Ulrich Bick1, Christoph Engel2, Barbara Krug3, Walter Heindel4, Eva M Fallenberg5, Kerstin Rhiem6, David Maintz3, Michael Golatta7, Dorothee Speiser8, Dorothea Rjosk-Dendorfer5, Irina Lämmer-Skarke9, Frederic Dietzel10, Karl Werner Fritz Schäfer11, Elena Leinert12, Stefanie Weigel4, Stephanie Sauer13, Stefanie Pertschy14, Thomas Hofmockel15, Anne Hagert-Winkler16, Karin Kast17,18,19, Anne Quante20, Alfons Meindl21, Marion Kiechle20, Markus Loeffler2, Rita K Schmutzler6. 1. Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany. ulrich.bick@charite.de. 2. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany. 3. Department of Diagnostic and Interventional Radiology, University Hospital Cologne, Cologne, Germany. 4. Institute of Clinical Radiology and Reference Center for Mammography Münster, University of Münster and University Hospital Münster, Münster, Germany. 5. Department of Radiology, University of Munich, Campus Großhadern, Munich, Germany. 6. Center of Familial Breast and Ovarian Cancer, University Hospital Cologne, Cologne, Germany. 7. Breast Unit, Ruprecht-Karls University Heidelberg, Heidelberg, Germany. 8. Department of Gynecology with Breast Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 9. Department of Radiology, Technical University Munich, University Hospital Rechts der Isar, Munich, Germany. 10. Medical Faculty, Department of Diagnostic and Interventional Radiology, University Düsseldorf, Düsseldorf, Germany. 11. Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. 12. Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany. 13. Department of Diagnostic and Interventional Radiology, University Hospital Würzburg, Würzburg, Germany. 14. Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany. 15. Medical Faculty and University Hospital Carl Gustav Carus, Department of Radiology, Technische Universität Dresden, Dresden, Germany. 16. Department of Diagnostic and Interventional Radiology, Leipzig University Hospital, Leipzig, Germany. 17. Medical Faculty and University Hospital Carl Gustav Carus, Department of Gynecology and Obstetrics, Technische Universität Dresden, Dresden, Germany. 18. National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany. 19. German Cancer Consortium (DKTK), Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany. 20. Department of Gynecology and Obstetrics, Technical University Munich, University Hospital Rechts der Isar, Munich, Germany. 21. Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich, Germany.
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.
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.
Entities:
Keywords:
BRCA1 gene; BRCA2 gene; Breast cancer; Early detection of cancer; Hereditary breast and ovarian cancer syndrome; Magnetic resonance imaging
Authors: Markus Müller-Schimpfle; Werner Bader; Pascal Baltzer; Maria Bernathova; Michael Fuchsjäger; Michael Golatta; Thomas H Helbich; Karin Hellerhoff; Sylvia H Heywang-Köbrunner; Claudia Kurtz; Alexander Mundinger; Katja C Siegmann-Luz; Per Skaane; Chistine Solbach; Stefanie Weigel Journal: Breast Care (Basel) Date: 2019-10-02 Impact factor: 2.860
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