Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer
(2021) In ESMO Open 6(2).- Abstract
BACKGROUND: 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. METHODS: 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... (More)
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
(Less)
- author
- Matikas, A.
; Wang, K.
LU
; Lagoudaki, E.
; Acs, B.
; Zerdes, I.
; Hartman, J.
; Azavedo, E.
; Bjöhle, J.
; Carlsson, L.
; Einbeigi, Z.
; Hedenfalk, I.
LU
; Hellström, M.
; Lekberg, T.
; Loman, N.
LU
; Saracco, A.
; von Wachenfeldt, A.
; Rotstein, S.
; Bergqvist, M.
; Bergh, J.
; Hatschek, T.
and Foukakis, T.
(Less) - organization
- publishing date
- 2021-04-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- breast cancer, longitudinal, neoadjuvant chemotherapy, prognosis, thymidine kinase 1, TK1 kinetics
- in
- ESMO Open
- volume
- 6
- issue
- 2
- article number
- 100076
- publisher
- BMJ Publishing Group
- external identifiers
-
- scopus:85105896263
- pmid:33714010
- ISSN
- 2059-7029
- DOI
- 10.1016/j.esmoop.2021.100076
- language
- English
- LU publication?
- yes
- id
- a36b7b22-34c5-4b4b-b2ea-caf9611416a2
- date added to LUP
- 2021-06-01 10:50:09
- date last changed
- 2024-04-20 06:47:31
@article{a36b7b22-34c5-4b4b-b2ea-caf9611416a2,
abstract = {{<p>BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.</p>}},
author = {{Matikas, A. and Wang, K. and Lagoudaki, E. and Acs, B. and Zerdes, I. and Hartman, J. and Azavedo, E. and Bjöhle, J. and Carlsson, L. and Einbeigi, Z. and Hedenfalk, I. and Hellström, M. and Lekberg, T. and Loman, N. and Saracco, A. and von Wachenfeldt, A. and Rotstein, S. and Bergqvist, M. and Bergh, J. and Hatschek, T. and Foukakis, T.}},
issn = {{2059-7029}},
keywords = {{breast cancer; longitudinal; neoadjuvant chemotherapy; prognosis; thymidine kinase 1; TK1 kinetics}},
language = {{eng}},
month = {{04}},
number = {{2}},
publisher = {{BMJ Publishing Group}},
series = {{ESMO Open}},
title = {{Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer}},
url = {{http://dx.doi.org/10.1016/j.esmoop.2021.100076}},
doi = {{10.1016/j.esmoop.2021.100076}},
volume = {{6}},
year = {{2021}},
}