Abstract
The rapid development of new therapies in metastatic breast cancer (MBC), entails a need for improved prognostic and monitoring tools. Thymidine kinase 1 (TK1) is involved in DNA synthesis and its activity correlates to outcome in cancer patients. The aim of this study was to evaluate serum TK1 activity (sTK1) levels in MBC patients as a tool for prognostication and treatment monitoring. 142 women with MBC scheduled for 1st line systemic treatment were included in a prospective observational study. sTK1 was measured at baseline (BL) and at 1, 3 and 6 months and correlations to progression-free and overall survival (PFS, OS) evaluated. High sTK1 levels (above median) correlated to worse PFS and OS at BL, also after adjusting for other prognostic factors. sTK1 levels were significantly associated with PFS and OS measured from follow-up time points during therapy. Changes from 3 to 6 months during therapy significantly correlated to PFS and OS, whereas early changes did not. We could demonstrate sTK1 level as an independent prognostic factor in patients with newly diagnosed MBC. Changes in sTK1 levels from 3 to 6 months correlated to PFS and OS. Future studies of sTK1 are warranted to further define its clinical utility.
Highlights
The rapid development of new therapies in metastatic breast cancer (MBC), entails a need for improved prognostic and monitoring tools
This study aims to evaluate serum TK1 activity (sTK1) levels in women with MBC scheduled for 1st line systemic therapy (ET, ChT or HER2 targeted therapy), at BL and by serial sampling during therapy, to further investigate the potential role of sTK1 in prognostication and therapy monitoring of MBC
We found that high sTK1 levels correlated significantly to worse performance status, high number of metastatic loci (≥3) and type of therapy (ChT and HER2-directed therapy)
Summary
The rapid development of new therapies in metastatic breast cancer (MBC), entails a need for improved prognostic and monitoring tools. The aim of this study was to evaluate serum TK1 activity (sTK1) levels in MBC patients as a tool for prognostication and treatment monitoring. Serum TK1 activity (sTK1) level has been proposed as a prognostic marker in MBC patients during endocrine therapy (ET) and as an indicator for early response in these patients[16,17]. It has been suggested as a marker for therapy response in cyclin-dependent kinase 4/6 inhibition (CDK-I) in patients with early breast cancer treated with neoadjuvant palbociclib[18]. Little is known about the potential prognostic role of sTK1 levels during systemic therapy in patients with newly diagnosed MBC, previously untreated for metastatic disease. This study aims to evaluate sTK1 levels in women with MBC scheduled for 1st line systemic therapy (ET, ChT or HER2 targeted therapy), at BL and by serial sampling during therapy, to further investigate the potential role of sTK1 in prognostication and therapy monitoring of MBC
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