Evidence map›Paper›PMID 27117582›Full record

ArticleBreast cancer research : BCR2016

Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis.

Renata Duchnowska, Rafał Pęksa, Barbara Radecka, Tomasz Mandat, Tomasz Trojanowski, Bożena Jarosz, Bogumiła Czartoryska-Arłukowicz, Wojciech P Olszewski, Waldemar Och, Ewa Kalinka-Warzocha and 6 more

Open access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
10.0field-weighted citation impact, top 1% 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.

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

74 citing papers in PubMed, 128 citations in OpenAlex.

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  6. Chinese Society of Clinical Oncology breast cancer expert consensus on the diagnosis and treatment of breast cancer brain metastasis (2025).Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026
    Review
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  8. Biological profile of breast cancer brain metastasis.Acta neuropathologica communications · 2025
    Review
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  19. The tumor-nerve circuit in breast cancer.Cancer metastasis reviews · 2023
    Review
  20. Review

14 more citing papers are in PubMed but not listed here.

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

16 authors at 5 institutions in 2 countries.

Renata DuchnowskaDepartment of Oncology, Military Institute of Medicine, Szaserów St 128, 04-141, Warsaw, Poland. rdtt@wp.pl.
Rafał PęksaDepartment of Pathology, Medical University of Gdańsk, 7 Dębinki St, 80-211, Gdańsk, Poland.
Barbara RadeckaDepartment of Oncology, Regional Oncology Center, 66a Katowicka St, 45-060, Opole, Poland.
Tomasz MandatDepartment of Neurosurgery, Oncology Center-Institute, 5 Roentgena St, 02-781, Warsaw, Poland.
Tomasz TrojanowskiDepartment of Neurosurgery, Medical University of Lublin, 1 Al. Racławickie, 20-059, Lublin, Poland.
Bożena JaroszDepartment of Neurosurgery, Medical University of Lublin, 1 Al. Racławickie, 20-059, Lublin, Poland.
Bogumiła Czartoryska-ArłukowiczDepartment of Oncology, Regional Oncology Center, 12 Ogrodowa St, 15-027, Białystok, Poland.
Wojciech P OlszewskiDepartment of Pathology, Oncology Center-Institute, 5 Roentgena St, 02-781, Warsaw, Poland.
Waldemar OchDepartment of Neurosurgery, Regional Hospital, 18 Żołnierska St, 10-561, Olsztyn, Poland.
Ewa Kalinka-WarzochaDepartment of Oncology, Regional Oncology Center, 62 Pabianicka St, 93-513, Łódź, Poland.
Wojciech KozłowskiDepartment of Pathology, Military Institute of Medicine, Szaserów St 128, 04-141, Warsaw, Poland.
Anna KowalczykDepartment of Oncology and Radiotherapy, Medical University of Gdańsk, 7 Dębinki St, 80-211, Gdańsk, Poland.
Sherene LoiDivision of Cancer Medicine and Research, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, East Melbourne, VIC, 8006, Australia.
Wojciech BiernatDepartment of Pathology, Medical University of Gdańsk, 7 Dębinki St, 80-211, Gdańsk, Poland.
Jacek JassemDepartment of Oncology and Radiotherapy, Medical University of Gdańsk, 7 Dębinki St, 80-211, Gdańsk, Poland.
Polish Brain Metastasis Consortium
Gdańsk Medical University · PLLublin Oncology Center · PLMedical University of Lublin · PLWojskowy Instytut Medycyny Lotniczej · PLPeter MacCallum Cancer Centre · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA better understanding of immune response in breast cancer brain metastases (BCBM) may prompt new preventive and therapeutic strategies.

methodsImmunohistochemical expression of stromal tumor-infiltrating lymphocytes (TILs: CD4, CD8, CTLA4), macrophage/microglial cells (CD68), programmed cell death protein 1 receptor (PD-1), programmed cell death protein 1 receptor ligand (PD-L)1, PD-L2 and glial fibrillary acid protein was assessed in 84 BCBM and their microenvironment.

resultsMedian survival after BCBM excision was 18.3 months (range 0-99). Median number of CD4+, CD8+ TILs and CD68+ was 49, 69 and 76 per 1 mm(2), respectively. PD-L1 and PD-L2 expression in BCBM was present in 53 % and 36 % of cases, and was not related to BCBM phenotype. PD-1 expression on TILs correlated positively with CD4+ and CD8+ TILs (r = 0.26 and 0.33), and so did CD68+ (r = 0.23 and 0.27, respectively). In the multivariate analysis, survival after BCBM excision positively correlated with PD-1 expression on TILs (hazard ratio (HR) = 0.3, P = 0.003), CD68+ infiltration (HR = 0.2, P < 0.001), brain radiotherapy (HR = 0.1, P < 0.001), endocrine therapy (HR = 0.1, P < 0.001), and negatively with hormone-receptor-negative/human epidermal growth factor receptor 2 (HER2)-positive phenotype of primary tumor (HR = 2.6, P = 0.01), HER2 expression in BCBM (HR = 4.9, P = 0.01).

conclusionsPD-L1 and PD-L2 expression is a common occurrence in BCBM, irrespective of primary tumor and BCBM phenotype. Favorable prognostic impact of PD-1 expression on TILs suggests a beneficial effect of preexisting immunity and implies a potential therapeutic role of immune checkpoint inhibitors in BCBM.

Indexed as

AstrocytesB7-H1 AntigenBiomarkers, TumorBrain NeoplasmsBreast NeoplasmsCombined Modality TherapyFemaleGene ExpressionHumansImmunohistochemistryKaplan-Meier EstimateLymphocytes, Tumor-InfiltratingMicrogliaNeoplasm GradingPhenotypePrognosisB7-H1 AntigenBiomarkers, TumorProgrammed Cell Death 1 ReceptorBrain metastasesBreast cancerLymphocytesPD-1PD-L

Identifiers

PMID27117582
PMCPMC4847231
OpenAlexW2343844322

What OpenQuestion holds

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LicenceCC BY
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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.