Albanell Joan, Pozo Angelo Gámez, Arteaga Carlos L, Bellet Meritxell, Rojo Federico, González Abel, Bellosillo Beatriz, Serra Violeta, Gener Petra, Guerrero José Antonio, Shimizu Eileen, Mancino Mario, Rodríguez-Morató Jose, Mina Leonardo, Pérez-García José Manuel, Cortés Javier, Llombart-Cussac Antonio
Hospital del Mar Research Institute Barcelona, Depatment of Medical Oncology, Hospital del Mar, Barcelona, Spain.
Universitat Pompeu Fabra, Barcelona, Spain.
NPJ Breast Cancer. 2025 Jun 20;11(1):59. doi: 10.1038/s41523-025-00777-0.
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.
目前，尚无临床上可用于预测激素受体（HR）阳性/人表皮生长因子受体2（HER2）阴性晚期乳腺癌（ABC）患者对细胞周期蛋白依赖性激酶4和6抑制剂（CDK4/6i）联合内分泌治疗反应的生物标志物。在此，我们报告了一项探索性生物标志物亚研究（transFAL），该研究来自PARSIFAL试验纳入的部分患者，PARSIFAL是一项II期随机临床试验，评估了一线哌柏西利联合氟维司群或来曲唑用于HR阳性/HER2阴性ABC的疗效。然而，未发现明确的生物标志物，但发现CDK6阳性（p = 0.008）、雌激素受体（ER）阴性（p = 0.008）、高Ki67（p = 0.04）和TP53突变（p = 0.04）的患者预后较差。基线时，耐药患者的循环肿瘤DNA（ctDNA）密度（p = 0.036）和突变数量（p = 0.033）显著更高。我们的研究揭示了未来探索的方向，目标是确定对CDK4/6i反应的生物标志物。
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