Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
Liufeng Yang , Yuanyue Li , Qian Hu , Tingting Zhang , Mengyue Cui , Jie Zhang
Background: PARP inhibitors (PARPi) have shown significant clinical benefit as maintenance or systematic therapy in patients with ovarian cancer (OC) with BRCA1/2 mutation or positive homologous-recombination deficiency (HRD) status. However, patients with BRCA1/2 mutation not only showed better efficiency of PARPi, but also higher HRD score than other populations. Therefore, patients with BRCA1/2 mutation have received much attention. However, there are many kinds of variants in BRCA1/2 of OC patients. The purpose of this study is to explore the distribution of BRCA1/2 copy number variation (CNV) in OC patients and its association with HRD score. Methods: A cross-sectional analysis of 1636 OC patient who were retrospectively analyzed with a customized 3D-HRD panel (panel of Next-generation sequencing) between 2020 and 2022 was carried out. The HRD score was calculated as the sum of the LOH, TAI, and LST and we defined HRD score more than 30 and deleterious BRCA1/2 mutation as HRD positivity. Results: In this cohort (n = 1636), we divided the patients into 4 groups according to the BRCA1/2 status. Group1: patients with BRCA1/2 SNV (single-nucleotide variation) combined with CNV (n = 45); Group2: patient with BRCA1/2 CNV (n = 155); Group3: patient with BRCA1/2 SNV (N = 308); Group4: patient with BRCA1/2 WT (wild type, n = 1128). HRD scores decreased significantly from Group1 to Group4. And the proportion of HRD positive patients decreased significantly from Group1 to Group4. Conclusions: Different BRCA1/2 statuses lead to different HRD characterization in OC patients. OC patients with BRCA1/2 CNV (with/without BRCA1/2 SNV) showed higher HRD score than patients with BRCA1/2 SNV. These patients may deserve opportunity for PARPi treatment besides patients with germline or somatic BRCA1/2 mutation, especially for PARPi with specific requirements for patients, such as Olaparib.
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