Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer. 2021

A Matikas, and K Wang, and E Lagoudaki, and B Acs, and I Zerdes, and J Hartman, and E Azavedo, and J Bjöhle, and L Carlsson, and Z Einbeigi, and I Hedenfalk, and M Hellström, and T Lekberg, and N Loman, and A Saracco, and A von Wachenfeldt, and S Rotstein, and M Bergqvist, and J Bergh, and T Hatschek, and T Foukakis
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden. Electronic address: alexios.matikas@ki.se.

Emerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate. Material from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models. Central Ki67 counting had excellent correlation with the results of digital image analysis (r = 0.814), but not with the diagnostic samples (r = 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P = 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj = 0.50, 95% CI 0.26-0.97, P = 0.04) and OS (HRadj = 0.46, 95% CI 0.95, P = 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (pinteraction 0.04). Serial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013937 Thymidine Kinase An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. Deoxythymidine Kinase,Deoxypyrimidine Kinase,Kinase, Deoxypyrimidine,Kinase, Deoxythymidine,Kinase, Thymidine
D014408 Biomarkers, Tumor Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or BODY FLUIDS. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including HORMONES; ANTIGENS; amino and NUCLEIC ACIDS; ENZYMES; POLYAMINES; and specific CELL MEMBRANE PROTEINS and LIPIDS. Biochemical Tumor Marker,Cancer Biomarker,Carcinogen Markers,Markers, Tumor,Metabolite Markers, Neoplasm,Tumor Biomarker,Tumor Marker,Tumor Markers, Biochemical,Tumor Markers, Biological,Biochemical Tumor Markers,Biological Tumor Marker,Biological Tumor Markers,Biomarkers, Cancer,Marker, Biochemical Tumor,Marker, Biologic Tumor,Marker, Biological Tumor,Marker, Neoplasm Metabolite,Marker, Tumor Metabolite,Markers, Biochemical Tumor,Markers, Biological Tumor,Markers, Neoplasm Metabolite,Markers, Tumor Metabolite,Metabolite Markers, Tumor,Neoplasm Metabolite Markers,Tumor Markers, Biologic,Tumor Metabolite Marker,Biologic Tumor Marker,Biologic Tumor Markers,Biomarker, Cancer,Biomarker, Tumor,Cancer Biomarkers,Marker, Tumor,Markers, Biologic Tumor,Markers, Carcinogen,Metabolite Marker, Neoplasm,Metabolite Marker, Tumor,Neoplasm Metabolite Marker,Tumor Biomarkers,Tumor Marker, Biochemical,Tumor Marker, Biologic,Tumor Marker, Biological,Tumor Markers,Tumor Metabolite Markers
D020360 Neoadjuvant Therapy Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, IMMUNOTHERAPY, HYPERTHERMIA, INDUCED etc.) that is given before the main therapy. Neoadjuvant Chemoradiation,Neoadjuvant Chemoradiation Therapy,Neoadjuvant Chemoradiation Treatment,Neoadjuvant Chemoradiotherapy,Neoadjuvant Chemotherapy,Neoadjuvant Chemotherapy Treatment,Neoadjuvant Radiation,Neoadjuvant Radiation Therapy,Neoadjuvant Radiation Treatment,Neoadjuvant Radiotherapy,Neoadjuvant Systemic Therapy,Neoadjuvant Systemic Treatment,Neoadjuvant Treatment,Chemoradiation Therapy, Neoadjuvant,Chemoradiation Treatment, Neoadjuvant,Chemoradiation, Neoadjuvant,Chemoradiotherapy, Neoadjuvant,Chemotherapy Treatment, Neoadjuvant,Chemotherapy, Neoadjuvant,Neoadjuvant Chemoradiation Therapies,Neoadjuvant Chemoradiation Treatments,Neoadjuvant Chemoradiations,Neoadjuvant Chemoradiotherapies,Neoadjuvant Chemotherapies,Neoadjuvant Chemotherapy Treatments,Neoadjuvant Radiation Therapies,Neoadjuvant Radiation Treatments,Neoadjuvant Radiations,Neoadjuvant Radiotherapies,Neoadjuvant Systemic Therapies,Neoadjuvant Systemic Treatments,Neoadjuvant Therapies,Neoadjuvant Treatments,Radiation Therapy, Neoadjuvant,Radiation Treatment, Neoadjuvant,Radiation, Neoadjuvant,Radiotherapy, Neoadjuvant,Systemic Therapy, Neoadjuvant,Systemic Treatment, Neoadjuvant,Therapy, Neoadjuvant,Therapy, Neoadjuvant Chemoradiation,Therapy, Neoadjuvant Radiation,Therapy, Neoadjuvant Systemic,Treatment, Neoadjuvant,Treatment, Neoadjuvant Chemoradiation,Treatment, Neoadjuvant Chemotherapy,Treatment, Neoadjuvant Radiation,Treatment, Neoadjuvant Systemic

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