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

Abstract

Pathologic complete response (pCR) predicts the long-term outcome of neoadjuvantly treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers enabling adjustment or interruption of an ineffective therapy are desired. Here, we evaluated whether changes 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 an additional 77 patients before and 48 h after treatment 1. Treatment resulted in a 2-fold increase of sTK1 before and a 3-fold increase 48 h after the cycles, except for the first cycle, where half of the patients reacted with a significant decrease and the other half with an increase of sTK1. In Kaplan–Meier estimates of ER+ patients divided by the median of the post/pre-treatment sTK1 ratio at the first treatment cycle, OS was 97.7% and 78% (p = 0.005), and DFS was 90.7% and 68% (p = 0.006), respectively. Thus, the response of sTK1 at the first cycle of chemotherapy could be used both as an early biomarker for the guidance of chemotherapy and for the study of inherent tumor chemo-sensitivity, which could predict long-term outcome prior to therapy.