. 2018 Mar 7;18(1):265.

doi: 10.1186/s12885-018-4029-y.

Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history

Christoph Engel¹, Kerstin Rhiem², Eric Hahnen², Sibylle Loibl^{3

4}, Karsten E Weber³, Sabine Seiler³, Silke Zachariae¹, Jan Hauke², Barbara Wappenschmidt², Anke Waha², Britta Blümcke², Marion Kiechle⁵, Alfons Meindl⁵, Dieter Niederacher⁶, Claus R Bartram⁷, Dorothee Speiser⁸, Brigitte Schlegelberger⁹, Norbert Arnold¹⁰, Peter Wieacker¹¹, Elena Leinert¹², Andrea Gehrig¹³, Susanne Briest¹⁴, Karin Kast^{15

16

17}, Olaf Riess¹⁸, Günter Emons¹⁹, Bernhard H F Weber²⁰, Jutta Engel²¹, Rita K Schmutzler²²; German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC)

Affiliations

¹ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
² Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Kerpener Strasse 34, 50931, Cologne, Germany.
³ German Breast Group, Neu-Isenburg, Germany.
⁴ Centre for Haematology and Oncology Bethanien, Frankfurt, Germany.
⁵ Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum rechts der Isar, Technical University Munich (TUM), Munich, Germany.
⁶ Department of Gynecology and Obstetrics, University Hospital of the Heinrich-Heine University, Düsseldorf, Germany.
⁷ Institute of Human Genetics, University Hospital, University of Heidelberg, Heidelberg, Germany.
⁸ Zentrum für Familiären Brust- und Eierstockkrebs, Klinik für Gynäkologie mit Brustzentrum, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁹ Department of Human Genetics, Hannover Medical School, Hannover, Germany.
¹⁰ Institute of Clinical Molecular Biology/Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
¹¹ Institute of Human Genetics, University Hospital Münster, Münster, Germany.
¹² Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
¹³ Institute of Human Genetics, University Würzburg, Würzburg, Germany.
¹⁴ Center for Hereditary Breast and Ovarian Cancer, University Hospital Leipzig, Leipzig, Germany.
¹⁵ Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
¹⁶ National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.
¹⁷ German Cancer Consortium (DKTK), Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁸ Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
¹⁹ Klinik für Gynäkologie und Geburtshilfe, Universitätsmedizin, Göttingen, Germany.
²⁰ Institute of Human Genetics, University of Regensburg, Regensburg, Germany.
²¹ 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), Munich, Germany.
²² Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Kerpener Strasse 34, 50931, Cologne, Germany. rita.schmutzler@uk-koeln.de.

PMID: 29514593
PMCID: PMC5842578
DOI: 10.1186/s12885-018-4029-y

Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history

Christoph Engel et al. BMC Cancer. 2018.

. 2018 Mar 7;18(1):265.

doi: 10.1186/s12885-018-4029-y.

Authors

Affiliations

¹ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
² Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Kerpener Strasse 34, 50931, Cologne, Germany.
³ German Breast Group, Neu-Isenburg, Germany.
⁴ Centre for Haematology and Oncology Bethanien, Frankfurt, Germany.
⁵ Department of Gynecology and Center for Hereditary Breast and Ovarian Cancer, Klinikum rechts der Isar, Technical University Munich (TUM), Munich, Germany.
⁶ Department of Gynecology and Obstetrics, University Hospital of the Heinrich-Heine University, Düsseldorf, Germany.
⁷ Institute of Human Genetics, University Hospital, University of Heidelberg, Heidelberg, Germany.
⁸ Zentrum für Familiären Brust- und Eierstockkrebs, Klinik für Gynäkologie mit Brustzentrum, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁹ Department of Human Genetics, Hannover Medical School, Hannover, Germany.
¹⁰ Institute of Clinical Molecular Biology/Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany.
¹¹ Institute of Human Genetics, University Hospital Münster, Münster, Germany.
¹² Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
¹³ Institute of Human Genetics, University Würzburg, Würzburg, Germany.
¹⁴ Center for Hereditary Breast and Ovarian Cancer, University Hospital Leipzig, Leipzig, Germany.
¹⁵ Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
¹⁶ National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.
¹⁷ German Cancer Consortium (DKTK), Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁸ Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
¹⁹ Klinik für Gynäkologie und Geburtshilfe, Universitätsmedizin, Göttingen, Germany.
²⁰ Institute of Human Genetics, University of Regensburg, Regensburg, Germany.
²¹ 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), Munich, Germany.
²² Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Kerpener Strasse 34, 50931, Cologne, Germany. rita.schmutzler@uk-koeln.de.

PMID: 29514593
PMCID: PMC5842578
DOI: 10.1186/s12885-018-4029-y

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 < 0.001). gBRCA mutation risk was predicted to be > 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.

Keywords: BRCA1; BRCA2; Hereditary breast and ovarian cancer; Triple-negative breast cancer.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The multicentre GC-HBOC registry and the multicentre GBG GeparSixto trial have been approved by the responsible ethics committees. Written informed consent to be enrolled in the GC-HBOC registry or the GBG GeparSixto trial, respectively, was obtained from all individuals whose data was used for the present analysis.

Consent for publication

Not applicable.

Competing interests

Eric Hahnen, Kerstin Rhiem, Brigitte Schlegelberger, Rita Schmutzler: Advisory Board Astra Zeneca. Sibylle Loibl is member of the editorial board (Associate Editor) of BMC Cancer. All other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Association between age of TNBC diagnosis and gBRCA mutation prevalence. Grey shaded bars indicate the mutation prevalence in the according age group (error bars indicate 95% confidence intervals). The bold curve represents the mutation probability predicted by the logistic regression model (with 95% confidence band, thin curves). The dashed horizontal line depicts the 10% mutation probability, above which gBRCA mutation analysis is recommended

See this image and copyright information in PMC

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Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history

Affiliations

Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history

Authors

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous