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 BRCA status and genomic scar score (GSS), was analyzed in 452 ovarian cancer specimens. The successful rate of HRD testing was 86% (388/452). The BRCA 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 BRCA mutation frequency. The most substantial contribution to HRD level diversity is testing criteria depending on intrahospital arrangements. The analysis shows that biallelic BRCA 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.

This paper introduces the reader to the field of liquid biopsies and cell-free nucleic acids, focusing on circulating tumor DNA (ctDNA) in breast cancer (BC). BC is the most common type of cancer in women, and progress with regard to treatment has been made in recent years. Despite this, there remain a number of unresolved issues in the treatment of BC; in particular, early detection and diagnosis, reliable markers of response to treatment and for the prediction of recurrence and metastasis, especially for unfavorable subtypes, are needed. It is also important to identify biomarkers for the assessment of drug resistance and for disease monitoring. Our work is devoted to ctDNA, which may be such a marker. Here, we describe its main characteristics and potential applications in clinical oncology. This review considers the results of studies devoted to the analysis of the prognostic and predictive roles of various methods for the determination of ctDNA in BC patients. Currently known epigenetic changes in ctDNA with clinical significance are reviewed. The possibility of using ctDNA as a predictive and prognostic marker for monitoring BC and predicting the recurrence and metastasis of cancer is also discussed, which may become an important part of a precision approach to the treatment of BC.

Homologous recombination repair deficiency (HRD) is involved in the development of high-grade serous ovarian carcinoma (HGSOC) and its elevated sensitivity to platinum-based chemotherapy. To investigate the heterogeneity of the HRD-positive HGSOC we evaluated the HRD status, including BRCA mutations, genomic scar score, and methylation status of BRCA1/2 genes in 352 HGSOC specimens. We then divided the HRD-positive cohort into three molecular subgroups, the BRCA mutation cohort (BRCA+), BRCA1 methylation cohort (Meth+), and the rest of the HRD+ cohort (HRD+BRCA-Meth-), and evaluated their first-line chemotherapy response, benefit from olaparib, and progression-free survival (PFS). HRD-positive status was detected in 65% (228/352) of samples. The first group, BRCA+, accounted for 45% (102/228) of HRD positive cases and showed the best outcome in platinum therapy (ORR 96%), the highest olaparib benefit (p = 0.006) and the highest median PFS (46 months). The frequency of the second cohort, Meth+, among HRD-positive patients was 23% (52/228). Patients with Meth+ HGSOC showed a significantly poorer outcome, with a median PFS of 19 months, a significantly lower ORR to platinum therapy (84%) and a modest, but not significant, benefit from olaparib maintenance. The third HRD+BRCA-Meth- group accounted for 32% (74/228) of HRD-positive patients and showed an ORR to platinum therapy similar to that of the BRCA+ group (90%), a higher, but not statistically significant, benefit from olaparib and a median PFS of 23 months. In conclusion, Meth+ subgroup had poor outcomes in terms of chemotherapy response, olaparib benefit, and PFS compared to the other HRD+ subgroups, requiring a more thorough follow-up.

The HALO study (NCT04991051) determined the prevalence of homologous recombination deficiency and its associated factors in patients with high-grade serous/endometrioid ovarian, primary peritoneal, and/or fallopian tube cancers across Asia, the Middle East, and Russia. This multinational, cross-sectional, real-world study enrolled adult women with newly diagnosed stage III or IV high-grade serous/endometrioid ovarian, primary peritoneal, and/or fallopian tube cancers. Formalin-fixed paraffin-embedded tumor blocks were collected within 120 days of enrollment. The prevalence of homologous recombination deficiency, high genomic instability score (GIS) without tumor BRCA mutations, and BRCA mutations were evaluated along with patient characteristics. Factors associated with homologous recombination deficiency, high GIS without BRCA mutations, and BRCA mutations were identified using a logistic-regression model. Of the 734 patients (median [range] age; 59.0 [23.0-89.0] years), most (92.9%) had a primary ovarian tumor, followed by primary peritoneal (4.1%) and fallopian tube cancers (3.0%). Of the tested 662 patients; 56.0% (371) were homologous recombination deficiency-positive (Asia, 52.0%; the Middle East, 52.2%; Russia, 58.5%). Overall, 204 (30.8%) patients had a high GIS without BRCA mutations (Middle East, 23.9%; Russia, 31.9%; Asia, 41.3%), and 167 (25.2%) had BRCA mutations (Asia, 10.7%; Russia, 26.6%; Middle East, 28.3%). Patients with 1 comorbidity versus no comorbidities (96 vs 207, OR 1.54), a family history of genetically-related cancers versus no family history of cancer (82 vs 224, OR 2.64), and contraceptive use versus no history of contraceptive use (47 vs 323, OR 2.04) were more likely to have homologous recombination deficiency. This real-world study reported a homologous recombination deficiency prevalence of 56.0% (ranging from 52.0% to 58.5%) across Asia, the Middle East, and Russia. Our results highlight the unmet need to implement guideline-recommended testing and real-world data collection for all patients newly diagnosed with advanced high-grade epithelial ovarian cancer to optimize treatment strategies.

Ovarian cancer (OC) is the most lethal gynecological cancer worldwide. DNA damage plays an important role in cancer development, and the proteins encoded by XRCC1 and ERCC2 are important components of the DNA repair system. This study aimed to examine the relationship between the rs25487 XRCC1 and rs13181 ERCC2 polymorphisms and the risk of OC development in women from the Moscow region. DNA was isolated from the blood of 129 healthy donors and tissues and blood samples from 125 patients with OC and studied using real-time PCR. An increase in odds ratios (OR) was obtained for OC tissue and blood for both T (OR = 1.46, 95% confidence interval [CI] = 1.22–1.76, P = 0.00005), and for T/T of rs25487 XRCC1. The most significant OR values were found for the T/T genotype using the codominant model (OR = 2.11, 95% CI = 1.44–3.07, P = 0.00006) and dominant model (OR = 3.13, 95% CI = 1.44–6.79, P = 0.0025) for the pooled blood and tissue groups. For rs13181 ERCC2, differences were observed for the T/G genotype in OC tissues (OR = 0.69, 95% CI = 0.51–0.92, P = 0.011) in the codominant model. In this study, the association of allele T and genotypes of rs25487 XRCC1 and T/G of rs13181 ERCC2 with OC was shown. Our results indicate that these polymorphisms may be involved in the pathogenesis of OC and are promising for further studies on therapeutic applications in OC.

Given the high rate of recurrence of ovarian cancer, the search for new therapeutic strategies are topical issue. According to various studies the effectiveness of drug treatment relapse depends on the platinum-free interval, increasing in proportion to its duration. If therapy is platinum-resistant recurrent ovarian cancer is a standard approach, the treatment of platinum-sensitive recurrent algorithm is not fully defined. Comparison of platinum and non-platinum combinations revealed the advantage of combined platinum- treatment for patients with platinum-free interval of more than 6 months without an increase in life expectancy. Non-platinum combination of trabectedin with pegylated liposomal doxorubicin has shown comparable efficacy with an advantage in overall survival in patients with platinum-free interval of 6–12 months. A platinum-free interval prolongation by the use of non-platinum mode increases the efficiency of subsequent platinum-based therapy, increasing the life expectancy of patients . Currently under study molecular markers and prognostic factors allowing to define a group of patients who have the greatest benefit from the use trabectedin with pegylated liposomal doxorubicin as second-line chemotherapy.