HRD Testing of Ovarian Cancer in Routine Practice: What Are We Dealing With?

Assessment of homologous recombination deficiency (HRD) status is now essential for ovarian cancer patient management. The aim of our study was to analyze the influence of ethnic variations, tumor purity, and neoadjuvant chemotherapy (CT) on the determination of HRD scores as well as to evaluate fea...

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Main Authors: Tatiana Kekeeva, Yulia Andreeva, Alexander Tanas, Alexey Kalinkin, Svetlana Khokhlova, Tatiana Tikhomirova, Alexandra Tyulyandina, Anatoly Popov, Maria Kuzmenko, Mikhail Volkonsky, Natalia Chernorubashkina, Valeria Saevets, Vadim Dmitriev, Valentina Nechushkina, Olga Vedrova, Sergei Andreev, Sergey Kutsev, Vladimir Strelnikov
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/13/10497
Description
Summary:Assessment of homologous recombination deficiency (HRD) status is now essential for ovarian cancer patient management. The aim of our study was to analyze the influence of ethnic variations, tumor purity, and neoadjuvant chemotherapy (CT) on the determination of HRD scores as well as to evaluate feasibility of HRD testing with the Amoy HRD Focus Assay in routine clinical practice. The HRD status, including the <i>BRCA</i> status and genomic scar score (GSS), was analyzed in 452 ovarian cancer specimens. The successful rate of HRD testing was 86% (388/452). The <i>BRCA</i> mutational rate was 29% (114/388); 252 samples (65%) were classified as HRD-positive. Our data demonstrate the feasibility of internal HRD testing by the AmoyDx HRD Focus Panel for high-grade serous ovarian cancer (HGSOC), showing results similar to other methods. The HRD rate in the Russian population is very similar to those of other European populations, as is the <i>BRCA</i> mutation frequency. The most substantial contribution to HRD level diversity is testing criteria depending on intrahospital arrangements. The analysis shows that biallelic <i>BRCA</i> alterations had higher GSS compared with those with monoallelic inactivation, consistent with positive HRD status. The study indicates that grades 1–2 of the pathological response caused by chemotherapy affect HRD scores and suggests controlling for tumor purity of 40% or more as a critical factor for GSS measurement.
ISSN:1661-6596
1422-0067