目的:本研究旨在提供前列腺癌中BRCA1/2和HRR基因突变患病率的实际数据。
方法:我们收集了197例原发性和转移性前列腺癌的测序数据,其中HRR突变分析是在过去5年内根据临床要求进行的.所有病例均使用靶向NGSBRCAness多基因小组进行分析,包括8个HRR基因(ATM,BRCA1,BRCA2,CDK12,CHEK2,FANCA,HDAC2,PALB2)。
结果:我们的研究结果表明,根据FDA标准,潜在的可靶向突变的患病率为20.8%,这与文献相当。然而,我们队列中可靶向BRCA2突变的频率低于mCRPC的报告,ATM和CHEK2突变反而更普遍.因此,根据FDA批准,20.8%(n=38)的病例符合奥拉帕尼治疗标准,只有4.9%(n=9)符合EMA批准的资格标准。
结论:这项研究为BRCA1/2和HRR基因突变的前景以及前列腺癌中HRR基因检测的实际临床管理提供了有价值的现实世界见解。有助于更好地了解患者接受PARPi治疗的资格。
OBJECTIVE: This study seeks to contribute real-world data on the prevalence of BRCA1/2 and HRR gene mutations in prostate cancer.
METHODS: We compiled sequencing data of 197 cases of primary and metastatic prostate cancer, in which HRR mutation analysis was performed upon clinical request within the last 5 years. All cases were analyzed using a targeted NGS BRCAness multigene panel, including 8 HRR genes (ATM, BRCA1, BRCA2, CDK12, CHEK2, FANCA, HDAC2, PALB2).
RESULTS: Our findings reveal a prevalence of potentially targetable mutations based on FDA criteria of 20.8%, which is comparable to the literature. However, the frequency of targetable BRCA2 mutations within our cohort was lower than reported for mCRPC and ATM and CHEK2 mutations were more prevalent instead. Thus, while 20.8% (n = 38) of the cases meet the criteria for olaparib treatment per FDA approval, only 4.9% (n = 9) align with the eligibility criteria according to the EMA approval.
CONCLUSIONS: This study offers valuable real-world insights into the landscape of BRCA1/2 and HRR gene mutations and the practical clinical management of HRR gene testing in prostate cancer, contributing to a better understanding of patient eligibility for PARPi treatment.