Sistema de Salut de Catalunya
Institut Català de la Salut
[Albanell J] Hospital del Mar Research Institute Barcelona, Depatment of Medical Oncology, Hospital del Mar, Barcelona, Spain. Universitat Pompeu Fabra, Barcelona, Spain. Centro de Investigación Biomédica en Red de Oncología (CIBERONC-ISCIII), Madrid, Spain. [Gámez Pozo A] Translational Oncology Lab, University Hospital La Paz - IdiPAZ, Madrid, Spain. [Arteaga CL] UT Southwestern Simmons Comprehensive Cancer Center, Dallas, TX, USA. [Bellet M] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Rojo F, González A] Hospital del Mar Research Institute Barcelona, Depatment of Medical Oncology, Hospital del Mar, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-08-12T07:57:37Z
2025-08-12T07:57:37Z
2025-06-20
Biomarkers; Hormone receptor-positive; Advanced breast cancer
Biomarcadores; Cáncer de mama avanzado; Receptor hormonal positivo
Biomarcadors; Càncer de mama avançat; Receptor hormonal positiu
Currently, there are no clinically actionable biomarkers to predict patient to cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) plus endocrine therapy for hormone receptor (HR)[+]/ human epidermal growth factor receptor 2 (HER2)[-] advanced breast cancer (ABC). Herein, we report an exploratory biomarker substudy (transFAL) from a subset of patients included in PARSIFAL, a phase II randomized clinical trial that evaluated first-line palbociclib plus fulvestrant or letrozole for HR[+]/HER2[−] ABC. No definitive biomarkers were discovered, however, worse outcomes were found with CDK6 postivity (p = 0.008), ER negativity (p = 0.008), high Ki67 (p = 0.04), and TP53 mutation (p = 0.04). ctDNA density (p = 0.036) and number of mutations (p = 0.033) at baseline were significantly higher for resistant patients. Our study reveals future directions to explore in the goal to determine biomarkers of response to CDK4/6i.
Article
Published version
English
Marcadors bioquímics; Proteïnes quinases - Inhibidors - Ús terapèutic; Mama - Càncer - Tractament; Quimioteràpia combinada; CHEMICALS AND DRUGS::Biological Factors::Biomarkers; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors; Other subheadings::Other subheadings::/therapeutic use; DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols; COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas; Otros calificadores::Otros calificadores::/uso terapéutico; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada
Nature Portfolio
npj Breast Cancer;11
https://doi.org/10.1038/s41523-025-00777-0
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
