The Prognostic and Predictive Impact of Circulating Tumour DNA Levels in Patients with Advanced Breast Cancer Enrolled on the plasmaMATCH Trial Article Swipe
Iseult Browne
,
Javier Pascual
,
Rosalind J. Cutts
,
Belinda Kingston
,
Sarah Hrebien
,
Lucy Kilburn
,
Alex Pearson
,
Laura Moretti
,
Andrew Wardley
,
Iain R. Macpherson
,
Richard D. Baird
,
Rebecca Roylance
,
Miguel Gil‐Gil
,
Ángel Guerrero‐Zotano
,
Isaac García-Murillas
,
Judith M. Bliss
,
Alistair Ring
,
Miguel Martín
,
Nicholas C. Turner
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.ccr-24-0651
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.ccr-24-0651
Purpose: Circulating tumour DNA(ctDNA) dynamic levels may identify patients who will respond to therapy. We assessed ctDNA baseline levels and on-treatment dynamics in advanced breast cancer patients on the plasmaMATCH trial with mutation targeted therapies(cohorts A-D),and triple-negative breast cancer(TNBC) on olaparib and ceralasertib combination(cohort E). Experimental Design: Blood samples were collected at baseline(C1D1),and before treatment on cycle2day1(C2D1). Samples were sequenced using error-corrected targeted panels(Guardant360/GuardantOMNI). Circulating DNA ratio(CDR) was calculated as the ratio of C2D1/C1D1.CDR, and baseline ctDNA levels,were associated with progression free survival (PFS) and confirmed objective response rates (ORR). Results: 167 patients had assessable C1D1-C2D1 ctDNA results. There was a strong association between baseline ctDNA levels and response in cohort E;low baseline levels were associated with longer PFS (HR 0.33,p=0.001),and higher ORR (40%vs9.7%,p=0.02). In cohorts A-D there was a weaker association with PFS(HR0.60,p=0.03) and ORR(15.2%vs5.7%,p=0.17). Associations of baseline ctDNA level and ORR were validated in the independent PEARL study. For on-treatment dynamics, suppression of ctDNA below median was predictive in cohorts A-D (HR0.47, p=0.001), but not in cohort E(HR1.02, p=0.94). Undetectable ctDNA levels at C2D1 was associated with good outcomes in both cohorts, in cohort E with improved PFS(HR0.25,p=0.01) and improved ORR(86%vs11%,p=0.01). 6/7 patients with undetectable on-treatment ctDNA were BRCA1/BRCA2/PALB2 wildtype. Conclusions: Baseline low ctDNA levels predict response to targeted therapy, potentially suggesting shared mechanisms between high ctDNA release and resistance to therapy. Both baseline ctDNA levels and on-treatment dynamics are a promising surrogate endpoint for drug development, with clearance of ctDNA being a robust cross-therapy surrogate for outcome.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1158/1078-0432.ccr-24-0651
- https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-24-0651/3666326/ccr-24-0651.pdf
- OA Status
- hybrid
- OpenAlex ID
- https://openalex.org/W4415664944
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4415664944Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1158/1078-0432.ccr-24-0651Digital Object Identifier
- Title
-
The Prognostic and Predictive Impact of Circulating Tumour DNA Levels in Patients with Advanced Breast Cancer Enrolled on the plasmaMATCH TrialWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-10-29Full publication date if available
- Authors
-
Iseult Browne, Javier Pascual, Rosalind J. Cutts, Belinda Kingston, Sarah Hrebien, Lucy Kilburn, Alex Pearson, Laura Moretti, Andrew Wardley, Iain R. Macpherson, Richard D. Baird, Rebecca Roylance, Miguel Gil‐Gil, Ángel Guerrero‐Zotano, Isaac García-Murillas, Judith M. Bliss, Alistair Ring, Miguel Martín, Nicholas C. TurnerList of authors in order
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-
https://doi.org/10.1158/1078-0432.ccr-24-0651Publisher landing page
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https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-24-0651/3666326/ccr-24-0651.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
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https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-24-0651/3666326/ccr-24-0651.pdfDirect OA link when available
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