TY  - JOUR
A1  - Rolfes, Muriel
A1  - Borde, Julika
A1  - Möllenhoff, Kathrin
A1  - Kayali, Mohamad
A1  - Ernst, Corinna
A1  - Gehrig, Andrea
A1  - Sutter, Christian
A1  - Ramser, Juliane
A1  - Niederacher, Dieter
A1  - Horváth, Judit
A1  - Arnold, Norbert
A1  - Meindl, Alfons
A1  - Auber, Bernd
A1  - Rump, Andreas
A1  - Wang-Gohrke, Shan
A1  - Ritter, Julia
A1  - Hentschel, Julia
A1  - Thiele, Holger
A1  - Altmüller, Janine
A1  - Nürnberg, Peter
A1  - Rhiem, Kerstin
A1  - Engel, Christoph
A1  - Wappenschmidt, Barbara
A1  - Schmutzler, Rita K.
A1  - Hahnen, Eric
A1  - Hauke, Jan
T1  - Prevalence of cancer predisposition germline variants in male breast cancer patients: results of the German Consortium for Hereditary Breast and Ovarian Cancer
JF  - Cancers
N2  - 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.
KW  - breast neoplasms
KW  - male breast cancer
KW  - breast cancer predisposition genes
KW  - genetic testing
KW  - familial breast cancer
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281758
SN  - 2072-6694
VL  - 14
IS  - 13
ER  - 
TY  - JOUR
A1  - Hauke, Jan
A1  - Horvath, Judit
A1  - Groß, Eva
A1  - Gehrig, Andrea
A1  - Honisch, Ellen
A1  - Hackmann, Karl
A1  - Schmidt, Gunnar
A1  - Arnold, Norbert
A1  - Faust, Ulrike
A1  - Sutter, Christian
A1  - Hentschel, Julia
A1  - Wang-Gohrke, Shan
A1  - Smogavec, Mateja
A1  - Weber, Bernhard H. F.
A1  - Weber-Lassalle, Nana
A1  - Weber-Lassalle, Konstantin
A1  - Borde, Julika
A1  - Ernst, Corinna
A1  - Altmüller, Janine
A1  - Volk, Alexander E.
A1  - Thiele, Holger
A1  - Hübbel, Verena
A1  - Nürnberg, Peter
A1  - Keupp, Katharina
A1  - Versmold, Beatrix
A1  - Pohl, Esther
A1  - Kubisch, Christian
A1  - Grill, Sabine
A1  - Paul, Victoria
A1  - Herold, Natalie
A1  - Lichey, Nadine
A1  - Rhiem, Kerstin
A1  - Ditsch, Nina
A1  - Ruckert, Christian
A1  - Wappenschmidt, Barbara
A1  - Auber, Bernd
A1  - Rump, Andreas
A1  - Niederacher, Dieter
A1  - Haaf, Thomas
A1  - Ramser, Juliane
A1  - Dworniczak, Bernd
A1  - Engel, Christoph
A1  - Meindl, Alfons
A1  - Schmutzler, Rita K.
A1  - Hahnen, Eric
T1  - Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer
JF  - Cancer Medicine
N2  - The prevalence of germ line mutations in non-BRCA1/2 genes associated with hereditary breast cancer (BC) is low, and the role of some of these genes in BC predisposition and pathogenesis is conflicting. In this study, 5589 consecutive BC index patients negative for pathogenic BRCA1/2 mutations and 2189 female controls were screened for germ line mutations in eight cancer predisposition genes (ATM, CDH1, CHEK2, NBN, PALB2, RAD51C, RAD51D, and TP53). All patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germ line testing. The highest mutation prevalence was observed in the CHEK2 gene (2.5%), followed by ATM (1.5%) and PALB2 (1.2%). The mutation prevalence in each of the remaining genes was 0.3% or lower. Using Exome Aggregation Consortium control data, we confirm significant associations of heterozygous germ line mutations with BC for ATM (OR: 3.63, 95%CI: 2.67–4.94), CDH1 (OR: 17.04, 95%CI: 3.54–82), CHEK2 (OR: 2.93, 95%CI: 2.29–3.75), PALB2 (OR: 9.53, 95%CI: 6.25–14.51), and TP53 (OR: 7.30, 95%CI: 1.22–43.68). NBN germ line mutations were not significantly associated with BC risk (OR:1.39, 95%CI: 0.73–2.64). Due to their low mutation prevalence, the RAD51C and RAD51D genes require further investigation. Compared with control datasets, predicted damaging rare missense variants were significantly more prevalent in CHEK2 and TP53 in BC index patients. Compared with the overall sample, only TP53 mutation carriers show a significantly younger age at first BC diagnosis. We demonstrate a significant association of deleterious variants in the CHEK2, PALB2, and TP53 genes with bilateral BC. Both, ATM and CHEK2, were negatively associated with triple-negative breast cancer (TNBC) and estrogen receptor (ER)-negative tumor phenotypes. A particularly high CHEK2 mutation prevalence (5.2%) was observed in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors.
KW  - breast cancer predisposition
KW  - hereditary breast cancer
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227902
ER  -