Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer

Muriel Rolfes; Julika Borde; Kathrin Möllenhoff; Mohamad Kayali; Corinna Ernst; Andrea Gehrig; Christian Sutter; Juliane Ramser; Dieter Niederacher; Judit Horváth; Norbert Arnold; Alfons Meindl; Bernd Auber; Andreas Rump; Shan Wang-Gohrke; Julia Ritter; Julia Hentschel; Holger Thiele; Janine Altmüller; Peter Nürnberg; Kerstin Rhiem; Christoph Engel; Barbara Wappenschmidt; Rita K. Schmutzler; Eric Hahnen; Jan Hauke

doi:10.3390/cancers14133292

Cancers (Jul 2022)

Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer

Muriel Rolfes,
Julika Borde,
Kathrin Möllenhoff,
Mohamad Kayali,
Corinna Ernst,
Andrea Gehrig,
Christian Sutter,
Juliane Ramser,
Dieter Niederacher,
Judit Horváth,
Norbert Arnold,
Alfons Meindl,
Bernd Auber,
Andreas Rump,
Shan Wang-Gohrke,
Julia Ritter,
Julia Hentschel,
Holger Thiele,
Janine Altmüller,
Peter Nürnberg,
Kerstin Rhiem,
Christoph Engel,
Barbara Wappenschmidt,
Rita K. Schmutzler,
Eric Hahnen,
Jan Hauke

Affiliations

Muriel Rolfes: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany
Julika Borde: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany
Kathrin Möllenhoff: Mathematisches Institut, Heinrich-Heine-Universität Duesseldorf, 40225 Duesseldorf, Germany
Mohamad Kayali: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany
Corinna Ernst: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany
Andrea Gehrig: Institute of Human Genetics, University Wuerzburg, 97074 Wuerzburg, Germany
Christian Sutter: Institute of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany
Juliane Ramser: Department of Gynecology and Obstetrics, Technical University Munich, 80333 Munich, Germany
Dieter Niederacher: Department of Gynecology and Obstetrics, University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, Germany
Judit Horváth: Institute for Human Genetics, University Hospital Muenster, 48149 Muenster, Germany
Norbert Arnold: Institute of Clinical Molecular Biology, Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, 24105 Kiel, Germany
Alfons Meindl: Department of Gynecology and Obstetrics, LMU Munich, University Hospital Munich, 80337 Munich, Germany
Bernd Auber: Department of Human Genetics, Hannover Medical School, 30645 Hannover, Germany
Andreas Rump: Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, 01062 Dresden, Germany
Shan Wang-Gohrke: Department of Gynecology and Obstetrics, University of Ulm, 89075 Ulm, Germany
Julia Ritter: Institute of Medical and Human Genetics, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany
Julia Hentschel: Institute of Human Genetics, University of Leipzig Hospitals and Clinics, 04103 Leipzig, Germany
Holger Thiele: Cologne Center for Genomics (CCG) and Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany
Janine Altmüller: Cologne Center for Genomics (CCG) and Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany
Peter Nürnberg: Cologne Center for Genomics (CCG) and Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany
Kerstin Rhiem: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany
Christoph Engel: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107 Leipzig, Germany
Barbara Wappenschmidt: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany
Rita K. Schmutzler: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany
Eric Hahnen: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany
Jan Hauke: Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany

DOI: https://doi.org/10.3390/cancers14133292
Journal volume & issue: Vol. 14, no. 13
p. 3292

Abstract

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Male breast cancer (mBC) is associated with a high prevalence of pathogenic variants (PVs) in the BRCA2 gene; however, data regarding other BC predisposition genes are limited. In this retrospective multicenter study, we investigated the prevalence of PVs in BRCA1/2 and 23 non-BRCA1/2 genes using a sample of 614 patients with mBC, recruited through the centers of the German Consortium for Hereditary Breast and Ovarian Cancer. A high proportion of patients with mBC carried PVs in BRCA2 (23.0%, 142/614) and BRCA1 (4.6%, 28/614). The prevalence of BRCA1/2 PVs was 11.0% in patients with mBC without a family history of breast and/or ovarian cancer. Patients with BRCA1/2 PVs did not show an earlier disease onset than those without. The predominant clinical presentation of tumor phenotypes was estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, and HER2-negative (77.7%); further, 10.2% of the tumors were triple-positive, and 1.2% were triple-negative. No association was found between ER/PR/HER2 status and BRCA1/2 PV occurrence. Comparing the prevalence of protein-truncating variants (PTVs) between patients with mBC and control data (ExAC, n = 27,173) revealed significant associations of PTVs in both BRCA1 and BRCA2 with mBC (BRCA1: OR = 17.04, 95% CI = 10.54–26.82, p −5; BRCA2: OR = 77.71, 95% CI = 58.71–102.33, p −5). A case-control investigation of 23 non-BRCA1/2 genes in 340 BRCA1/2-negative patients and ExAC controls revealed significant associations of PTVs in CHEK2, PALB2, and ATM with mBC (CHEK2: OR = 3.78, 95% CI = 1.59–7.71, p = 0.002; PALB2: OR = 14.77, 95% CI = 5.02–36.02, p −5; ATM: OR = 3.36, 95% CI = 0.89–8.96, p = 0.04). Overall, our findings support the benefit of multi-gene panel testing in patients with mBC irrespective of their family history, age at disease onset, and tumor phenotype.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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