Department of Internal Medicine, Acibadem Altunizade Hospital, Altunizade District, Yurtcan St. No: 1, Uskudar, Istanbul, Turkey.
Department of Medical Genetics, Acibadem Mehmet Ali Aydinlar University, School of Medicine, Halkali Merkez, Turgut Ozal Bulvari No: 16, 34303, Kucukcekmece, Istanbul, Turkey.
Breast Cancer Res Treat. 2023 Nov;202(2):297-304. doi: 10.1007/s10549-023-07074-z. Epub 2023 Aug 24.
One of the most important risk factors for hereditary breast and ovarian cancer is young age. We aim to report the frequency of pathogenic/likely pathogenic variants in breast cancer predisposing genes in young (≤ 40 years old) breast cancer patients who undergone 26-gene inherited cancer panel at our Breast Health Center.
Medical records of breast cancer patients who were referred to genetic counseling based on NCCN criteria and were ≤ 40 years of age are reviewed. The frequency of germline pathogenic/likely pathogenic variants who undergone 26-gene inherited cancer panel was analyzed.
Among 414 breast cancer patients who were ≤ 40 years of age, 308 undergone 26-gene inherited cancer panel and 108 had next generation sequencing (NGS)-based BRCA 1 and 2 genetic testing. Median age was 35 (22-40), Family history in first degree relatives was present in 14% of patients. Forty-five percent of patients met one of the NCCN criteria for genetic testing, 41% of them met two criteria, and 14% of patients fulfilled ≥ 3 criteria. Seventy pathogenic/likely pathogenic variants (PV/LPV) were found in 65 (21%) patients. PV/LPs in BRCA genes and non-BRCA genes represented 53% and 44% of all PV/LPVs, accounting for 12% and 10% of patients in the study cohort respectively. Two PVs were present in 5 patients and eleven PVs were novel. The most common PVs were in BRCA 1 (n:18), BRCA 2 (n:19), ATM (n:7), CHEK2 (n:7) and TP53 (n:5) genes. Thirty-one percent of the patients with triple-negative tumors and 25% of the patients with hormone receptor-positive tumors had PV/LPVs with panel testing. Family history in first degree relatives (p = 0.029), the number of met NCCN criteria (p = 0.036) and axillary nodal involvement (p = 0.000) were more common in patients with PVs. When combined with patient group (n:106) who had only BRCA1 and 2 gene testing, 16% of Turkish breast cancer patients ≤ 40 years of age had PVs in BRCA genes.
One fifth of Turkish breast cancer patients ≤ 40 years of age had at least one PV/LPV in breast cancer predisposing genes with 26-gene inherited cancer panel. The frequency of PV/LPVs was higher in triple-negative young-onset patients compared to hormone receptor and Her-2 positive subtypes. Our findings regarding to frequency PV/LPVs in BRCA 1/2 and non-BRCA genes in young-onset breast cancer patients are in line with the literature.
遗传性乳腺癌和卵巢癌最重要的风险因素之一是年龄较轻。我们旨在报告在我们的乳腺健康中心进行 26 基因遗传性癌症panel 的≤40 岁年轻（≤40 岁）乳腺癌患者中乳腺癌易感基因的致病性/可能致病性变异的频率。
回顾了根据 NCCN 标准转介至遗传咨询并≤40 岁的乳腺癌患者的病历。分析了接受 26 基因遗传性癌症 panel 的具有种系致病性/可能致病性变异的患者的频率。
在 414 名≤40 岁的乳腺癌患者中，308 名患者接受了 26 基因遗传性癌症 panel 检测，108 名患者接受了基于下一代测序（NGS）的 BRCA1 和 2 基因检测。中位年龄为 35（22-40）岁，14%的患者有一级亲属的家族史。45%的患者符合 NCCN 基因检测标准之一，41%的患者符合两项标准，14%的患者符合≥3 项标准。在 65 名（21%）患者中发现了 70 个致病性/可能致病性变异（PV/LPV）。BRCA 基因和非 BRCA 基因中的 PV/LPs 分别占所有 PV/LPV 的 53%和 44%，分别占研究队列中患者的 12%和 10%。5 名患者存在 2 个 PV，11 个 PV 是新的。最常见的 PV 存在于 BRCA1（n：18）、BRCA2（n：19）、ATM（n：7）、CHEK2（n：7）和 TP53（n：5）基因中。三阴性肿瘤患者中有 31%和激素受体阳性肿瘤患者中有 25%的患者有 panel 检测到 PV/LPVs。具有 PV 的患者中，一级亲属的家族史（p=0.029）、符合 NCCN 标准的数量（p=0.036）和腋窝淋巴结受累（p=0.000）更为常见。当与仅进行 BRCA1 和 2 基因检测的患者组（n=106）结合时，土耳其≤40 岁的乳腺癌患者中有 16%的患者在 BRCA 基因中存在 PVs。
土耳其≤40 岁的乳腺癌患者中有五分之一的患者在 26 基因遗传性癌症 panel 中至少存在一个乳腺癌易感基因的 PV/LPV。与激素受体和 Her-2 阳性亚型相比，三阴性年轻发病患者的 PV/LPV 频率更高。我们在年轻发病乳腺癌患者中 BRCA1/2 和非 BRCA 基因中发现的 PV/LPV 频率与文献一致。
