Plasma thymidine kinase-1 activity predicts outcome in patients with hormone receptor positive and HER2 negative metastatic breast cancer treated with endocrine therapy

// Martina Bonechi 1, * , Francesca Galardi 1, * , Chiara Biagioni 2 , Francesca De Luca 1 , Mattias Bergqvist 3 , Magnus Neumüller 3 , Cristina Guarducci 1 , Giulia Boccalini 1 , Stefano Gabellini 1 , Ilenia Migliaccio 1 , Angelo Di Leo 1, 4 , Marta Pestrin 1, 4, ** and Luca Malorni 1, 4, ** 1 “Sandro Pitigliani” Translational Research Unit, Hospital of Prato, Prato, Italy 2 Bioinformatics Unit, Hospital of Prato, Prato, Italy 3 Biovica International, Uppsala Science Park, Uppsala, Sweden 4 “Sandro Pitigliani” Medical Oncology Department, Hospital of Prato, Prato, Italy * Co-first authors ** Co-last authors Correspondence to: Luca Malorni, email: luca.malorni@uslcentro.toscana.it Keywords: metastatic breast cancer; endocrine therapy; thymidine kinase-1; liquid biopsy; circulating biomarkers Received: October 15, 2017 Accepted: February 28, 2018 Published: March 27, 2018 ABSTRACT The aim of this study was to investigate if thymidine kinase-1 (TK1), a well-known proliferation marker, could represent a valid circulating biomarker to identify hormone receptor positive (HR+)/HER2 negative (HER2neg) metastatic breast cancer (MBC) patients most likely to benefit from endocrine therapy (ET). We used the DiviTum TM assay to analyze TK1 activity in cell lysates of three HR+/HER2neg BC cell lines and in plasma of 31 HR+/HER2neg MBC patients receiving ET. Blood samples were collected at treatment initiation, after one month and at disease progression. CTCs count and ESR1 / PIK3CA mutations in circulating tumor DNA were performed and correlated with TK1 activity. TK1 activity was reduced in the two endocrine-sensitive cell lines after 2 days of treatment. In patients, high baseline TK1 activity correlated with CTCs positivity (p-value=0.014). Patients with low baseline levels of TK1 activity had a significantly better PFS compared to those with high baseline TK1 activity (p-value=0.012). Patients with an early drop of TK1 activity after one month of treatment had a significantly better PFS compared to those who experienced an increase (p-value=0.0026). Our study suggests that TK1 could be a potential prognostic, predictive and monitoring marker of early ET response in HR+/HER2neg MBC patients.