Thymidine kinase 1 concentration and activity in metastatic breast cancer under CDK4/6 inhibitor therapy

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.