乳腺癌（BC）中BRCA缺陷型癌细胞对铂类化疗和PARP抑制剂具有高度敏感性，原因在于它们在同源重组（HR）途径上的缺陷。然而，HR缺陷（HRD）不仅限于与BRCA相关的BC，这突显了以其他方式富集HRD肿瘤的需求。一种有希望的方法是使用功能性HRD测试，通过测量DNA损伤位点上RAD51蛋白的累积来评估肿瘤细胞的HR能力。本研究旨在评估基于RAD51的功能性HRD测试用于鉴定HRD BC的性能。将63个经诊断的福尔马林固定石蜡嵌埋（FFPE）BC样本的功能性HR状态通过应用RAD51-FFPE测试来确定。对样本进行筛查，检测HR的（表观）遗传缺陷以及匹配的肿瘤样本使用RECAP测试进行分析，RECAP测试需要在体外照射鲜活肿瘤组织，前提是RECAP测试确定的HRD状态忠实地代表了功能性HR状态。RAD51-FFPE测试将23个（37％）肿瘤识别为HRD，其中包括3个BRCA1/2的致病变异体。RAD51-FFPE测试在确定HR类别时表现出88％的敏感性和76％的特异性，与RECAP测试所定义的HR类别相吻合。鉴于其高敏感性和与FFPE样本的兼容性，RAD51-FFPE测试具有富集HRD肿瘤的巨大潜力，包括与BRCA缺陷相关的肿瘤。这个潜力可扩展到在常规临床实践中DNA测试可能具有挑战性或难以获得的情况。考虑到治疗决策和患者分层的潜在影响，这一点尤为重要。 © 2023. 作者(们)。

BRCA-deficient breast cancers (BC) are highly sensitive to platinum-based chemotherapy and PARP inhibitors due to their deficiency in the homologous recombination (HR) pathway. However, HR deficiency (HRD) extends beyond BRCA-associated BC, highlighting the need for a sensitive method to enrich for HRD tumors in an alternative way. A promising approach is the use of functional HRD tests which evaluate the HR capability of tumor cells by measuring RAD51 protein accumulation at DNA damage sites. This study aims to evaluate the performance of a functional RAD51-based HRD test for the identification of HRD BC.The functional HR status of 63 diagnostic formalin-fixed paraffin-embedded (FFPE) BC samples was determined by applying the RAD51-FFPE test. Samples were screened for the presence of (epi)genetic defects in HR and matching tumor samples were analyzed with the RECAP test, which requires ex vivo irradiated fresh tumor tissue on the premise that the HRD status as determined by the RECAP test faithfully represented the functional HR status.The RAD51-FFPE test identified 23 (37%) of the tumors as HRD, including three tumors with pathogenic variants in BRCA1/2. The RAD51-FFPE test showed a sensitivity of 88% and a specificity of 76% in determining the HR-class as defined by the RECAP test.Given its high sensitivity and compatibility with FFPE samples, the RAD51-FFPE test holds great potential to enrich for HRD tumors, including those associated with BRCA-deficiency. This potential extends to situations where DNA-based testing may be challenging or not easily accessible in routine clinical practice. This is particularly important considering the potential implications for treatment decisions and patient stratification.© 2023. The Author(s).