Evidence map›Paper›PMID 29522266›Full record

ArticleCancer medicine2018

Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer.

Jan Hauke, Judit Horvath, Eva Groß, Andrea Gehrig, Ellen Honisch, Karl Hackmann, Gunnar Schmidt, Norbert Arnold, Ulrike Faust, Christian Sutter and 35 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 4 pooled it
15.0field-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

97 citing papers in PubMed, 4 syntheses or guidelines pooled it, 162 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Review
  8. Impact of germlineMolecular therapy. Oncology · 2026
    Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Moderate-Low Risk Breast Cancer Gene Expression in a Romanian Population.International journal of molecular sciences · 2025
    Article
  17. Article
  18. Article
  19. Genetic landscape of Romanian PPGLs.Journal of cellular and molecular medicine · 2024
    Article
  20. Article

37 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

45 authors at 18 institutions in 3 countries.

Jan HaukeCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.ORCID 0000-0001-8236-4075
Judit HorvathInstitute for Human Genetics, University Hospital Muenster, Muenster, Germany.
Eva GroßDepartment of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Andrea GehrigInstitute of Human Genetics, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Ellen HonischDepartment of Gynaecology and Obstetrics, University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany.
Karl HackmannInstitute for Clinical Genetics, Technische Universitaet Dresden, Dresden, Germany.
Gunnar SchmidtDepartment of Human Genetics, Hannover Medical School, Hannover, Germany.
Norbert ArnoldDepartment of Gynaecology and Obstetrics, Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
Ulrike FaustInstitute of Medical Genetics and Applied Genomics, University Hospital Tuebingen, Tuebingen, Germany.
Christian SutterInstitute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
Julia HentschelInstitute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany.
Shan Wang-GohrkeDepartment of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
Mateja SmogavecInstitute of Human Genetics, University Medical Center, Georg August University, Goettingen, Germany.
Bernhard H F WeberInstitute of Human Genetics, University of Regensburg, Regensburg, Germany.
Nana Weber-LassalleCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Konstantin Weber-LassalleCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Julika BordeCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Corinna ErnstCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Janine AltmüllerCologne Center for Genomics, University of Cologne, Cologne, Germany.
Alexander E VolkInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Holger ThieleCologne Center for Genomics, University of Cologne, Cologne, Germany.
Verena HübbelCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Peter NürnbergCologne Center for Genomics, University of Cologne, Cologne, Germany.
Katharina KeuppCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Beatrix VersmoldCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Esther PohlCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Christian KubischInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sabine GrillDepartment of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Victoria PaulInstitute for Human Genetics, University Hospital Muenster, Muenster, Germany.
Natalie HeroldCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Nadine LicheyInstitute for Human Genetics, University Hospital Muenster, Muenster, Germany.
Kerstin RhiemCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Nina DitschDepartment of Obstetrics and Gynaecology, Ludwig-Maximilians-University of Munich, Munich, Germany.
Christian RuckertInstitute for Human Genetics, University Hospital Muenster, Muenster, Germany.
Barbara WappenschmidtCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Bernd AuberDepartment of Human Genetics, Hannover Medical School, Hannover, Germany.
Andreas RumpInstitute for Clinical Genetics, Technische Universitaet Dresden, Dresden, Germany.
Dieter NiederacherDepartment of Gynaecology and Obstetrics, University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany.
Thomas HaafInstitute of Human Genetics, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Juliane RamserDepartment of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Bernd DworniczakInstitute for Human Genetics, University Hospital Muenster, Muenster, Germany.
Christoph EngelInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Alfons MeindlDepartment of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Rita K SchmutzlerCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Eric HahnenCenter for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.ORCID 0000-0002-1152-8367
University Hospital Cologne · DEUniversity Hospital Münster · DETUM Klinikum · DEUniversity of Cologne · DEDüsseldorf University Hospital · DEMedizinische Hochschule Hannover · DETechnische Universität Dresden · DEUniversität Hamburg · DEUniversity of Würzburg · DEChristian-Albrechts-Universität zu Kiel · DEHeidelberg University · DELeipzig University of Applied Sciences · DELudwig-Maximilians-Universität München · DEUniversity Hospital Leipzig · DEUniversity Hospital Ulm · DEUniversity of Göttingen · DEUniversity of Regensburg · DEUniversity of Tübingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The prevalence of germ line mutations in non-BRCA1/2 genes associated with hereditary breast cancer (BC) is low, and the role of some of these genes in BC predisposition and pathogenesis is conflicting. In this study, 5589 consecutive BC index patients negative for pathogenic BRCA1/2 mutations and 2189 female controls were screened for germ line mutations in eight cancer predisposition genes (ATM, CDH1, CHEK2, NBN, PALB2, RAD51C, RAD51D, and TP53). All patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germ line testing. The highest mutation prevalence was observed in the CHEK2 gene (2.5%), followed by ATM (1.5%) and PALB2 (1.2%). The mutation prevalence in each of the remaining genes was 0.3% or lower. Using Exome Aggregation Consortium control data, we confirm significant associations of heterozygous germ line mutations with BC for ATM (OR: 3.63, 95%CI: 2.67-4.94), CDH1 (OR: 17.04, 95%CI: 3.54-82), CHEK2 (OR: 2.93, 95%CI: 2.29-3.75), PALB2 (OR: 9.53, 95%CI: 6.25-14.51), and TP53 (OR: 7.30, 95%CI: 1.22-43.68). NBN germ line mutations were not significantly associated with BC risk (OR:1.39, 95%CI: 0.73-2.64). Due to their low mutation prevalence, the RAD51C and RAD51D genes require further investigation. Compared with control datasets, predicted damaging rare missense variants were significantly more prevalent in CHEK2 and TP53 in BC index patients. Compared with the overall sample, only TP53 mutation carriers show a significantly younger age at first BC diagnosis. We demonstrate a significant association of deleterious variants in the CHEK2, PALB2, and TP53 genes with bilateral BC. Both, ATM and CHEK2, were negatively associated with triple-negative breast cancer (TNBC) and estrogen receptor (ER)-negative tumor phenotypes. A particularly high CHEK2 mutation prevalence (5.2%) was observed in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors.

Indexed as

Biomarkers, TumorGenes, BRCA1Genes, BRCA2AdultAgedAged, 80 and overCase-Control StudiesFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenetic TestingGenetic VariationHereditary Breast and Ovarian Cancer SyndromeHumansMiddle AgedOdds RatioBiomarkers, TumorBreast cancer predispositionhereditary breast cancer

Identifiers

PMID29522266
PMCPMC5911592
OpenAlexW2789404207

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.