The Role of Serum Thymidine Kinase 1 Activity in Neoadjuvant-treated HER2-positive Breast Cancer: Biomarker Analysis from the Swedish Phase II Randomized PREDIX HER2 Trial

Overview

Journal Breast Cancer Res Treat

Specialty Oncology

Date 2024 Jan 4

PMID 38175448

Authors

Yajing Zhu

Ioannis Zerdes

Alexios Matikas

Ivette Raices Cruz

Mattias Bergqvist

Ellinor Elinder

Ana Bosch

Henrik Lindman

Zakaria Einbeigi

Anne Andersson

Lena Carlsson

Ann Charlotte Dreifaldt

Erika Isaksson-Friman

Mats Hellstrom

Hemming Johansson

Kang Wang

Jonas C S Bergh

Thomas Hatschek

Theodoros Foukakis

Affiliations

Soon will be listed here.

Abstract

Background: Thymidine kinase 1 (TK1) plays a pivotal role in DNA synthesis and cellular proliferation. TK1 has been studied as a prognostic marker and as an early indicator of treatment response in human epidermal growth factor 2 (HER2)-negative early and metastatic breast cancer (BC). However, the prognostic and predictive value of serial TK1 activity in HER2-positive BC remains unknown.

Methods: In the PREDIX HER2 trial, 197 HER2-positive BC patients were randomized to neoadjuvant trastuzumab, pertuzumab, and docetaxel (DPH) or trastuzumab emtansine (T-DM1), followed by surgery and adjuvant epirubicin and cyclophosphamide. Serum samples were prospectively collected from all participants at multiple timepoints: at baseline, after cycle 1, 2, 4, and 6, at end of adjuvant therapy, annually for a total period of 5 years and/or at the time of recurrence. The associations of sTK1 activity with baseline characteristics, pathologic complete response (pCR), event-free survival (EFS), and disease-free survival (DFS) were evaluated.

Results: No association was detected between baseline sTK1 levels and all the baseline clinicopathologic characteristics. An increase of TK1 activity from baseline to cycle 2 was seen in all cases. sTK1 level at baseline, after 2 and 4 cycles was not associated with pCR status. After a median follow-up of 58 months, 23 patients had EFS events. There was no significant effect between baseline or cycle 2 sTK1 activity and time to event. A non-significant trend was noted among patents with residual disease (non-pCR) and high sTK1 activity at the end of treatment visit, indicating a potentially worse long-term prognosis.

Conclusion: sTK1 activity increased following neoadjuvant therapy for HER2-positive BC but was not associated with patient outcomes or treatment benefit. However, the post-surgery prognostic value in patients that have not attained pCR warrants further investigation.

Trial Registration: ClinicalTrials.gov, NCT02568839. Registered on 6 October 2015.

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