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).
Authors
- Andreas Papagiannis
- Mariana Brandão (ORCID: https://orcid.org/0000-0002-1653-3544)
- Patrick Neven (ORCID: https://orcid.org/0000-0002-1434-9460)
- Alexandra Stanciu (ORCID: https://orcid.org/0000-0002-5866-4200)
- François P. Duhoux (ORCID: https://orcid.org/0000-0002-5429-7888)
- Laurence Buisseret (ORCID: https://orcid.org/0000-0002-3751-0819)
- Peter Vuylsteke (ORCID: https://orcid.org/0000-0001-6401-3722)
- Nathan R. Campbell (ORCID: https://orcid.org/0000-0002-3061-5693)
- Françoise Rothé (ORCID: https://orcid.org/0009-0003-2625-5642)
- Christos Sotiriou (ORCID: https://orcid.org/0000-0002-5745-9977)
- Marianne Paesmans
- Michail Ignatiadis (ORCID: https://orcid.org/0000-0002-4493-3748)
- Donatienne Taylor (ORCID: https://orcid.org/0000-0002-5141-513X)
- Lieveke Ameye (ORCID: https://orcid.org/0000-0001-5153-1766)
- Elisa Agostinetto (ORCID: https://orcid.org/0000-0003-0295-7511)
- Christodoulos P. Pipinikas (ORCID: https://orcid.org/0000-0002-9401-6550)
- A. Chevalier
- Tatiana Besse
Institutions
- 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)
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
Funders
- Pfizer