Biomarkers of palbociclib response in hormone receptor-positive advanced breast cancer from the PARSIFAL trial.

IF 7.6 2区医学 Q1 ONCOLOGY

NPJ Breast Cancer Pub Date : 2025-06-20 DOI:10.1038/s41523-025-00777-0

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

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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.

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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。

目前，对于激素受体（HR）[+]/人表皮生长因子受体2 (HER2)[-]晚期乳腺癌（ABC），尚无临床可操作的生物标志物来预测患者对周期蛋白依赖性激酶4和6抑制剂（CDK4/6i）加内分泌治疗的反应。在此，我们报告了一项探索性生物标志物亚研究（transal），该研究来自PARSIFAL的一组患者，PARSIFAL是一项II期随机临床试验，评估一线帕博西尼联合氟维司汀或来曲唑治疗HR[+]/HER2[-] ABC。没有发现明确的生物标志物，然而，CDK6阳性（p = 0.008）、ER阴性（p = 0.008）、高Ki67 （p = 0.04）和TP53突变（p = 0.04）的预后较差。耐药患者基线ctDNA密度（p = 0.036）和突变数（p = 0.033）显著高于耐药患者。我们的研究揭示了未来的探索方向，以确定对CDK4/6i反应的生物标志物。

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来源期刊

NPJ Breast Cancer Medicine-Pharmacology (medical)

CiteScore

10.10

自引率

1.70%

发文量

122

审稿时长

9 weeks

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.