Breast Cancer Research and Treatment

, Volume 139, Issue 3, pp 751–758 | Cite as

Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial

  • J. Bjöhle
  • J. Bergqvist
  • J. S. Gronowitz
  • H. Johansson
  • L. Carlsson
  • Z. Einbeigi
  • B. Linderholm
  • N. Loman
  • M. Malmberg
  • M. Söderberg
  • M. Sundquist
  • T. M. Walz
  • M. Fernö
  • J. Bergh
  • T. Hatschek
Clinical Trial


The primary objective was to estimate serum thymidine kinase 1 (TK1) activity, reflecting total body cell proliferation rate including cancer cell proliferation, in women with loco regional inoperable or metastatic breast cancer participating in a prospective and randomized study. Secondary objectives were to analyze TK1 in relation to progression-free survival (PFS), overall survival (OS), therapy response and other tumour characteristics, including CA 15-3, widely used as a standard serum marker for disease progression. TK1 and CA 15-3 were analysed in 198 serum samples collected prospectively from women included in the randomized TEX trial between December 2002 and June 2007. TK1 activity was determined by the ELISA based DiviTum™ assay, and CA 15-3 analyses was generated with the electrochemiluminescence immunoassay Cobas Elecsys CA 15-3 II. High pre-treatment TK1 activity predicted shorter PFS (10 vs. 15 months p = 0.02) and OS (21 vs. 38 months, p < 0.0001), respectively. After adjustment for age, metastatic site and study treatment TK1 showed a trend as predictor of PFS (p = 0.059) and was an independent prognostic factor for OS, (HR 1.81, 95 % confidence interval (CI) 1.26–2.61, p = 0.001). There was a trend of shortened OS for women with high CA 15-3 (p = 0.054) in univariate analysis, but not after adjustment for the above mentioned covariates. Both TK1 (p = 0.0011) and CA 15-3 (p = 0.0004) predicted response to treatment. There were statistically different distributions of TK1 and CA 15-3 in relation to the site of metastases. TK1 activity measured by DiviTum™ predicted therapy response, PFS and OS in loco regional inoperable or disseminated breast cancer. These results suggest that this factor is a useful serum marker. In the present material, a prognostic value of CA 15-3 could not be proven.


TK1 CA 15-3 Breast cancer Prognostic factor Predictive factor DiviTum 



This study was supported by grants from the Swedish Cancer Society, Stockholm Cancer Society, King Gustav V Jubilee Fund, Swedish Research Council, Stockholm City Council, Karolinska Institutet and Stockholm County Council Research Strategy Committee, BRECT, Swedish Breast Cancer Association, Märit and Hans Rausing’s Initiative Against Breast Cancer, Karolinska Institutet Research Funds and Biovica International AB.

Conflict of interest

J Bergqvist has a family member who works as a consultant for Biovica International AB. S Gronowitz is employed by Biovica International AB and has family members who own shares in Biovica International AB.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • J. Bjöhle
    • 1
  • J. Bergqvist
    • 2
  • J. S. Gronowitz
    • 3
    • 4
  • H. Johansson
    • 1
  • L. Carlsson
    • 5
  • Z. Einbeigi
    • 6
  • B. Linderholm
    • 6
    • 7
  • N. Loman
    • 8
  • M. Malmberg
    • 9
  • M. Söderberg
    • 8
  • M. Sundquist
    • 10
  • T. M. Walz
    • 1
    • 11
  • M. Fernö
    • 8
  • J. Bergh
    • 1
  • T. Hatschek
    • 1
  1. 1.Department of OncologyKarolinska Institutet and University HospitalStockholmSweden
  2. 2.Karolinska Institutet and ASIH Långbro ParkStockholmSweden
  3. 3.Biovica International ABUppsalaSweden
  4. 4.Department of Medical SciencesUppsala UniversityUppsalaSweden
  5. 5.Department of OncologySundsvall General HospitalSundsvallSweden
  6. 6.Department of OncologySahlgrenska University HospitalGöteborgSweden
  7. 7.Cancer Center KarolinskaKarolinska InstitutetStockholmSweden
  8. 8.Division of Oncology, Department of Clinical SciencesLund UniversityLundSweden
  9. 9.Department of OncologyHelsingborg General HospitalHelsingborgSweden
  10. 10.Department of SurgeryKalmar General HospitalKalmarSweden
  11. 11.Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health SciencesLinköping UniversityLinköpingSweden

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