Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer
Male breast cancer (mBC) is associated with a high prevalence of pathogenic variants (PVs) in the <i>BRCA2</i> gene; however, data regarding other BC predisposition genes are limited. In this retrospective multicenter study, we investigated the prevalence of PVs in <i>BRCA1/2</i...
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MDPI AG
2022-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/13/3292 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Muriel Rolfes |
| collection | DOAJ |
| description | Male breast cancer (mBC) is associated with a high prevalence of pathogenic variants (PVs) in the <i>BRCA2</i> gene; however, data regarding other BC predisposition genes are limited. In this retrospective multicenter study, we investigated the prevalence of PVs in <i>BRCA1/2</i> and 23 non-<i>BRCA1/2</i> 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 <i>BRCA2</i> (23.0%, 142/614) and <i>BRCA1</i> (4.6%, 28/614). The prevalence of <i>BRCA1/2</i> PVs was 11.0% in patients with mBC without a family history of breast and/or ovarian cancer. Patients with <i>BRCA1/2</i> 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 <i>BRCA1/2</i> 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 <i>BRCA1</i> and <i>BRCA2</i> with mBC (<i>BRCA1</i>: OR = 17.04, 95% CI = 10.54–26.82, <i>p</i> < 10<sup>−5</sup>; <i>BRCA2</i>: OR = 77.71, 95% CI = 58.71–102.33, <i>p</i> < 10<sup>−5</sup>). A case-control investigation of 23 non-<i>BRCA1/2</i> genes in 340 <i>BRCA1/2</i>-negative patients and ExAC controls revealed significant associations of PTVs in <i>CHEK2</i>, <i>PALB2</i>, and <i>ATM</i> with mBC (<i>CHEK2:</i> OR = 3.78, 95% CI = 1.59–7.71, <i>p</i> = 0.002; <i>PALB2</i>: OR = 14.77, 95% CI = 5.02–36.02, <i>p</i> < 10<sup>−5</sup>; <i>ATM</i>: OR = 3.36, 95% CI = 0.89–8.96, <i>p</i> = 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. |
| first_indexed | 2024-03-09T22:02:13Z |
| format | Article |
| id | doaj.art-0ceb35ffabcf458e8aa13b45efcc0b3f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:02:13Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0ceb35ffabcf458e8aa13b45efcc0b3f2023-11-23T19:47:31ZengMDPI AGCancers2072-66942022-07-011413329210.3390/cancers14133292Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian CancerMuriel Rolfes0Julika Borde1Kathrin Möllenhoff2Mohamad Kayali3Corinna Ernst4Andrea Gehrig5Christian Sutter6Juliane Ramser7Dieter Niederacher8Judit Horváth9Norbert Arnold10Alfons Meindl11Bernd Auber12Andreas Rump13Shan Wang-Gohrke14Julia Ritter15Julia Hentschel16Holger Thiele17Janine Altmüller18Peter Nürnberg19Kerstin Rhiem20Christoph Engel21Barbara Wappenschmidt22Rita K. Schmutzler23Eric Hahnen24Jan Hauke25Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, GermanyCenter for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, GermanyMathematisches Institut, Heinrich-Heine-Universität Duesseldorf, 40225 Duesseldorf, GermanyCenter for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, GermanyCenter for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, GermanyInstitute of Human Genetics, University Wuerzburg, 97074 Wuerzburg, GermanyInstitute of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, GermanyDepartment of Gynecology and Obstetrics, Technical University Munich, 80333 Munich, GermanyDepartment of Gynecology and Obstetrics, University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyInstitute for Human Genetics, University Hospital Muenster, 48149 Muenster, GermanyInstitute of Clinical Molecular Biology, Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, 24105 Kiel, GermanyDepartment of Gynecology and Obstetrics, LMU Munich, University Hospital Munich, 80337 Munich, GermanyDepartment of Human Genetics, Hannover Medical School, 30645 Hannover, GermanyInstitute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, 01062 Dresden, GermanyDepartment of Gynecology and Obstetrics, University of Ulm, 89075 Ulm, GermanyInstitute of Medical and Human Genetics, Charité-Universitätsmedizin Berlin, 13353 Berlin, GermanyInstitute of Human Genetics, University of Leipzig Hospitals and Clinics, 04103 Leipzig, GermanyCologne Center for Genomics (CCG) and Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, GermanyCologne Center for Genomics (CCG) and Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, GermanyCologne Center for Genomics (CCG) and Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, GermanyCenter for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, GermanyInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107 Leipzig, GermanyCenter for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, GermanyCenter for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, GermanyCenter for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, GermanyCenter for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, GermanyMale breast cancer (mBC) is associated with a high prevalence of pathogenic variants (PVs) in the <i>BRCA2</i> gene; however, data regarding other BC predisposition genes are limited. In this retrospective multicenter study, we investigated the prevalence of PVs in <i>BRCA1/2</i> and 23 non-<i>BRCA1/2</i> 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 <i>BRCA2</i> (23.0%, 142/614) and <i>BRCA1</i> (4.6%, 28/614). The prevalence of <i>BRCA1/2</i> PVs was 11.0% in patients with mBC without a family history of breast and/or ovarian cancer. Patients with <i>BRCA1/2</i> 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 <i>BRCA1/2</i> 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 <i>BRCA1</i> and <i>BRCA2</i> with mBC (<i>BRCA1</i>: OR = 17.04, 95% CI = 10.54–26.82, <i>p</i> < 10<sup>−5</sup>; <i>BRCA2</i>: OR = 77.71, 95% CI = 58.71–102.33, <i>p</i> < 10<sup>−5</sup>). A case-control investigation of 23 non-<i>BRCA1/2</i> genes in 340 <i>BRCA1/2</i>-negative patients and ExAC controls revealed significant associations of PTVs in <i>CHEK2</i>, <i>PALB2</i>, and <i>ATM</i> with mBC (<i>CHEK2:</i> OR = 3.78, 95% CI = 1.59–7.71, <i>p</i> = 0.002; <i>PALB2</i>: OR = 14.77, 95% CI = 5.02–36.02, <i>p</i> < 10<sup>−5</sup>; <i>ATM</i>: OR = 3.36, 95% CI = 0.89–8.96, <i>p</i> = 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.https://www.mdpi.com/2072-6694/14/13/3292breast neoplasmsmale breast cancerbreast cancer predisposition genesgenetic testingfamilial breast cancer |
| spellingShingle | 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 Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer Cancers breast neoplasms male breast cancer breast cancer predisposition genes genetic testing familial breast cancer |
| title | Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer |
| title_full | Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer |
| title_fullStr | Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer |
| title_full_unstemmed | Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer |
| title_short | Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer |
| title_sort | prevalence of cancer predisposition germline variants in male breast cancer patients results of the german consortium for hereditary breast and ovarian cancer |
| topic | breast neoplasms male breast cancer breast cancer predisposition genes genetic testing familial breast cancer |
| url | https://www.mdpi.com/2072-6694/14/13/3292 |
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