Moukas Stefanos Ioannis, Dohn Merle, Lehnerdt Catrin, Welt Anja, Kolberg Hans-Christian, Hoffmann Oliver, Kimmig Rainer, Kasimir-Bauer Sabine, Keup Corinna
Department of Gynecology and Obstetrics, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
Department of Medical Oncology, University Hospital Essen, 45122, Essen, Germany.
Sci Rep. 2025 Mar 25;15(1):10347. doi: 10.1038/s41598-025-95114-7.
We investigated whether TK1 concentration or activity in the blood, drawn at baseline and under therapy, might have value for therapy management in 110 hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (mBC) patients treated with CDK4/6 inhibitors (CDK4/6i) and/or endocrine therapy (ET). TK1 concentration and activity were not significantly correlated with each other in matched samples. In the CDK4/6i cohort at baseline, high TK1 concentration and activity were significantly associated with a decreased PFS and primary resistance. Longitudinal sampling revealed a higher variability of TK1 concentration under therapy compared to TK1 activity that was reduced during therapy. Elevated TK1 activity after six months of CDK4/6i and an increase in TK1 concentration from baseline to six months under CDK4/6i significantly correlated with a decreased PFS. These results indicate a possible value of TK1 concentration and activity before and during CDK4/6i for HR+/HER2- mBC patients to guide treatment that warrants further investigation.
我们调查了在接受细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）和/或内分泌治疗（ET）的110例激素受体阳性（HR+）、人表皮生长因子受体2阴性（HER2-）转移性乳腺癌（mBC）患者中，基线期及治疗期间采集的血液中胸苷激酶1（TK1）浓度或活性是否对治疗管理有价值。在配对样本中，TK1浓度和活性彼此之间无显著相关性。在基线期的CDK4/6i队列中，高TK1浓度和活性与无进展生存期（PFS）缩短及原发性耐药显著相关。纵向采样显示，与治疗期间降低的TK1活性相比，治疗期间TK1浓度的变异性更高。CDK4/6i治疗6个月后TK1活性升高以及在CDK4/6i治疗下从基线期到6个月TK1浓度增加与PFS缩短显著相关。这些结果表明，对于HR+/HER2- mBC患者，在CDK4/6i治疗之前及期间，TK1浓度和活性可能对指导治疗有价值，值得进一步研究。
