associated with a higher likelihood of disease recurrence (HR 4.12, 95% confidence interval [CI] 2.81–6.04). For studies that reported patient-level data, post-neoadjuvant ctDNA + status was associated with higher odds of disease recurrence (OR 6.72, 95% CI 3.61–12.54). Pooled log-HR also revealed that ctDNA + status in the post-neoadjuvant setting (before or after surgery) was associated with worse overall survival (HR 3.26, 95% CI 1.88–5.63). Conclusions Our findings suggest that ctDNA could be used as a prognostic biomarker to anticipate the risk of relapse. However, it remains unclear if therapeutic intervention for patients who are ctDNA + can improve outcomes. While more studies are needed before incorporating ctDNA into clinical practice, the findings of this meta-analysis are reassuring and show the promise of ctDNA as a biomarker.https://doi.org/10.1186/s13058-025-01986-yCirculating tumor DNATriple-negative breast cancerPrognosisRecurrence-free survivalDisease free survivalOverall survival
spellingShingle Diana Zhang
Shayesteh Jahanfar
Judy B. Rabinowitz
Joshua Dower
Fei Song
Cherng-Horng Wu
Xiao Hu
Phillip Tracy
Mark Basik
Arielle Medford
Po-Han Lin
Chiun-Sheng Huang
Francois-Clement Bidard
Shufang Renault
Lori Pai
Mary Buss
Heather A. Parsons
Ilana Schlam
Role of circulating tumor DNA in early-stage triple-negative breast cancer: a systematic review and meta-analysis
Breast Cancer Research
Circulating tumor DNA
Triple-negative breast cancer
Prognosis
Recurrence-free survival
Disease free survival
Overall survival
title Role of circulating tumor DNA in early-stage triple-negative breast cancer: a systematic review and meta-analysis
title_full Role of circulating tumor DNA in early-stage triple-negative breast cancer: a systematic review and meta-analysis
title_fullStr Role of circulating tumor DNA in early-stage triple-negative breast cancer: a systematic review and meta-analysis
title_full_unstemmed Role of circulating tumor DNA in early-stage triple-negative breast cancer: a systematic review and meta-analysis
title_short Role of circulating tumor DNA in early-stage triple-negative breast cancer: a systematic review and meta-analysis
title_sort role of circulating tumor dna in early stage triple negative breast cancer a systematic review and meta analysis
topic Circulating tumor DNA
Triple-negative breast cancer
Prognosis
Recurrence-free survival
Disease free survival
Overall survival
url https://doi.org/10.1186/s13058-025-01986-y
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