Thymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226). (3rd April 2023)

• Record Type: Journal Article
• Authors: Bergqvist, Mattias; Nordmark, Adrian; Williams, Amy; Paoletti, Costanza; Barlow, William; Cobain, Erin F.; Mehta, Rita S.; Gralow, Julie R.; Hortobagyi, Gabriel N.; Albain, Kathy S.; Pusztai, Lajos; Sharma, Priyanka; Godwin, Andrew K.; Thompson, Alastair M.; Hayes, Daniel F.; Rae, James M.
• Is Part Of: Biomarkers. Volume 28:Number 3(2023)
• Page Start: 313
• Page End: 322
• Publication Date: 2023-04-03
• Subjects: Thymidine kinase -- biomarker -- disease progression -- monitoring treatment -- breast cancer -- endocrine therapy; Biochemical markers -- Periodicals; 610.28
• DOI: 10.1080/1354750X.2023.2168063
• Languages: English
• ISSNs: 1354-750X

Abstract

Abstract: Background: Some patients with metastatic breast cancer (MBC) stay on endocrine therapy (ET) for years and others progress quickly. Serum thymidine kinase activity (TKa), an indicator of cell-proliferation, is a potential biomarker for monitoring ET and predicting MBC outcome. We have previously reported TKa as being prognostic in MBC in SWOG S0226. Here, new data on progression within 30/60 days post sampling, with a new, FDA approved version of DiviTum ® TKa highlighting differences vs. a Research Use Only version is reported. Methods: 1, 546 serum samples from 454 patients were assessed, collected at baseline and at 4 subsequent timepoints during treatment. A new predefined cut-off tested the ability to predict disease progression. A new measuring unit, DuA (DiviTum ® unit of Activity) is adopted. Results: A DiviTum ® TKa score <250 DuA provides a much lower risk of progression within 30/60 days after blood draw, the negative predictive value (NPV) was 96.7% and 93.5%, respectively. Patients <250 DuA experienced significantly longer progression-free survival and overall survival, demonstrated at baseline and for all time intervals. Conclusions: DiviTum ® TKa provides clinically meaningful information for patients with HR+ MBC. Low TKa levels provide such a high NPV for rapid progression that such patients might forego additional therapy added to single agent ET. Trial registration: NCT00075764