Evidence map›Paper›PMID 41670750›Full record

Observational studyBreast cancer research and treatment2026

Prognostic performance of thymidine kinase 1 activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with CDK4/6 and aromatase inhibitors.

Nicole L Brown, Sacha J Howell, Dimitrios Papantoniou, Olle Eriksson, Mattias Bergqvist, Amy Williams, Amy Kavanagh, Alexandra Backlund, Ahmed Albu-Kareem, Ellinor Elinder and 3 more

Abstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Breast cancer research and treatment, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Nicole L BrownThe Christie NHS Foundation Trust, Manchester, M20 4BX, UK.
Sacha J HowellThe Christie NHS Foundation Trust, Manchester, M20 4BX, UK.
Dimitrios PapantoniouRyhov County Hospital, Department of Oncology, SE-551 85, Jönköping, Sweden.
Olle ErikssonFuturum - The Academy for Health and Care, SE-551 85, Jönköping, Region Jönköping County, Sweden.
Mattias BergqvistBiovica International AB, SE-752 37, Uppsala, Sweden.
Amy WilliamsBiovica International AB, SE-752 37, Uppsala, Sweden.
Amy KavanaghThe Christie NHS Foundation Trust, Manchester, M20 4BX, UK.
Alexandra BacklundRyhov County Hospital, Department of Oncology, SE-551 85, Jönköping, Sweden.
Ahmed Albu-KareemLinköping University Hospital, Department of Oncology, SE-581 85, Linköping, Sweden.
Ellinor ElinderSödersjukhuset, Department of Oncology, SE-118 83, Stockholm, Sweden.
Karolina LarssonDepartment of Oncology, Sahlgrenska University Hospital, SE-413 45, Gothenburg, Sweden.
Monika UminskaKalmar County Hospital, Department of Oncology, SE-391 85, Kalmar, Sweden.
Maria EkholmRyhov County Hospital, Department of Oncology, SE-551 85, Jönköping, Sweden. maria.ekholm@liu.se.ORCID http://orcid.org/0000-0002-5553-5323

Funding

ALF grants from Region Östergötland RÖ-1013092Cancerfonden 23 2760 FkForskningsrådet i Sydöstra Sverige FORSS-989664, FORSS-995301Foundation for Clinical Cancer Research in Jönköping 180424-2, 20201116-1Futurum - Akademin för Hälsa och Vård, Region Jönköpings läns FUTURUM- 989624Percy Falk Foundation 2018, 2019Svenska Läkaresällskapet SLS-874931Swedish Breast Cancer Association F2018-03, F2019-005The Christie Charity charity number 1201654
6 · The paper itself

Abstract

purposeThymidine kinase 1 activity (TKa) has previously been demonstrated as a prognostic biomarker for progression-free survival (PFS) in hormone receptor-positive, HER2-negative metastatic breast cancer (MBC), but its optimal use remains undefined. This study evaluated the prognostic performance of TKa across multiple sampling time points and thresholds in patients receiving first-line CDK4/6 inhibitor plus aromatase inhibitor therapy.

methodsTKa was measured (DiviTum® assay) at baseline (BL), cycle 1 day 15 (C1D15), and cycle 2 day 1 (C2D1) in patients enrolled in the PDM-MBC study (n = 90). Thresholds for PFS discrimination were identified using maximally selected rank statistics, with predefined cut-offs tested for comparison. Prognostic performance was assessed using the corrected Akaike information criterion (AICc) and Harrell's concordance index (C-index).

resultsTKa was prognostic at all time points. Data-derived thresholds identified groups with differing PFS and overall survival (OS), and predefined cut-offs (≥ 50, ≥ 100, ≥ 250 DiviTum® units of Activity [DuA]) also discriminated survival outcomes. BL and C2D1 models performed better than C1D15 and comparably to multi-time-point models. Among patients with BL TKa ≥ 250 DuA, suppression to < 100 DuA at C1D15 was associated with longer median PFS (23.9 vs. 10.3 months; p = 0.034).

conclusionBaseline TKa provides prognostic information, with potential added value from repeated testing in those with high baseline levels. TKa behaves as a continuous biomarker of risk, and continuous modelling may offer more clinically informative individual risk estimation, while thresholds may retain value for specific clinical contexts. Validation in larger cohorts is warranted to support integration into routine practice.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsAromatase InhibitorsBiomarkers, TumorBreast NeoplasmsCyclin-Dependent Kinase Inhibitor ProteinsThymidine KinaseAgedArea Under CurveCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Erb-b2 Receptor Tyrosine KinasesFemaleHumansMaleMiddle AgedNeoplasm MetastasisAromatase InhibitorsBiomarkers, TumorCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Cyclin-Dependent Kinase Inhibitor ProteinsERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesReceptors, EstrogenReceptors, ProgesteroneThymidine Kinasethymidine kinase 1Advanced breast cancerAromatase inhibitorsCDK4/6 inhibitorsPrognostic biomarkerSurvival analysisThymidine kinase 1

Identifiers

PMID41670750
PMCPMC12894156

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.