Personalized ctDNA detection and genomic profiling in the NeoRHEA Study

Circulating tumor DNA (ctDNA) is a promising biomarker in early hormone receptor (HR) + , HER2-negative breast cancer. We assessed ctDNA with the RaDaR assay in NeoRHEA (NCT03065621), a single-arm, phase II neoadjuvant palbociclib plus endocrine therapy trial over 4 months (4 × 28-day cycles). Plasma samples were drawn pre-treatment, after cycle 1, pre-surgery, and 1 month post-surgery. Baseline ctDNA was detected in 55%, fell to 5% during treatment, and was undetectable in all patients by 1-month post-surgery. Baseline detection was higher in grade 3 tumors, lower in multifocal/multicentric disease, and higher in residual cancer burden (RCB) 3. MYC gains/amplifications were enriched in ultrasound (US) responders, while PIK3CA gains were enriched in US non-responders; FAT1 losses were enriched in RCB 3. Baseline ctDNA predicted poor response to this regimen, supporting ctDNA as a biomarker to guide treatment in HR + /HER2-negative disease. Trial registration: EU Clinical Trials Register (EudraCT 2016-000879-24; registered 15 February 2017).

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Publication Details

Journal
npj Breast Cancer
Published
2025-12-05
DOI
https://doi.org/10.1038/s41523-025-00852-6
Primary Topic
Advanced Breast Cancer Therapies
Type
article
Field-Weighted Citation Impact
0.00

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Personalized ctDNA detection and genomic profiling in the NeoRHEA Study

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npj Breast Cancer
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Personalized ctDNA detection and genomic profiling in the NeoRHEA Study

Andreas Papagiannis, Mariana Brandão, Patrick Neven, Alexandra Stanciu, François P. Duhoux, Laurence Buisseret, Peter Vuylsteke, Nathan R. Campbell, Françoise Rothé, Christos Sotiriou, Marianne Paesmans, Michail Ignatiadis, Donatienne Taylor, Lieveke Ameye, Elisa Agostinetto, Christodoulos P. Pipinikas, A. Chevalier, Tatiana Besse
article en

Abstract

Circulating tumor DNA (ctDNA) is a promising biomarker in early hormone receptor (HR) + , HER2-negative breast cancer. We assessed ctDNA with the RaDaR assay in NeoRHEA (NCT03065621), a single-arm, phase II neoadjuvant palbociclib plus endocrine therapy trial over 4 months (4 × 28-day cycles). Plasma samples were drawn pre-treatment, after cycle 1, pre-surgery, and 1 month post-surgery. Baseline ctDNA was detected in 55%, fell to 5% during treatment, and was undetectable in all patients by 1-month post-surgery. Baseline detection was higher in grade 3 tumors, lower in multifocal/multicentric disease, and higher in residual cancer burden (RCB) 3. MYC gains/amplifications were enriched in ultrasound (US) responders, while PIK3CA gains were enriched in US non-responders; FAT1 losses were enriched in RCB 3. Baseline ctDNA predicted poor response to this regimen, supporting ctDNA as a biomarker to guide treatment in HR + /HER2-negative disease. Trial registration: EU Clinical Trials Register (EudraCT 2016-000879-24; registered 15 February 2017).

npj Breast CancerVol. 11(1)
Cliniques Universitaires Saint-Luc (BE), Université Libre de Bruxelles (BE), University of Namur (BE), Universitair Ziekenhuis Leuven (BE), Institut Jules Bordet (BE), CHU Dinant Godinne UCL Namur (BE), Centre Hospitalier Universitaire Brugmann (BE), NeoGenomics (United States) (US)
Pfizer
Openalex Percentile: Top 43%
Advanced Breast Cancer Therapies
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