| Autor: |
Martínez-Rodríguez A; 'Clinical and Translational Research in Oncology' Group, Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain.; Department of Medical Oncology, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain., Fuentes-Antrás J; Department of Medical Oncology, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain.; NEXT Oncology Experimental Therapeutics Unit, Hospital Universitario Quironsalud Madrid, 28223 Madrid, Spain., Lorca V; 'Clinical and Translational Research in Oncology' Group, Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain., López de Sá A; Department of Medical Oncology, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain., Pérez-Segura P; Department of Medical Oncology, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain., Moreno F; Department of Medical Oncology, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain., García-Sáenz JA; Department of Medical Oncology, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain., García-Barberán V; 'Clinical and Translational Research in Oncology' Group, Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain. |
| Abstrakt: |
Standard treatments in hormone receptor-positive (HR+)/HER2-metastatic breast cancer (mBC) typically involve endocrine therapy (ET) combined with CDK4/6 inhibitors, yet resistance to ET remains a persistent challenge in advanced cases. A deeper knowledge of the use of liquid biopsy is crucial for the implementation of precision medicine in mBC with real-time treatment guidance. Our study assesses the prognostic value of PIK3CA and ESR1 mutations in DNA derived from extracellular vesicles (EV-DNA) in longitudinal plasma from 59 HR+/HER2-mBC patients previously exposed to aromatase inhibitors, with a comparative analysis against circulating tumor DNA (ctDNA). Mutations were evaluated by digital PCR. PIK3CA and ESR1 mutations were found in 22 and 25% of patients. Baseline ESR1 mutations in EV-DNA were associated with shorter progression-free survival (PFS) across the cohort, with the Y537S mutation showing a particularly strong impact on the outcome of fulvestrant-treated patients. In contrast, PIK3CA mutations in EV-DNA did not significantly correlate with PFS, whereas in ctDNA, they were linked to poor outcomes. Altogether, this study positions EV-DNA as a valuable biomarker alongside ctDNA, enriching the understanding of different analytes in liquid biopsy and supporting strategies for HR+/HER2-mBC in precision oncology. |
