Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial
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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.
KeywordsTK1 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.
- 7.Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, Parker JS, Luo J, DeSchryver K, Allred DC et al (2011) Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype–ACOSOG Z1031. J Clin Oncol 29(17):2342–2349PubMedCrossRefGoogle Scholar
- 15.Gronowitz JS, Bergstrom R, Nou E, Pahlman S, Brodin O, Nilsson S, Kallander CF (1990) Clinical and serologic markers of stage and prognosis in small cell lung cancer. A multivariate analysis. Cancer 66(4):722–732Google Scholar
- 21.Hatschek T, Carlsson L, Einbeigi Z, Lidbrink E, Linderholm B, Lindh B, Loman N, Malmberg M, Rotstein S, Soderberg M et al (2012) Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial. Breast Cancer Res Treat 131(3):939–947PubMedCrossRefGoogle Scholar
- 22.Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216PubMedCrossRefGoogle Scholar
- 23.WHO (1979) WHO Handbook for reporting results of treatment, 48th edn. World Health Organization, GenevaGoogle Scholar
- 25.Romain S, Spyratos F, Descotes F, Daver A, Rostaing-Puissant B, Bougnoux P, Colonna M, Bolla M, Martin PM (2000) Prognostic of DNA-synthesizing enzyme activities (thymidine kinase and thymidylate synthase) in 908 T1–T2, N0–N1, M0 breast cancers: a retrospective multicenter study. Int J Cancer 87(6):860–868PubMedCrossRefGoogle Scholar
- 29.Gronowitz JS (1984) Extracellular expression of TK isozymes in human body fluids, with special reference to herpesvirus diagnostics and use for monitoring of antiviral therapy. In: Sanna A, Morace G (eds.) New Horizons in Microbiology. Amsterdam, Elsevier Science Publishers, p. 273–284Google Scholar
- 33.Luporsi E, Andre F, Spyratos F, Martin PM, Jacquemier J, Penault-Llorca F, Tubiana-Mathieu N, Sigal-Zafrani B, Arnould L, Gompel A et al (2012) Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review. Breast Cancer Res Treat 132(3):895–915PubMedCrossRefGoogle Scholar