早发性乳腺癌是基因检测转诊的一个主要标准。然而，针对乳腺癌患者（≤30 岁）的研究有限。我们调查了 267 名年龄≤30 岁患有乳腺癌的希腊女性中已知乳腺癌相关基因的贡献和谱，同时监测她们的临床病理特征和结果。在该队列中，很大一部分（39.7%）携带分布在 8 个基因中的种系致病变异 (PV)。大多数（36.7%）涉及 BRCA1、TP53 和 BRCA2。 BRCA1 中的 PV 最为常见 (28.1%)，其次是 TP53 (4.5%) 和 BRCA2 (4.1%) PV。 PV 在 CHEK2、ATM、PALB2、PTEN 和 RAD51C 中的贡献仅限于 3%。在≤26岁的患者组中，TP53 PV显着高于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 携带者表现出无事件生存期的改善 (p < 0.0001)。总体而言，许多患有早发性乳腺癌的女性携带临床上可操作的变异，主要是 BRCA1/2 和 TP53 基因。在这些患者中及时检测 TP53 为适当的临床管理提供了重要信息。这对于报销仅涉及 BRCA1/2 基因分析费用的国家来说非常重要。

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%, 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.