Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history
Christoph Engel,
Kerstin Rhiem,
Eric Hahnen,
Sibylle Loibl,
Karsten E. Weber,
Sabine Seiler,
Silke Zachariae,
Jan Hauke,
Barbara Wappenschmidt,
Anke Waha,
Britta Blümcke,
Marion Kiechle,
Alfons Meindl,
Dieter Niederacher,
Claus R. Bartram,
Dorothee Speiser,
Brigitte Schlegelberger,
Norbert Arnold,
Peter Wieacker,
Elena Leinert,
Andrea Gehrig,
Susanne Briest,
Karin Kast,
Olaf Riess,
Günter Emons,
Bernhard H. F. Weber,
Jutta Engel,
Rita K. Schmutzler,
on behalf of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC)
Affiliations
Christoph Engel
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig
Kerstin Rhiem
Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne
Eric Hahnen
Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne
Sibylle Loibl
German Breast Group
Karsten E. Weber
German Breast Group
Sabine Seiler
German Breast Group
Silke Zachariae
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig
Jan Hauke
Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne
Barbara Wappenschmidt
Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne
Anke Waha
Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne
Britta Blümcke
Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne
Marion Kiechle
Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum rechts der Isar, Technical University Munich (TUM)
Alfons Meindl
Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum rechts der Isar, Technical University Munich (TUM)
Dieter Niederacher
Department of Gynecology and Obstetrics, University Hospital of the Heinrich-Heine University
Claus R. Bartram
Institute of Human Genetics, University Hospital, University of Heidelberg
Dorothee Speiser
Zentrum für Familiären Brust- und Eierstockkrebs, Klinik für Gynäkologie mit Brustzentrum, Charité – Universitätsmedizin Berlin
Brigitte Schlegelberger
Department of Human Genetics, Hannover Medical School
Norbert Arnold
Institute of Clinical Molecular Biology/Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel
Peter Wieacker
Institute of Human Genetics, University Hospital Münster
Elena Leinert
Department of Gynecology and Obstetrics, University Hospital Ulm
Andrea Gehrig
Institute of Human Genetics, University Würzburg
Susanne Briest
Center for Hereditary Breast and Ovarian Cancer, University Hospital Leipzig
Karin Kast
Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden
Olaf Riess
Institute of Medical Genetics and Applied Genomics, University of Tübingen
Günter Emons
Klinik für Gynäkologie und Geburtshilfe, Universitätsmedizin
Bernhard H. F. Weber
Institute of Human Genetics, University of Regensburg
Jutta Engel
Munich Cancer Registry (MCR) of the Munich Tumour Centre (TZM), Institute for Medical Information Processing, Biometry and Epidemiology (IBE), University Hospital of Munich, Ludwig-Maximilians-University (LMU)
Rita K. Schmutzler
Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne
on behalf of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC)
Abstract Background There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group. Methods The study comprised 802 women (median age 40 years, range 19–76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation. Results A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20–29 years compared to 6.9% in the age group 60–69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50–2.32, p 10% for women diagnosed below approximately 50 years. Conclusions Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation.
