Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Dynamics of Serum Thymidine Kinase 1 at the First Cycle of Neoadjuvant Chemotherapy Predicts Outcome of Disease in Estrogen-receptor-positive Breast Cancer

Version 1 : Received: 7 September 2021 / Approved: 8 September 2021 / Online: 8 September 2021 (16:25:39 CEST)

How to cite: Tribukait, B. Dynamics of Serum Thymidine Kinase 1 at the First Cycle of Neoadjuvant Chemotherapy Predicts Outcome of Disease in Estrogen-receptor-positive Breast Cancer. Preprints 2021, 2021090156 (doi: 10.20944/preprints202109.0156.v1). Tribukait, B. Dynamics of Serum Thymidine Kinase 1 at the First Cycle of Neoadjuvant Chemotherapy Predicts Outcome of Disease in Estrogen-receptor-positive Breast Cancer. Preprints 2021, 2021090156 (doi: 10.20944/preprints202109.0156.v1).

Abstract

Complete pathologic response (pCR) predicts the long-term outcome of neoadjuvant treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers able to guide adjustment or interruption of an ineffective therapy are desired. Here, we evaluated whether shifts in the serum concentration of thymidine kinase 1 (sTK1) during NAC could be utilized as a biomarker. In the PROMIX trial, women with localized HER2- BC received neoadjuvant epirubicin/docetaxel in six cycles. sTK1 was measured with an ELISA in 54 patients at cycles 1-4 and in a total of 131 patients before and 48h after cycle 1. The prognostic significance of the results was evaluated by log-rank tests of Kaplan–Meier estimates. Treatment resulted in a 2-fold increase of sTK1 before and 3-fold increase 48h after the cycles, except for the first cycle, where half of patients reacted with a decrease (post/pre sTK1- ratio <1.12) and the other half reacted with an increase (ratio >1.12). OS rates in ER+ patients with ratios of >1.12 and <1.12 were 97.7% and 78% (p=0.005), respectively, and DFS rates were 90.7% and 68% (p=0.006), respectively. Thus, response of sTK1 at the first cycle of chemotherapy could be used both as an early biomarker for guidance of chemotherapy and for the study of inherent tumor chemo-sensitivity, which could predict long-term outcome prior to therapy.

Keywords

circulating thymidine kinase 1; cell loss; biomarker; early treatment response; breast cancer

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