title: Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial.
abstract: 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.
authors.affiliation: Department of Oncology, Karolinska Institutet and University Hospital, Radiumhemmet, 171 76 Stockholm, Sweden. judith.bjohle@karolinska.se
authors.forename: J
authors.initials: J
authors.lastname: Bjöhle
authors.forename: J
authors.initials: J
authors.lastname: Bergqvist
authors.forename: J S
authors.initials: JS
authors.lastname: Gronowitz
authors.forename: H
authors.initials: H
authors.lastname: Johansson
authors.forename: L
authors.initials: L
authors.lastname: Carlsson
authors.forename: Z
authors.initials: Z
authors.lastname: Einbeigi
authors.forename: B
authors.initials: B
authors.lastname: Linderholm
authors.forename: N
authors.initials: N
authors.lastname: Loman
authors.forename: M
authors.initials: M
authors.lastname: Malmberg
authors.forename: M
authors.initials: M
authors.lastname: Söderberg
authors.forename: M
authors.initials: M
authors.lastname: Sundquist
authors.forename: T M
authors.initials: TM
authors.lastname: Walz
authors.forename: M
authors.initials: M
authors.lastname: Fernö
authors.forename: J
authors.initials: J
authors.lastname: Bergh
authors.forename: T
authors.initials: T
authors.lastname: Hatschek
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015996:Survival Rate; D013937:Thymidine Kinase / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D018396:Mucin-1; D013937:Thymidine Kinase; C092717:thymidine kinase 1