Rolfes Muriel, Borde Julika, Möllenhoff Kathrin, Kayali Mohamad, Ernst Corinna, Gehrig Andrea, Sutter Christian, Ramser Juliane, Niederacher Dieter, Horváth Judit, Arnold Norbert, Meindl Alfons, Auber Bernd, Rump Andreas, Wang-Gohrke Shan, Ritter Julia, Hentschel Julia, Thiele Holger, Altmüller Janine, Nürnberg Peter, Rhiem Kerstin, Engel Christoph, Wappenschmidt Barbara, Schmutzler Rita K, Hahnen Eric, Hauke Jan
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.
Mathematisches Institut, Heinrich-Heine-Universität Duesseldorf, 40225 Duesseldorf, Germany.
Cancers (Basel). 2022 Jul 5;14(13):3292. doi: 10.3390/cancers14133292.
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.
男性乳腺癌（mBC）与BRCA2基因中高致病性变异（PVs）患病率相关；然而，关于其他乳腺癌易感基因的数据有限。在这项回顾性多中心研究中，我们使用通过德国遗传性乳腺癌和卵巢癌联盟中心招募的614例mBC患者样本，调查了BRCA1/2和23个非BRCA1/2基因中PVs的患病率。高比例的mBC患者携带BRCA2（23.0%，142/614）和BRCA1（4.6%，28/614）的PVs。在无乳腺癌和/或卵巢癌家族史的mBC患者中，BRCA1/2 PVs的患病率为11.0%。携带BRCA1/2 PVs的患者与未携带的患者相比，疾病发病时间并无更早。肿瘤表型的主要临床表现为雌激素受体（ER）阳性、孕激素受体（PR）阳性和HER2阴性（77.7%）；此外，10.2%的肿瘤为三阳性，1.2%为三阴性。未发现ER/PR/HER2状态与BRCA1/2 PVs发生之间存在关联。比较mBC患者与对照数据（ExAC，n = 27,173）中蛋白质截短变异（PTVs）的患病率，发现BRCA1和BRCA2中的PTVs与mBC均存在显著关联（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）。对340例BRCA1/2阴性患者和ExAC对照中的23个非BRCA1/2基因进行病例对照研究，发现CHEK2、PALB2和ATM中的PTVs与mBC存在显著关联（CHEK2：OR = 3.78，95% CI = 1.
