Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial
Abstract 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 exp...
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| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-025-00777-0 |
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| author | Joan Albanell Angelo Gámez Pozo Carlos L. Arteaga Meritxell Bellet Federico Rojo Abel González Beatriz Bellosillo Violeta Serra Petra Gener José Antonio Guerrero Eileen Shimizu Mario Mancino Jose Rodríguez-Morató Leonardo Mina José Manuel Pérez-García Javier Cortés Antonio Llombart-Cussac |
| author_facet | Joan Albanell Angelo Gámez Pozo Carlos L. Arteaga Meritxell Bellet Federico Rojo Abel González Beatriz Bellosillo Violeta Serra Petra Gener José Antonio Guerrero Eileen Shimizu Mario Mancino Jose Rodríguez-Morató Leonardo Mina José Manuel Pérez-García Javier Cortés Antonio Llombart-Cussac |
| author_sort | Joan Albanell |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-0ea7b05dbd08417c804f6f914f39711f |
| institution | Kabale University |
| issn | 2374-4677 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-0ea7b05dbd08417c804f6f914f39711f2025-08-20T03:47:17ZengNature Portfolionpj Breast Cancer2374-46772025-06-011111910.1038/s41523-025-00777-0Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trialJoan Albanell0Angelo Gámez Pozo1Carlos L. Arteaga2Meritxell Bellet3Federico Rojo4Abel González5Beatriz Bellosillo6Violeta Serra7Petra Gener8José Antonio Guerrero9Eileen Shimizu10Mario Mancino11Jose Rodríguez-Morató12Leonardo Mina13José Manuel Pérez-García14Javier Cortés15Antonio Llombart-Cussac16Hospital del Mar Research Institute Barcelona, Depatment of Medical Oncology, Hospital del MarTranslational Oncology Lab, University Hospital La Paz - IdiPAZUT Southwestern Simmons Comprehensive Cancer CenterVall d’Hebron Institute of OncologyHospital del Mar Research Institute Barcelona, Depatment of Medical Oncology, Hospital del MarHospital del Mar Research Institute Barcelona, Depatment of Medical Oncology, Hospital del MarHospital del Mar Research Institute Barcelona, Depatment of Medical Oncology, Hospital del MarVall d’Hebron Institute of OncologyMedica Scientia Innovation Research (MEDSIR) - Oncoclínicas&CoMedica Scientia Innovation Research (MEDSIR) - Oncoclínicas&CoMedica Scientia Innovation Research (MEDSIR) - Oncoclínicas&CoMedica Scientia Innovation Research (MEDSIR) - Oncoclínicas&CoMedica Scientia Innovation Research (MEDSIR) - Oncoclínicas&CoMedica Scientia Innovation Research (MEDSIR) - Oncoclínicas&CoMedica Scientia Innovation Research (MEDSIR) - Oncoclínicas&CoMedica Scientia Innovation Research (MEDSIR) - Oncoclínicas&CoMedica Scientia Innovation Research (MEDSIR) - Oncoclínicas&CoAbstract 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.https://doi.org/10.1038/s41523-025-00777-0 |
| spellingShingle | Joan Albanell Angelo Gámez Pozo Carlos L. Arteaga Meritxell Bellet Federico Rojo Abel González Beatriz Bellosillo Violeta Serra Petra Gener José Antonio Guerrero Eileen Shimizu Mario Mancino Jose Rodríguez-Morató Leonardo Mina José Manuel Pérez-García Javier Cortés Antonio Llombart-Cussac Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial npj Breast Cancer |
| title | Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial |
| title_full | Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial |
| title_fullStr | Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial |
| title_full_unstemmed | Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial |
| title_short | Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial |
| title_sort | biomarkers of palbociclib response in hormone receptor positive advanced breast cancer from the parsifal trial |
| url | https://doi.org/10.1038/s41523-025-00777-0 |
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