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High-risk breast cancer surveillance with MRI: 10-year experience from the German consortium for hereditary breast and ovarian cancer

  • Ulrich BickEmail author
  • Christoph Engel
  • Barbara Krug
  • Walter Heindel
  • Eva M. Fallenberg
  • Kerstin Rhiem
  • David Maintz
  • Michael Golatta
  • Dorothee Speiser
  • Dorothea Rjosk-Dendorfer
  • Irina Lämmer-Skarke
  • Frederic Dietzel
  • Karl Werner Fritz Schäfer
  • Elena Leinert
  • Stefanie Weigel
  • Stephanie Sauer
  • Stefanie Pertschy
  • Thomas Hofmockel
  • Anne Hagert-Winkler
  • Karin Kast
  • Anne Quante
  • Alfons Meindl
  • Marion Kiechle
  • Markus Loeffler
  • Rita K. Schmutzler
  • the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC)
Clinical trial

Abstract

Purpose

To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC).

Methods

A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age.

Results

A total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9–93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6–85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6–91.7), p < 0.001. Cancer detection rates (CDRs) and as a result positive predictive values were strongly dependent on type of screening round, risk group and patient age. CDRs ranged from 43.5‰ (95% CI 29.8–62.9) for the first screening round in BRCA2 carriers to 2.9‰ (95% CI 1.3–6.3) for subsequent screening rounds in high-risk non-carriers in the age group 30 to 39 years.

Conclusions

High-risk screening with MRI was successfully implemented in the GC-HBOC with high sensitivity and specificity. Risk prediction and inclusion criteria in high-risk non-carriers need to be adjusted to improve CDRs and thus screening efficacy in these patients.

Keywords

Hereditary breast and ovarian cancer syndrome BRCA1 gene BRCA2 gene Breast cancer Early detection of cancer Magnetic resonance imaging 

Notes

Acknowledgements

The following investigators of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) provided and cared for study patients and/or were involved in the data gathering and analysis: Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Gynecology with Breast Center: Jens-Uwe Blohmer; Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Medical Genetics and Human Genetics: Denise Horn; Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Medical Genetics and Human Genetics: Raymonda Varon-Mateeva; University Hospital Cologne, Center of Familial Breast and Ovarian Cancer: Verena Hübbel, Natalie Herold; University Hospital Cologne, Department of Diagnostic and Interventional Radiology: Michael Püsken; Technische Universität Dresden, Medical Faculty and University Hospital Carl Gustav Carus, Department of Gynecology and Obstetrics: Pauline Wimberger, Cornelia Meisel, Katja Keller; University Düsseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology: Gerald Antoch; University Hospital Düsseldorf, Department of Gynecology and Obstetrics: Anne-Sophie Vesper, Tanja N. Fehm; Hannover Medical School, Department of Human Genetics: Brigitte Schlegelberger, Bernd Auber, Hannah Wallaschek; Ruprecht-Karls University Heidelberg, Breast Unit: Jörg Heil, Sarah Schott; Ruprecht-Karls University Heidelberg, Institute of Human Genetics: Nicola Dikow; UNIVERSITY HOSPITAL SCHLESWIG–HOLSTEIN, Campus Kiel, Department of Gynaecology and Obstetrics: Christoph Mundhenke, Norbert Arnold; University Hospital Schleswig–Holstein, Campus Kiel, Institute of Human Genetics: Almuth Caliebe; University Medical Center Leipzig, Department of Obstetrics and Gynecology: Susanne Briest; University Medical Center Leipzig, Institute of Human Genetics: Johannes Lemke; Technical University Munich, University Hospital rechts der Isar, Department of Gynecology and Obstetrics: Sabine Gril, Katharina Pfeifer, Juliane Ramser; University of Munich, Campus Großhadern, Department of Gynecology and Obstetrics: Sven Mahner, Nina Ditsch, Christine Zeder-Göß; University of Münster and University Hospital Münster, Department of Gynecology and Obstetrics: Joke Tio; University of Münster and University Hospital Münster, Institute of Clinical Radiology and Reference Center for Mammography Münster: Matthias Burg; University of Münster and University Hospital Münster, Institute of Human Genetics: Judith Horvath; Ulm University, Institute of Human Genetics: Reiner Siebert; University Hospital Ulm, Department of Diagnostic and Interventional Radiology: Jasmin Bartholomä; University Hospital Ulm, Department of Gynecology and Obstetrics: Wolfgang Janni; University Hospital Würzburg, Department of Diagnostic and Interventional Radiology: Thorsten Bley; University Hospital Würzburg, Department of Gynecology and Obstetrics: Achim Wöckel; University of Würzburg, Institute of Human Genetics: Thomas Haaf; University of Leipzig, Institute for Medical Informatics, Statistics and Epidemiology: Silke Zachariae, Karolin Bucksch, Ute Enders.

Funding

The study was supported by a grant (110837) from the German Cancer Aid (Deutsche Krebshilfe).

Compliance with ethical standards

Conflict of interest

UB has received patent royalties from Hologic. EMF has received institutional research funding from GE Healthcare and Guerbet and has received speaker honoraria and travel expenses from GE Healthcare, Bayer Healthcare, and Guerbet. KR has received honoraria from AstraZeneca. DM has received speaker honoraria and institutional research funding from Philips. KWFS has received travel expenses from SuperSonic Imagine. KK has received honoraria from Roche, Pfizer, and AstraZeneca and has given expert testimony to and received travel expenses from Roche. MK holds stock or other ownership in Therawis Diagnostics and Meine Busenfreundin GmbH, has received honoraria from AstraZeneca, Celgene, Myriad Genetics, HRA, Stiftung Warentest, has held a consulting or advisory role with AstraZeneca and Celgene, has given expert testimony to Therawis Diagnostics, and has received travel expenses from Myriad Genetics and Celgene. All other authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ulrich Bick
    • 1
    Email author
  • Christoph Engel
    • 2
  • Barbara Krug
    • 3
  • Walter Heindel
    • 4
  • Eva M. Fallenberg
    • 5
  • Kerstin Rhiem
    • 6
  • David Maintz
    • 3
  • Michael Golatta
    • 7
  • Dorothee Speiser
    • 8
  • Dorothea Rjosk-Dendorfer
    • 5
  • Irina Lämmer-Skarke
    • 9
  • Frederic Dietzel
    • 10
  • Karl Werner Fritz Schäfer
    • 11
  • Elena Leinert
    • 12
  • Stefanie Weigel
    • 4
  • Stephanie Sauer
    • 13
  • Stefanie Pertschy
    • 14
  • Thomas Hofmockel
    • 15
  • Anne Hagert-Winkler
    • 16
  • Karin Kast
    • 17
    • 18
    • 19
  • Anne Quante
    • 20
  • Alfons Meindl
    • 21
  • Marion Kiechle
    • 20
  • Markus Loeffler
    • 2
  • Rita K. Schmutzler
    • 6
  • the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC)
  1. 1.Department of RadiologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlinGermany
  2. 2.Institute for Medical Informatics, Statistics and EpidemiologyUniversity of LeipzigLeipzigGermany
  3. 3.Department of Diagnostic and Interventional RadiologyUniversity Hospital CologneCologneGermany
  4. 4.Institute of Clinical Radiology and Reference Center for Mammography MünsterUniversity of Münster and University Hospital MünsterMünsterGermany
  5. 5.Department of RadiologyUniversity of MunichMunichGermany
  6. 6.Center of Familial Breast and Ovarian CancerUniversity Hospital CologneCologneGermany
  7. 7.Breast UnitRuprecht-Karls University HeidelbergHeidelbergGermany
  8. 8.Department of Gynecology with Breast CenterCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlinGermany
  9. 9.Department of RadiologyTechnical University Munich, University Hospital Rechts der IsarMunichGermany
  10. 10.Medical Faculty, Department of Diagnostic and Interventional RadiologyUniversity DüsseldorfDüsseldorfGermany
  11. 11.Department of Radiology and NeuroradiologyUniversity Hospital Schleswig-HolsteinKielGermany
  12. 12.Department of Gynecology and ObstetricsUniversity Hospital UlmUlmGermany
  13. 13.Department of Diagnostic and Interventional RadiologyUniversity Hospital WürzburgWürzburgGermany
  14. 14.Department of Diagnostic and Interventional RadiologyHannover Medical SchoolHannoverGermany
  15. 15.Medical Faculty and University Hospital Carl Gustav Carus, Department of RadiologyTechnische Universität DresdenDresdenGermany
  16. 16.Department of Diagnostic and Interventional RadiologyLeipzig University HospitalLeipzigGermany
  17. 17.Medical Faculty and University Hospital Carl Gustav Carus, Department of Gynecology and ObstetricsTechnische Universität DresdenDresdenGermany
  18. 18.National Center for Tumor Diseases (NCT), Partner Site DresdenDresdenGermany
  19. 19.German Cancer Consortium (DKTK), Dresden, and German Cancer Research Center (DKFZ)HeidelbergGermany
  20. 20.Department of Gynecology and ObstetricsTechnical University Munich, University Hospital Rechts der IsarMunichGermany
  21. 21.Department of Gynecology and ObstetricsUniversity of MunichMunichGermany

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