Image: Diagram of DiviTum sTK1 assay: BrdUTP is subsequently incorporated into a solid-phase DNA-strand. Incorporated BrdU is detected using an anti-BrdU monoclonal antibody conjugated to the signal generating enzyme alkaline phosphatase. The level of BrdU incorporated over time is proportional to the level of thymidine kinase activity in the sample (Photo courtesy of Biovica).
Although prognosis and treatment of metastatic breast cancer (MBC) have improved over the last years, there is still an unmet clinical need for more precise prognostic and treatment monitoring tools.
Thymidine kinase 1 (TK1) is an enzyme involved in nucleotide metabolism and has a fundamental role in the DNA synthesis. It can be used as a marker of cell proliferation rate and the TK1 activity has demonstrated correlations to prognosis and usefulness for treatment monitoring in different malignancies.
A team of scientists working with those at Lund University (Lund, Sweden) studied 142 women with MBC scheduled for 1st line systemic treatment and included in a prospective monitoring trial who were evaluated for serum thymidine kinase 1 (sTK1) at baseline (BL) and during treatment at 1, 3 and 6 months. There were 132 patients who had at least one follow-up sample. sTK1 activity levels were measured and correlations to important clinic-pathological variables and prognosis. Progression-free survival (PFS) and overall survival (OS) at BL and during treatment were evaluated.
The investigators measured serum TK1 activity (sTK1) levels with the DiviTum assay. The median sTK1 level at BL was 391 u/L (range 10-35,520 u/L). When comparing patients with high (above median) versus low (below median) sTK1 levels at BL, high sTK1 levels were found to be associated to worse performance status and high number of metastatic sites. There was also a statistically significant association between high sTK1 levels and high Ki67 expression in biopsies from metastatic lesions. High sTK1 levels correlated to worse PFS and OS at BL. At diagnosis in the study, low DiviTum values correlated significantly and independently with improved progression free- and overall survival.
The authors concluded sTK1 activity level is an independent prognostic factor for PFS and OS in patients with MBC scheduled for 1st line systemic therapy. During treatment, sTK1 is prognostic for OS evaluated from all time-points up to six months. The sTK1 effects observed for PFS are slightly weaker, but still propose potential usefulness for treatment monitoring.
Lisa Rydén, MD, PhD, a professor in the department of surgery, said, “The results demonstrate that already after just one month of treatment, DiviTum is a highly valuable marker for clinical use regarding accurate prognosis. Throughout the course of therapy DiviTum can provide clinical information for patients with metastatic breast cancer scheduled for 1st line systemic therapy.” The study will be presented at the San Antonio Breast Cancer Symposium to be held December 5-9, 2017, in San Antonio, TX, USA.