The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer: biomarker analysis from the Swedish phase II randomized PREDIX HER2 trial

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The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer : biomarker analysis from the Swedish phase II randomized PREDIX HER2 trial

Zhu, Yajing (författare): Karolinska Institutet,Karolinska Inst, Dept Oncol Pathol, Karolinska Vagen A2-07, S-17164 Stockholm, Sweden.

Zerdes, Ioannis (författare): Karolinska Institutet,Karolinska Inst, Dept Oncol Pathol, Karolinska Vagen A2-07, S-17164 Stockholm, Sweden.;Karolinska Univ Hosp, Breast Ctr, Theme Canc, Stockholm, Sweden.

Matikas, Alexios (författare): Karolinska Institutet,Karolinska Inst, Dept Oncol Pathol, Karolinska Vagen A2-07, S-17164 Stockholm, Sweden.;Karolinska Univ Hosp, Breast Ctr, Theme Canc, Stockholm, Sweden.

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Cruz, Ivette Raices (författare): Karolinska Inst, Inst Environm Med, Div Biostat, Stockholm, Sweden.,Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Bergqvist, Mattias (författare): Biov Int, Uppsala Sci Pk, Uppsala, Sweden.,Biovica International, Uppsala Science Park, Uppsala, Sweden

Elinder, Ellinor (författare): Soder Sjukhuset, Dept Oncol, Stockholm, Sweden.,Department of Oncology, South Hospital, Stockholm, Sweden

Bosch, Ana (författare): Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden.,Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden

Lindman, Henrik (författare): Uppsala Univ Hosp, Dept Oncol, Uppsala, Sweden.,Department of Oncology, Uppsala University Hospital, Uppsala, Sweden

Einbeigi, Zakaria (författare): Southern Alvsborg Hosp, Dept Oncol, Borås, Sweden.,Department of Oncology, Southern Älvsborg Hospital, Borås, Sweden

Andersson, Anne, 1966- (författare): Umeå universitet,Onkologi,Umeå Univ, Umeå, Sweden.

Carlsson, Lena (författare): Sundsvall Hosp, Dept Oncol, Sundsvall, Sweden.,Department of Oncology, Sundsvall Hospital, Sundsvall, Sweden

Dreifaldt, Ann Charlotte (författare): Örebro Univ Hosp, Dept Oncol, Örebro, Sweden.,Department of Oncology, Örebro University Hospital, Örebro, Sweden

Isaksson-Friman, Erika (författare): St Goran Hosp, Dept Oncol, Stockholm, Sweden.,Department of Oncology, St Göran Hospital, Stockholm, Sweden

Hellstrom, Mats (författare): Karolinska Univ Hosp, Ctr Clin Canc Studies, Theme Canc, Stockholm, Sweden.,Centre for Clinical Cancer Studies, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden

Johansson, Hemming (författare): Karolinska Institutet,Karolinska Univ Hosp, Ctr Clin Canc Studies, Theme Canc, Stockholm, Sweden.

Wang, Kang (författare): Karolinska Inst, Dept Oncol Pathol, Karolinska Vagen A2-07, S-17164 Stockholm, Sweden.,Department of Oncology-Pathology, Karolinska Institutet, Karolinska Vägen A2:07, Solna, Stockholm, Sweden

Bergh, Jonas C. S. (författare): Karolinska Institutet,Karolinska Inst, Dept Oncol Pathol, Karolinska Vagen A2-07, S-17164 Stockholm, Sweden.;Karolinska Univ Hosp, Breast Ctr, Theme Canc, Stockholm, Sweden.

Hatschek, Thomas (författare): Karolinska Inst, Dept Oncol Pathol, Karolinska Vagen A2-07, S-17164 Stockholm, Sweden.;Karolinska Univ Hosp, Breast Ctr, Theme Canc, Stockholm, Sweden.,Department of Oncology-Pathology, Karolinska Institutet, Karolinska Vägen A2:07, Solna, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden

Foukakis, Theodoros (författare): Karolinska Institutet,Karolinska Inst, Dept Oncol Pathol, Karolinska Vagen A2-07, S-17164 Stockholm, Sweden.;Karolinska Univ Hosp, Breast Ctr, Theme Canc, Stockholm, Sweden.

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Karolinska Institutet Karolinska Inst, Dept Oncol Pathol, Karolinska Vagen A2-07, S-17164 Stockholm, Sweden (creator_code:org_t)

Springer, 2024
2024
Engelska.
Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 204:2, s. 299-308

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://uu.diva-port... (primary) (Raw object); https://umu.diva-por... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; https://urn.kb.se/re...; http://kipublication...; visa färre...

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BackgroundThymidine kinase 1 (TK1) plays a pivotal role in DNA synthesis and cellular proliferation. TK1 has been studied as a prognostic marker and as an early indicator of treatment response in human epidermal growth factor 2 (HER2)-negative early and metastatic breast cancer (BC). However, the prognostic and predictive value of serial TK1 activity in HER2-positive BC remains unknown.MethodsIn the PREDIX HER2 trial, 197 HER2-positive BC patients were randomized to neoadjuvant trastuzumab, pertuzumab, and docetaxel (DPH) or trastuzumab emtansine (T-DM1), followed by surgery and adjuvant epirubicin and cyclophosphamide. Serum samples were prospectively collected from all participants at multiple timepoints: at baseline, after cycle 1, 2, 4, and 6, at end of adjuvant therapy, annually for a total period of 5 years and/or at the time of recurrence. The associations of sTK1 activity with baseline characteristics, pathologic complete response (pCR), event-free survival (EFS), and disease-free survival (DFS) were evaluated.ResultsNo association was detected between baseline sTK1 levels and all the baseline clinicopathologic characteristics. An increase of TK1 activity from baseline to cycle 2 was seen in all cases. sTK1 level at baseline, after 2 and 4 cycles was not associated with pCR status. After a median follow-up of 58 months, 23 patients had EFS events. There was no significant effect between baseline or cycle 2 sTK1 activity and time to event. A non-significant trend was noted among patents with residual disease (non-pCR) and high sTK1 activity at the end of treatment visit, indicating a potentially worse long-term prognosis.ConclusionsTK1 activity increased following neoadjuvant therapy for HER2-positive BC but was not associated with patient outcomes or treatment benefit. However, the post-surgery prognostic value in patients that have not attained pCR warrants further investigation.Trial registrationClinicalTrials.gov, NCT02568839. Registered on 6 October 2015.

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The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer : biomarker analysis from the Swedish phase II randomized PREDIX HER2 trial

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