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NeoCircle : pre- and post-operative circulating tumor DNA dynamics predicts survival in neoadjuvant-treated early breast cancer

George, Anthony M LU ; Chen, Yilun LU ; Gladchuk, Sergii LU ; Alcaide, Miguel ; Dalal, Hina LU orcid ; Meng, Pei LU ; Brueffer, Christian LU orcid ; Saghir, Hani LU ; Kimbung, Siker LU and Aaltonen, Kristina LU orcid , et al. (2026) In EMBO Molecular Medicine p.1-18
Abstract

Persistent circulating tumor DNA (ctDNA) during neoadjuvant treatment (NAT) of early breast cancer (EBC) indicates high-risk disease. Similarly, detection of ctDNA post-resection indicates molecular residual disease (MRD) and impending relapse. For ctDNA to be integrated into EBC management, accessible and scalable diagnostics are required. Here we apply an ultrasensitive, personalized tumor-informed approach to ctDNA evaluation predicated on analyses of structural variants (SVs) using a novel digital PCR (dPCR) multiplex SV technology. 136 patients eligible for NAT (29.4% TNBC, 44.9% HR+ /HER2- and 24.3% HER2+), enrolled between December 2014 and March 2019, were analyzed from the prospective SCAN-B study (NCT02306096, substudy... (More)

Persistent circulating tumor DNA (ctDNA) during neoadjuvant treatment (NAT) of early breast cancer (EBC) indicates high-risk disease. Similarly, detection of ctDNA post-resection indicates molecular residual disease (MRD) and impending relapse. For ctDNA to be integrated into EBC management, accessible and scalable diagnostics are required. Here we apply an ultrasensitive, personalized tumor-informed approach to ctDNA evaluation predicated on analyses of structural variants (SVs) using a novel digital PCR (dPCR) multiplex SV technology. 136 patients eligible for NAT (29.4% TNBC, 44.9% HR+ /HER2- and 24.3% HER2+), enrolled between December 2014 and March 2019, were analyzed from the prospective SCAN-B study (NCT02306096, substudy NeoCircle). ctDNA detection at baseline was 89.7%; end-NAT ctDNA-positivity (21.4%) and NAT ctDNA-non-response (13.1%) were significant predictors of disease recurrence and death, and both superior to pathologic complete response. Detection of ctDNA post-operatively or during adjuvant monitoring was significantly associated with distant recurrence (median lead-time 13.8 months, range 0-47.7 months). These findings validate SVs as an MRD analyte and provide evidence for clinical use of this approach in EBC.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
EMBO Molecular Medicine
pages
1 - 18
publisher
Wiley-Blackwell
external identifiers
  • scopus:105040193160
  • pmid:42192203
ISSN
1757-4684
DOI
10.1038/s44321-026-00447-z
language
English
LU publication?
yes
additional info
© 2026. The Author(s).
id
0e854bd3-53ae-4f35-b576-b18d76f5f0e3
date added to LUP
2026-06-22 11:30:40
date last changed
2026-07-22 12:40:25
@article{0e854bd3-53ae-4f35-b576-b18d76f5f0e3,
  abstract     = {{<p>Persistent circulating tumor DNA (ctDNA) during neoadjuvant treatment (NAT) of early breast cancer (EBC) indicates high-risk disease. Similarly, detection of ctDNA post-resection indicates molecular residual disease (MRD) and impending relapse. For ctDNA to be integrated into EBC management, accessible and scalable diagnostics are required. Here we apply an ultrasensitive, personalized tumor-informed approach to ctDNA evaluation predicated on analyses of structural variants (SVs) using a novel digital PCR (dPCR) multiplex SV technology. 136 patients eligible for NAT (29.4% TNBC, 44.9% HR+ /HER2- and 24.3% HER2+), enrolled between December 2014 and March 2019, were analyzed from the prospective SCAN-B study (NCT02306096, substudy NeoCircle). ctDNA detection at baseline was 89.7%; end-NAT ctDNA-positivity (21.4%) and NAT ctDNA-non-response (13.1%) were significant predictors of disease recurrence and death, and both superior to pathologic complete response. Detection of ctDNA post-operatively or during adjuvant monitoring was significantly associated with distant recurrence (median lead-time 13.8 months, range 0-47.7 months). These findings validate SVs as an MRD analyte and provide evidence for clinical use of this approach in EBC.</p>}},
  author       = {{George, Anthony M and Chen, Yilun and Gladchuk, Sergii and Alcaide, Miguel and Dalal, Hina and Meng, Pei and Brueffer, Christian and Saghir, Hani and Kimbung, Siker and Aaltonen, Kristina and Oton, Lucia and Rushton, Christopher and Birkeälv, Sofia and Jönsson, Mats and Zackrisson, Sophia and Skarping, Ida and Förnvik, Daniel and Zander, Lina and Honeth, Gabriella and Woodhouse, Samuel and Howarth, Karen and Borg, Åke and Ehinger, Anna and Malmberg, Martin and Rydén, Lisa and Loman, Niklas and Saal, Lao H}},
  issn         = {{1757-4684}},
  language     = {{eng}},
  month        = {{05}},
  pages        = {{1--18}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{EMBO Molecular Medicine}},
  title        = {{NeoCircle : pre- and post-operative circulating tumor DNA dynamics predicts survival in neoadjuvant-treated early breast cancer}},
  url          = {{http://dx.doi.org/10.1038/s44321-026-00447-z}},
  doi          = {{10.1038/s44321-026-00447-z}},
  year         = {{2026}},
}