文章：

对极早发性乳腺癌（≤30岁）患者进行基因检测，发现其生殖系致病性变异率较高，主要集中于BRCA1、TP53及BRCA2基因。

Genetic Testing of Breast Cancer Patients with Very Early-Onset Breast Cancer (≤30 Years) Yields a High Rate of Germline Pathogenic Variants, Mainly in the BRCA1, TP53, and BRCA2 Genes

原文发布日期：27 June 2024

DOI: 10.3390/cancers16132368

类型: Article

开放获取: 是

英文摘要：

Early-onset breast cancer constitutes a major criterion for genetic testing referral. Nevertheless, studies focusing on breast cancer patients (≤30 years) are limited. We investigated the contribution and spectrum of known breast-cancer-associated genes in 267 Greek women with breast cancer ≤30 years while monitoring their clinicopathological characteristics and outcomes. In this cohort, a significant proportion (39.7%) carried germline pathogenic variants (PVs) distributed in 8 genes. The majority, namely 36.7%, involvedBRCA1,TP53,andBRCA2. PVs inBRCA1were the most prevalent (28.1%), followed byTP53(4.5%) and BRCA2 (4.1%) PVs. The contribution of PVs inCHEK2,ATM,PALB2,PTEN, andRAD51Cwas limited to 3%. In the patient group ≤26 years,TP53PVs were significantly higher compared to the group 26–30 years (p= 0.0023). A total of 74.8% ofTP53carriers did not report a family history of cancer. Carriers of PVs receiving neoadjuvant chemotherapy showed an improved event-free survival (p< 0.0001) compared to non-carriers. Overall, many women with early-onset breast cancer carry clinically actionable variants, mainly in theBRCA1/2andTP53genes. The inclusion of timely testing ofTP53in these patients provides essential information for appropriate clinical management. This is important for countries where reimbursement involves the cost of genetic analysis ofBRCA1/2only.

摘要翻译： 

早发性乳腺癌是转诊进行基因检测的主要指征。然而，针对年轻乳腺癌患者（≤30岁）的研究仍较为有限。本研究对267名年龄≤30岁的希腊女性乳腺癌患者进行了调查，分析了已知乳腺癌相关基因的致病性变异分布及其贡献，同时监测了其临床病理特征与预后。在该队列中，有相当大比例（39.7%）的患者携带种系致病性变异，这些变异分布于8个基因。其中绝大多数（36.7%）涉及BRCA1、TP53和BRCA2基因。BRCA1基因的致病性变异最为常见（28.1%），其次是TP53（4.5%）和BRCA2（4.1%）基因的变异。CHEK2、ATM、PALB2、PTEN和RAD51C基因的致病性变异贡献率合计仅为3%。在≤26岁的患者组中，TP53基因致病性变异的发生率显著高于26-30岁组（p=0.0023）。值得注意的是，74.8%的TP53基因变异携带者无癌症家族史。与非携带者相比，接受新辅助化疗的致病性变异携带者显示出更优的无事件生存期（p<0.0001）。总体而言，许多早发性乳腺癌患者携带具有临床指导意义的基因变异，主要集中在BRCA1/2和TP53基因。对这些患者及时进行TP53基因检测可为临床管理提供关键信息，这对于那些仅报销BRCA1/2基因检测费用的国家尤为重要。

原文链接：

Genetic Testing of Breast Cancer Patients with Very Early-Onset Breast Cancer (≤30 Years) Yields a High Rate of Germline Pathogenic Variants, Mainly in the BRCA1, TP53, and BRCA2 Genes