Universität zu Köln

Rolfes, Muriel, Borde, Julika, Moellenhoff, Kathrin, Kayali, Mohamad ORCID: 0000-0003-2092-5695, Ernst, Corinna ORCID: 0000-0001-7756-8815, Gehrig, Andrea, Sutter, Christian ORCID: 0000-0003-4051-5888, Ramser, Juliane, Niederacher, Dieter, Horvath, Judit, Arnold, Norbert, Meindl, Alfons, Auber, Bernd, Rump, Andreas, Wang-Gohrke, Shan, Ritter, Julia, Hentschel, Julia, Thiele, Holger, Altmueller, Janine, Nuernberg, Peter, Rhiem, Kerstin, Engel, Christoph ORCID: 0000-0002-7247-282X, Wappenschmidt, Barbara, Schmutzler, Rita K., Hahnen, Eric and Hauke, Jan ORCID: 0000-0001-8236-4075 (2022). Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer. Cancers, 14 (13). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary Male breast cancer (mBC) is a rare disease associated with a high prevalence of pathogenic germline variants (PVs) in the BRCA2 gene. However, data regarding other breast cancer (BC) predisposition genes are limited or conflicting. We investigated the prevalence of PVs in BRCA1/2 and 23 other cancer predisposition genes using an overall study sample of 614 patients with mBC. A high proportion of patients with mBC carried pathogenic germline variants in BRCA2 (23.0%, 142/614) and BRCA1 (4.6%, 28/614). A BRCA1/2 PV prevalence of 11.0% was identified 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. Case-control analyses revealed significant associations of protein-truncating variants in BRCA1, BRCA2, CHEK2, PALB2, and ATM with mBC. Our findings support the benefit of multi-gene panel testing in patients with mBC. 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 < 10(-5); BRCA2: OR = 77.71, 95% CI = 58.71-102.33, p < 10(-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 < 10(-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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rolfes, Muriel UNSPECIFIED UNSPECIFIED UNSPECIFIED Borde, Julika UNSPECIFIED UNSPECIFIED UNSPECIFIED Moellenhoff, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kayali, Mohamad UNSPECIFIED orcid.org/0000-0003-2092-5695 UNSPECIFIED Ernst, Corinna UNSPECIFIED orcid.org/0000-0001-7756-8815 UNSPECIFIED Gehrig, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Sutter, Christian UNSPECIFIED orcid.org/0000-0003-4051-5888 UNSPECIFIED Ramser, Juliane UNSPECIFIED UNSPECIFIED UNSPECIFIED Niederacher, Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED Horvath, Judit UNSPECIFIED UNSPECIFIED UNSPECIFIED Arnold, Norbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Meindl, Alfons UNSPECIFIED UNSPECIFIED UNSPECIFIED Auber, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Rump, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang-Gohrke, Shan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ritter, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hentschel, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Rhiem, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Engel, Christoph UNSPECIFIED orcid.org/0000-0002-7247-282X UNSPECIFIED Wappenschmidt, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmutzler, Rita K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hahnen, Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Hauke, Jan UNSPECIFIED orcid.org/0000-0001-8236-4075 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-695895
DOI:	10.3390/cancers14133292
Journal or Publication Title:	Cancers
Volume:	14
Number:	13
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SEQUENCE VARIANTS; BRCA2; RISK; CLASSIFICATION; MUTATIONS; INSIGHTS; GENETICS; GENES; PALB2 Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69589