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
{"title":"PARSIFAL试验中帕博西尼对激素受体阳性晚期乳腺癌反应的生物标志物。","authors":"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","doi":"10.1038/s41523-025-00777-0","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"59"},"PeriodicalIF":7.6000,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181395/pdf/","citationCount":"0","resultStr":"{\"title\":\"Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial.\",\"authors\":\"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\",\"doi\":\"10.1038/s41523-025-00777-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":19247,\"journal\":{\"name\":\"NPJ Breast Cancer\",\"volume\":\"11 1\",\"pages\":\"59\"},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2025-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181395/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"NPJ Breast Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41523-025-00777-0\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Breast Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41523-025-00777-0","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial.
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.
期刊介绍：
npj Breast Cancer publishes original research articles, reviews, brief correspondence, meeting reports, editorial summaries and hypothesis generating observations which could be unexplained or preliminary findings from experiments, novel ideas, or the framing of new questions that need to be solved. Featured topics of the journal include imaging, immunotherapy, molecular classification of disease, mechanism-based therapies largely targeting signal transduction pathways, carcinogenesis including hereditary susceptibility and molecular epidemiology, survivorship issues including long-term toxicities of treatment and secondary neoplasm occurrence, the biophysics of cancer, mechanisms of metastasis and their perturbation, and studies of the tumor microenvironment.
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