Evidence map›Paper›PMID 39423142›Full record

SynthesisJournal of the National Cancer Institute2025

Validation of a breast cancer assay for radiotherapy omission: an individual participant data meta-analysis.

Per Karlsson, Anthony Fyles, S Laura Chang, Bradley Arrick, Frederick L Baehner, Per Malmström, Mårtin Fernö, Erik Holmberg, Martin Sjöström, Fei-Fei Liu and 14 more

Abstract readMeta-AnalysisValidation Study
In one paragraph

Synthesis in Journal of the National Cancer Institute, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Endothelial Cell pY397-FAK Expression Predicts the Risk of Breast Cancer Recurrences after Radiotherapy in the SweBCG91-RT Cohort.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Trial
  2. 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

24 authors.

Per KarlssonDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.ORCID 0000-0003-4841-2672
Anthony FylesPrincess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-3633-2483
S Laura ChangExact Sciences Corporation, Madison, WI, United States.
Bradley ArrickExact Sciences Corporation, Madison, WI, United States.
Frederick L BaehnerExact Sciences Corporation, Madison, WI, United States.ORCID 0000-0001-6883-1212
Per MalmströmDivision of Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden.
Mårtin FernöDivision of Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden.ORCID 0000-0003-2220-1236
Erik HolmbergDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.ORCID 0000-0001-5107-4550
Martin SjöströmDivision of Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden.ORCID 0000-0002-2629-9966
Fei-Fei LiuPrincess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.ORCID 0000-0003-4344-6486
David A CameronCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0002-2717-7979
Linda J WilliamsUsher Institute, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0002-6317-1718
John M S BartlettCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0002-0347-3888
Joanna DunlopPublic Health Scotland, Edinburgh, United Kingdom.ORCID 0000-0001-5019-6118
Jacqueline CaldwellPublic Health Scotland, Edinburgh, United Kingdom.ORCID 0000-0002-3506-2936
Joseph F LoaneQueen Elizabeth University Hospital, Glasgow, Scotland.
Elizabeth MallonQueen Elizabeth University Hospital, Glasgow, Scotland.ORCID 0009-0009-3423-4220
Tammy PiperCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Ian KunklerCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
Felix Y FengDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, United States.ORCID 0000-0001-9756-4037
Corey W SpeersDepartment of Radiation Oncology, Case Comprehensive Cancer Center, OH, United States.ORCID 0000-0002-2362-2860
Lori J PierceDepartment of Radiation Oncology, Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, United States.ORCID 0000-0002-3734-5710
John P BennettExact Sciences Corporation, Madison, WI, United States.ORCID 0000-0001-5184-7912
Karen J TaylorCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0002-2265-5097

Funding

Breast Cancer Institute FundCIHREdinburgh and Lothian Health FoundationExact Sciences CorporationPFS GenomicsSwedish Cancer SocietySwedish Research Council
6 · The paper itself

Abstract

backgroundThere are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low-risk cancers where RT will not further reduce recurrence rates.

methodsAn individual participant data meta-analysis was performed in 623 patients of node-negative estrogen receptor-positive and HER2-negative early breast cancer enrolled in 3 RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence was used to test the interaction between POLAR score and RT.

resultsA total of 429 (69%) patients' tumors had a high POLAR score, and 194 (31%) had a low score. Patients with high POLAR score had, in the absence of RT, a 10-year cumulative incidence of locoregional recurrence (20%, 95% confidence interval [CI] = 15% to 26%, vs 5%, [CI] 2% to 11%) for those with a low score. Patients with a high POLAR score had a large benefit from RT (hazard ratio [HR] for RT vs no RT = 0.37, 95% CI = 0.23 to 0.60; P < .001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR = 0.92, 95% CI = 0.42 to 2.02; P = .832). The test for interaction between RT and POLAR was statistically significant (P = .022).

conclusionsPOLAR is not only prognostic for locoregional recurrence but also predictive of benefit from RT in selected patients. Patients aged 50 years and older with estrogen receptor-positive and HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required.

Indexed as

Biomarkers, TumorBreast NeoplasmsNeoplasm Recurrence, LocalAdultAgedErb-b2 Receptor Tyrosine KinasesFemaleGene Expression ProfilingHumansMiddle AgedProportional Hazards ModelsRadiotherapy, AdjuvantRandomized Controlled Trials as TopicReceptors, EstrogenBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesReceptors, Estrogen

Identifiers

PMID39423142
PMCPMC11884857

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.