PDF(Pubmed)
Abstract：
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%, involved BRCA1, TP53, and BRCA2. PVs in BRCA1 were the most prevalent (28.1%), followed by TP53 (4.5%) and BRCA2 (4.1%) PVs. The contribution of PVs in CHEK2, ATM, PALB2, PTEN, and RAD51C was limited to 3%. In the patient group ≤26 years, TP53 PVs were significantly higher compared to the group 26-30 years (p = 0.0023). A total of 74.8% of TP53 carriers 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 the BRCA1/2 and TP53 genes. The inclusion of timely testing of TP53 in these patients provides essential information for appropriate clinical management. This is important for countries where reimbursement involves the cost of genetic analysis of BRCA1/2 only.
摘要：
早发性乳腺癌是基因检测转诊的主要标准。然而，针对乳腺癌患者(≤30年)的研究有限.我们调查了267名≤30岁的希腊乳腺癌女性中已知乳腺癌相关基因的贡献和光谱，同时监测其临床病理特征和结果。在这个队列中，很大一部分（39.7％）携带了分布在8个基因中的种系致病变异（PV）。大多数,即36.7%，涉及BRCA1、TP53和BRCA2。BRCA1中的PV最普遍(28.1%)，其次是TP53（4.5%）和BRCA2（4.1%）PVs。PVs在CHEK2、ATM、PALB2,PTEN,RAD51C限制为3%。在≤26岁的患者组中，TP53PV显著高于26-30岁组(p=0.0023)。共有74.8%的TP53携带者没有报告癌症家族史。与非携带者相比，接受新辅助化疗的PV携带者显示出改善的无事件生存率（p<0.0001）。总的来说,许多患有早发性乳腺癌的女性携带临床上可行的变异，主要在BRCA1/2和TP53基因中。在这些患者中纳入TP53的及时测试为适当的临床管理提供了必要的信息。这对于报销仅涉及BRCA1/2基因分析费用的国家很重要。
