Evidence map›Paper›PMID 37208129›Full record

Trial reportJournal for immunotherapy of cancer2023

Combining histological grade, TILs, and the PD-1/PD-L1 pathway to identify immunogenic tumors and de-escalate radiotherapy in early breast cancer: a secondary analysis of a randomized clinical trial.

Axel Stenmark Tullberg, Martin Sjöström, Lena Tran, Emma Niméus, Fredrika Killander, Anikó Kovács, Dan Lundstedt, Erik Holmberg, Per Karlsson

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06637202 (SB), which is not on this map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
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.

NCT06637202 naactive not recruitingnot on this map

SB (Swedish Breast Cancer Group) 91:A Breast Conserving Surgery With or Without Postoperative Radiotherapy for Breast Cancer Stage 1-2 (<30 mm) pN0, M0

TypeinterventionalSponsorRegion SkaneRan1991 to 2025Enrolled1,187ConditionsBreast Cancer Early Stage Breast Cancer (Stage 1-3)Armspostoperative radiotherapy
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Trial
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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

9 authors at 4 institutions in 2 countries.

Axel Stenmark TullbergDepartment of Oncology, University of Gothenburg Institute of Clinical Sciences, Goteborg, Sweden axel.tullberg@gu.se.ORCID 0000-0002-3652-3706
Martin SjöströmDepartment of Radiation Oncology, UCSF, San Francisco, California, USA.
Lena TranDepartment of Clinical Sciences Lund, Oncology/Pathology and Surgery, Lund University, Lund, Sweden.
Emma NiméusDepartment of Clinical Sciences Lund, Oncology/Pathology and Surgery, Lund University, Lund, Sweden.
Fredrika KillanderDepartment of Clinical Sciences Lund, Oncology/Pathology and Surgery, Lund University, Lund, Sweden.
Anikó KovácsDepartment of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Dan LundstedtDepartment of Oncology, University of Gothenburg Institute of Clinical Sciences, Goteborg, Sweden.
Erik HolmbergDepartment of Oncology, University of Gothenburg Institute of Clinical Sciences, Goteborg, Sweden.
Per KarlssonDepartment of Oncology, University of Gothenburg Institute of Clinical Sciences, Goteborg, Sweden.ORCID 0000-0003-4841-2672
University of Gothenburg · SELund University · SESahlgrenska University Hospital · SEUniversity of California, San Francisco · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe implementation of immunological biomarkers for radiotherapy (RT) individualization in breast cancer requires consideration of tumor-intrinsic factors. This study aimed to investigate whether the integration of histological grade, tumor-infiltrating lymphocytes (TILs), programmed cell death protein-1 (PD-1), and programmed death ligand-1 (PD-L1) can identify tumors with aggressive characteristics that can be downgraded regarding the need for RT.

methodsThe SweBCG91RT trial included 1178 patients with stage I-IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT, and followed for a median time of 15.2 years. Immunohistochemical analyses of TILs, PD-1, and PD-L1 were performed. An activated immune response was defined as stromal TILs ≥10% and PD-1 and/or PD-L1 expression in ≥1% of lymphocytes. Tumors were categorized as high-risk or low-risk using assessments of histological grade and proliferation as measured by gene expression. The risk of ipsilateral breast tumor recurrence (IBTR) and benefit of RT were then analyzed with 10 years follow-up based on the integration of immune activation and tumor-intrinsic risk group.

resultsAmong high-risk tumors, an activated immune infiltrate was associated with a reduced risk of IBTR (HR 0.34, 95% CI 0.16 to 0.73, p=0.006). The incidence of IBTR in this group was 12.1% (5.6-25.0) without RT and 4.4% (1.1-16.3) with RT. In contrast, the incidence of IBTR in the high-risk group without an activated immune infiltrate was 29.6% (21.4-40.2) without RT and 12.8% (6.6-23.9) with RT. Among low-risk tumors, no evidence of a favorable prognostic effect of an activated immune infiltrate was seen (HR 2.0, 95% CI 0.87 to 4.6, p=0.100).

conclusionsIntegrating histological grade and immunological biomarkers can identify tumors with aggressive characteristics but a low risk of IBTR despite a lack of RT boost and systemic therapy. Among high-risk tumors, the risk reduction of IBTR conferred by an activated immune infiltrate is comparable to treatment with RT. These findings may apply to cohorts dominated by estrogen receptor-positive tumors.

Indexed as

Breast NeoplasmsB7-H1 AntigenBiomarkersFemaleHumansLigandsLymphocytes, Tumor-InfiltratingNeoplasm Recurrence, LocalProgrammed Cell Death 1 ReceptorB7-H1 AntigenBiomarkersLigandsProgrammed Cell Death 1 ReceptorClinical Trials, Phase III as TopicGenome InstabilityRadiotherapyTumor BiomarkersTumor Microenvironment

Identifiers

PMID37208129
PMCPMC10201214
OpenAlexW4377096022

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LicenceCC BY
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Registered trials

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.