Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer

Alexios Matikas ,K Wang,Samuel Rotstein ,Ariel Saracco ,Niklas Loman ,Mattias Bergqvist ,Tobias Lekberg ,Ioannis Zerdes ,Zakaria Einbeigi ,Balázs Ács ,Thomas Hatschek ,Anna Von Wachenfeldt ,Eleni Lagoudaki ,Judith Bjöhle ,Johan Hartman ,Lena Carlsson ,Ingrid Hedenfalk ,Jonas Bergh ,Edward Azavedo ,Mats Hellström ,Theodoros Foukakis

doi:10.1016/j.esmoop.2021.100076

Abstract

BackgroundEmerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate.MethodsMaterial from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models.ResultsCentral Ki67 counting had excellent correlation with the results of digital image analysis (r = 0.814), but not with the diagnostic samples (r = 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P = 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj = 0.50, 95% CI 0.26-0.97, P = 0.04) and OS (HRadj = 0.46, 95% CI 0.95, P = 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (pinteraction 0.04).ConclusionSerial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies.

Highlights

Following the demonstration that further adjuvant therapy improves survival in case of residual invasive breast cancer (BC) after neoadjuvant chemotherapy (NACT),[1,2] the latter is increasingly becoming the standard of care for the treatment of early BC.[3]
0.44-4.75), when adjusted for tumor size, nodal status and stratified for estrogen receptor (ER) status. In this correlative analysis of a prospective non-randomized trial, we aimed to evaluate the prognostic value of the longitudinal assessment of thymidine kinase 1 (TK1) activity as measured in serial blood samples
This study is the continuation of another correlative analysis using material from the same phase II trial where we demonstrated that the longitudinal assessment of immune function provides useful predictive information, and we emphasized the role of the immune microenvironment as a driver of chemosensitivity.[9]

Summary

Introduction

Following the demonstration that further adjuvant therapy improves survival in case of residual invasive breast cancer (BC) after neoadjuvant chemotherapy (NACT),[1,2] the latter is increasingly becoming the standard of care for the treatment of early BC.[3]. Volume 6 - Issue 2 - 2021 progression is a priority To this end, clinical response,[4,5] positron emission tomography,[6,7] tumor infiltrating lymphocytes[8] and immune function genes[9] have been explored as predictors of both short- and long-term outcomes. Clinical response,[4,5] positron emission tomography,[6,7] tumor infiltrating lymphocytes[8] and immune function genes[9] have been explored as predictors of both short- and long-term outcomes

Objectives

Methods

Results

Conclusion