HER2DX ERBB2 mRNA score in first-line advanced HER2-positive breast cancer treated with chemotherapy, trastuzumab, and pertuzumab
In advanced HER2-positive breast cancer, the standard taxane-trastuzumab-pertuzumab (THP) regimen faces competition from new therapies, emphasizing the need for biomarkers to guide treatment. This study evaluates the HER2DX ERBB2 mRNA score as a prognostic predictor, aiming to tailor treatment strategies. We retrospectively analyzed 94 patients treated with the THP regimen between 2010 and 2024. The HER2DX ERBB2 mRNA score was categorized as low (n = 14), medium (n = 20), or high (n = 60), and its correlation with progression-free survival (PFS) and overall survival (OS) was assessed using Cox regression models. The median follow-up was 31.5 months. Patients with ERBB2-high scores had significantly better median PFS (33.9 vs. 10.6 months, hazard ratio [HR] = 0.40, 95% CI: 0.24-0.69, p < 0.001) and OS (not reached vs. 30.8 months, HR = 0.26, 95% CI: 0.13-0.49, p < 0.001) compared to ERBB2-low patients. Based on these findings, further validation of this biomarker in tumor samples from the CLEOPATRA phase III trial is ongoing, which could help optimize treatment strategies in this population.
Authors
- Oleguer Castillo
- Pablo Tolosa (ORCID: https://orcid.org/0000-0002-3747-4766)
- Valeria Sirenko
- Esther Carcelero
- Fara Brasó‐Maristany (ORCID: https://orcid.org/0000-0001-5440-9643)
- Angela Aguirre (ORCID: https://orcid.org/0009-0003-0723-0052)
- Guillermo Villacampa (ORCID: https://orcid.org/0000-0003-4868-6585)
- Cristina González-Deza
- Luís Manso (ORCID: https://orcid.org/0000-0002-1683-550X)
- Tomás Pascual (ORCID: https://orcid.org/0000-0001-8431-3183)
- Rodrigo Sánchez-Bayona (ORCID: https://orcid.org/0000-0002-5255-6620)
- Jesús Soberino (ORCID: https://orcid.org/0009-0004-4035-7669)
- Manuel Alva
- Patricia Galván (ORCID: https://orcid.org/0000-0002-8153-0307)
- Charles M. Perou (ORCID: https://orcid.org/0000-0001-9827-2247)
- Paula Blasco
- María Cobos-Fernández (ORCID: https://orcid.org/0009-0000-4821-4081)
- Olga Martínez‐Sáez (ORCID: https://orcid.org/0000-0001-8686-0236)
- Isabel García-Fructuoso (ORCID: https://orcid.org/0000-0002-7417-4703)
- Esther Sanfeliu (ORCID: https://orcid.org/0000-0002-7974-3346)
- Julia Maués (ORCID: https://orcid.org/0000-0002-4478-6952)
- Laia Paré (ORCID: https://orcid.org/0000-0002-4904-558X)
- Eva Ciruelos (ORCID: https://orcid.org/0000-0002-2796-1042)
- Patricia Villagrasa (ORCID: https://orcid.org/0000-0002-8662-3641)
- Wesley Buckingham (ORCID: https://orcid.org/0009-0006-4707-9803)
- Mercedes Marín‐Aguilera (ORCID: https://orcid.org/0000-0002-2205-3459)
- Aleix Prat (ORCID: https://orcid.org/0000-0003-2377-540X)
- Ainhoa Madariaga (ORCID: https://orcid.org/0000-0001-7166-9762)
- Elia Seguí (ORCID: https://orcid.org/0000-0001-7770-9825)
- Laura Lema (ORCID: https://orcid.org/0000-0001-8527-3398)
- María Rey
- Astrid Mayhua
- Denys Romero-Romero
Institutions
- Breast Cancer Research Foundation (US)
- Hospital Universitario 12 De Octubre (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Center for Cancer and Blood Disorders (US)
- Hospital Quirónsalud Barcelona (ES)
- Hospital Clínic de Barcelona (ES)
- Cancer Clinic (US)
- HM Hospitales (ES)
- Oryzon Genomics (Spain) (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2025-04-25
- DOI
- https://doi.org/10.1038/s41523-025-00753-8
- Citations
- 5
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 5.23
Funders
- Breast Cancer Research Foundation
- European Commission
- Fundación Científica Asociación Española Contra el Cáncer
- Fundación Fero
- Instituto de Salud Carlos III