|
|||||
|
|
Breast cancer risk in BRCA1/2 mutation carriers and noncarriers under prospective intensified surveillance |
|
| Authors: | Christoph Engel Christine Fischer Silke Zachariae Karolin Bucksch Kerstin Rhiem Jutta Giesecke Natalie Herold Barbara Wappenschmidt Verena Hübbel Monika Maringa Simone Reichstein-Gnielinski Eric Hahnen Claus R. Bartram Nicola Dikow Sarah Schott Dorothee Speiser Denise Horn Eva M. Fallenberg Marion Kiechle Anne S. Quante Anne-Sophie Vesper Tanja Fehm Christoph Mundhenke Norbert Arnold Elena Leinert Walter Just Ulrike Siebers-Renelt Stefanie Weigel Andrea Gehrig Achim Wöckel Brigitte Schlegelberger Stefanie Pertschy Karin Kast Pauline Wimberger Susanne Briest Markus Loeffler Ulrich Bick Rita K. Schmutzler on behalf of the German Consortium for Hereditary Breast Ovarian Cancer (GC-HBOC) |
| Affiliation: | 1. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany;2. Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany;3. Institute of Human Genetics, Ruprecht-Karls University, Heidelberg, Germany;4. Department of Gynaecology, Ruprecht-Karls University, Heidelberg, Germany;5. Department of Gynecology with Breast Center, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany;6. Institute of Medical Genetics and Human Genetics, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany;7. Department of Radiology, University Hospital, LMU Munich, Munich, Germany;8. Department of Gynecology and Obstetrics, University Hospital Rechts der Isar, Technical University Munich, Munich, Germany;9. Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany;10. Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Christian-Albrechts-University Kiel, Kiel, Germany;11. Department of Gynecology and Obstetrics, Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Christian-Albrechts-University Kiel, Kiel, Germany;12. Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany;13. Institute of Human Genetics, University of Ulm, Ulm, Germany;14. Institut für Humangenetik, Universitätsklinikum Münster, Münster, Germany;15. Institute of Clinical Radiology, Medical Faculty, University of Muenster, University Hospital Muenster, Muenster, Germany;16. Institute of Human Genetics, Würzburg University, Würzburg, Germany;17. Department of Obstetrics and Gynecology, Würzburg University Hospital, Würzburg, Germany;18. Department of Human Genetics, Hannover Medical School, Hannover, Germany;19. Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany;20. Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany;21. Department of Obstetrics and Gynecology, University Hospital Leipzig, Leipzig, Germany |
| Abstract: | Comparably little is known about breast cancer (BC) risks in women from families tested negative for BRCA1/2 mutations despite an indicative family history, as opposed to BRCA1/2 mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers of BRCA1/2 mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n = 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n = 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8–70.9%) for BRCA1 mutation carriers, 43.2% (95% CI 32.1–56.3%) for BRCA2 mutation carriers and 15.7% (95% CI 11.9–20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9–29.8) for BRCA1 mutation carriers, 13.5 (95% CI 9.2–19.1) for BRCA2 mutation carriers and 4.9 (95% CI 3.8–6.3) for BRCA1/2 noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6–31.9%) for BRCA1 mutation carriers, 6.6% (95% CI 3.4–12.5%) for BRCA2 mutation carriers and 3.6% (95% CI 2.2–5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women from BRCA1/2 negative families with elevated risk. |
| Keywords: | hereditary breast and ovarian cancer breast cancer risk prospective cohort study surveillance breast imaging |