Evidence map›Paper›PMID 42104457›Full record

ArticleGenome medicine2026

The contribution of rare germline variants to the immune landscape of breast cancer.

Felipe Rojas-Rodríguez, Sander Canisius, Renske Keeman, Aaron J Bernstein, Amber N Hurson, Thomas U Ahearn, Irene L Andrulis, Antonis C Antoniou, Sabine Behrens, Katarzyna Białkowska and 38 more

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Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

48 authors.

Felipe Rojas-RodríguezDivision of Molecular Pathology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, 1066 CX, the Netherlands.
Sander CanisiusDivision of Molecular Pathology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, 1066 CX, the Netherlands.
Renske KeemanDivision of Molecular Pathology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, 1066 CX, the Netherlands.
Aaron J BernsteinDepartment of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, CB1 8RN, UK.
Amber N HursonDivision of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA.
Thomas U AhearnDivision of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA.
Irene L AndrulisFred A. Litwin Center for Cancer Genetics Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital Toronto, Toronto, ON, M5G 1X5, Canada.
Antonis C AntoniouDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, CB1 8RN, UK.
Sabine BehrensDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.
Katarzyna BiałkowskaDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, 71-252, Poland.
Fiona M BlowsDepartment of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, CB1 8RN, UK.
Manjeet K BollaDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, CB1 8RN, UK.
Nicola J CampDepartment of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Melissa H CessnaDepartment of Pathology and Intermountain Biorepository, Intermountain Health, Murray, UT, 84123, USA.
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA.
Joe DennisDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, CB1 8RN, UK.
Peter DevileeDepartment of Pathology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands.
Alison M DunningDepartment of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, CB1 8RN, UK.
Jacek GronwaldDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, 71-252, Poland.
Ute HamannMolecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.
Antoinette HollestelleDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, 3015 GD, the Netherlands.
Maartje J HooningDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, 3015 GD, the Netherlands.
Hugo M HorlingsDepartment of Pathology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, 1066 CX, the Netherlands.
Agnes JagerDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, 3015 GD, the Netherlands.
Anna JakubowskaDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, 71-252, Poland.
Brandt JonesDepartment of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Rudolf KaaksDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.
Marleen KokDepartment of Medical Oncology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, 1066 CX, the Netherlands.
Jolanta LissowskaDepartment of Cancer Epidemiology and Prevention, M Sklodowska-Curie National Research Oncology Institute, Warsaw, 02-034, Poland.
Jan LubińskiDepartment of Genetics and Pathology, Pomeranian Medical University, Szczecin, 71-252, Poland.
Mehdi ManoochehriMolecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.
Jodi L MillerHistopathology/ISH Core Facility, Cancer Research, UK Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, UK.
Noor MuhammadDepartment of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, 54000, Pakistan.
Anna Marie MulliganDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Nadia ObiInstitute for Occupational and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany.
Muhammad U RashidMolecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.
Hans-Peter SinnInstitute of Pathology, Heidelberg University Hospital, Heidelberg, 69120, Germany.
Carolien H M van DeurzenDepartment of Pathology, Erasmus University Medical Center, Rotterdam, 3015 CN, the Netherlands.
Qin WangDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, CB1 8RN, UK.
Justin A WilliamsDepartment of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Xiaohong R YangDivision of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA.
Douglas F EastonDepartment of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, CB1 8RN, UK.
H Raza AliCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, UK.
Montserrat García-ClosasDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, SM2 5NG, UK.
Paul D P PharoahDepartment of Computational Biomedicine, Cedars-Sinai Health Sciences University, West Hollywood, CA, 90069, USA.
Mustapha Abubakar *Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA.
Marjanka K Schmidt *Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, 1066 CX, the Netherlands. mk.schmidt@nki.nl.

Funding

Core-001U01CA164920 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Irene Andrulis, Sarah Violet Colonna · 2018 to 2026
$17.0M
Shared Genomic Segment Analysis and Tumor Subtyping in High-Risk BrCa PedigreesR01CA163353 · NCI · UNIVERSITY OF UTAH · PI CAMP, NICOLA J. · 2012 to 2016
$2.9M
Cancer Research UK C490/A10124Cancer Research UK C490/A16561Cancer Research UK PPRPGM-NOV20\100002Horizon 2020 Framework Programme 633784NCI NIH HHS R01 CA163353NCI NIH HHS U01 CA164920Wellcome Trust V203477/Z/16/Z
6 · The paper itself

Abstract

backgroundMany breast cancer predisposition genes are involved in DNA damage repair, leading to genome instability that can impact immunosurveillance, neoantigen formation, and the composition of the tumor immune microenvironment.

methodsHere, we explored associations between germline protein truncating variants (PTVs) in 34 (putative) breast cancer predisposition genes, of which 26 involved in DNA damage repair, with the abundance of four immune cell markers, i.e., CD8 + , FOXP3 + , CD20 + and CD163 + , across 7,969 invasive breast tumors of women of European ancestry.

resultsThe most apparent associations were those of CD163, a marker of M2-like tumor-associated macrophages, with genes involved in double- and single-strand break DNA repair, and with the 12 known breast cancer predisposition genes combined. Specifically, DNA damage repair genes, BRCA1, BRCA2, PALB2, RAD51D, and MSH6 were associated with a 1.3 to twofold abundance of CD163-positive cells. Estrogen receptor status was found to mediate associations to a limited extent.

conclusionsOur findings support a role of rare pathogenic germline variants involved in DNA damage repair, and particularly those predisposing to breast cancer, in the immune landscape of breast tumors. These insights may help guide the development of immunomodulatory strategies for breast cancer prevention and treatment.

Indexed as

Breast NeoplasmsGenetic Predisposition to DiseaseGerm-Line MutationAntigens, CDAntigens, Differentiation, MyelomonocyticCD163 AntigenDNA RepairFemaleHumansReceptors, Cell SurfaceTumor MicroenvironmentAntigens, CDAntigens, Differentiation, MyelomonocyticCD163 AntigenReceptors, Cell SurfaceHomologous recombination repair, macrophagesRare germline variantsTumor immune microenvironment

Identifiers

PMID42104457
PMCPMC13330082

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