Background. Breast cancer is the most common cancer among women. Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, in which there are no special targets for therapy. Therefore chemotherapy is still leading treatment for TNBC including the regiments with platinum drugs.Aim. To study the association of polymorphic markers of the genes XRCC1 (rs25487), ERCC5 (rs17655), TP53 (rs1042522), CDKN1A1 (rs1801270) with progression-free survival (PFS) and overall survival (OS) of TNBC patients after platinum-based neoadjuvant chemotherapy.Materials and methods. Polymorphic markers of the XRCC1, ERCC5, CDKN1A and TP53 genes were studied in blood samples of 67 patients with stage II–III TNBC by real-time polymerase chain reaction with fluorescent allele-specific probes. The results of determining the markers were compared with PFS and OS using the Kaplan–Meyer method and the log-rank-test.Results. The association was found for the polymorphic marker rs25487 of the XRCC1 gene with PFS (carrying the T/T genotype was associated with a decrease of median PFS: 15.6 months versus 34.3 months, p = 0.013) and OS (carrying the T allele was associated with a decrease of median OS: 24.3 months versus 34.6 months, p = 0.041) without depending on the BRCA status. For the polymorphic marker rs17655 of the ERCC5 gene, significant difference in PFS was obtained in the period from 15.4 to 60.0 months of follow-up (the carrier of the C allele was associated with a decrease of median PFS: 20.0 months versus 35.2 months, p = 0.035). When considering the genotypes of the polymorphic marker of the ERCC5 gene differences were revealed between patients with the C/C genotype (M = 15.9 months) and two other genotypes (M = 33.6 months), p = 0.039. For the polymorphic marker rs1801270 of the CDKN1A gene significant differences in PFS were obtained in the period from 15.4 to 60.0 months of follow-up (for carriers of allele A, a decrease in median PFS was observed: 16.6 months versus 32.0 months, p = 0.046). For the polymorphic marker of the TP53 gene (rs1042522) a tendency to decrease OS for carriers of the C/C genotype was found seems promising for further study.Conclusion. The association of the studied polymorphic markers of the genes XRCC1 (rs25487), ERCC5 (rs17655) and CDKN1A (rs1801270) with PFS was revealed in patients with TNBC. Association with OS was obtained for the polymorphic marker of the XRCC1 gene (rs25487). These data may allow for further validation to individualize the treatment of this category of patients.
e12556 Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. There are no special targets for neoadjuvant therapy of TNBC, and leading treatment for TNBC is chemotherapy including the regiments with platinum drugs. The aim of the work was to study the relationship between the polymorphic markers rs25487 of the XRCC1 gene, rs17655 of the ERCC5 gene, rs1042522 of the TP53 gene, rs1801270 of the CDKN1A1 gene with progression-free (PFS) and overall survival (OS) in patients with TNBC after platinum-based neoadjuvant chemotherapy. Methods: The work includes 67 TNBC patients with II-III stage of disease. The samples of blood of patients were collected before chemotherapy. All patients received platinum-based neoadjuvant chemotherapy (docetaxel or paclitaxel in combination with carboplatin/cisplatin). Data on the carriage of mutations in the BRCA 1/2 genes were obtained from medical institutions. DNA was isolated from samples of blood and polymorphic markers of the XRCC1, ERCC5, CDKN1A and TP53 genes were analyzed by real-time PCR with fluorescent allele-specific probes on CFX96 (Bio-Rad). The results were compared the clinical data (PFS and OS) using the Kaplan-Meyer method and the log-rank test. Results: The median follow-up time was 27.6 (minimum 6.4 – maximum 66.9) months. There was an association between carrying the T/T genotype of the polymorphic marker rs25487 of the XRCC1 gene and a decrease of median PFS (15.6 months versus 34.3 months, p = 0.013). The carriage of T allele of this marker was associated with a decrease of median OS (24.3 months versus 34.6 months, p = 0.041). These relationships for the XRCC1 marker were observed without depending on the BRCA status. Significant difference in PFS was obtained for the polymorphic marker rs17655 of the ERCC5 gene in the period from 15.0 to 60.0 months of follow-up. The decrease of median PFS was observed in carriers of the C allele (20.0 months versus 35.2 months, p = 0.035). The differences were more pronounced for carriers of the C/C genotype: the median PFS for carriers of C/C and two other genotypes was 15.9 and 33.6 months, respectively ( p = 0.039). A decrease in median PFS was observed for carriers of allele A of the polymorphic marker rs1801270 of the CDKN1A gene in the period from 15.0 to 60.0 months of follow-up: 16.6 months versus 32.0 months, p = 0.046. A tendency to decrease OS for carriers of the C/C genotype of the polymorphic marker rs1042522 of the TP53 gene was found. Conclusions: We revealed a relationship between the polymorphic markers rs25487 of the XRCC1 gene, rs17655 of the ERCC5 gene, and rs1801270 of the CDKN1A1 gene with PFS in patients with TNBC, as well as a relationship between the polymorphic marker rs25487 of the XRCC1 gene and OS. These data need further validation and may allow individualizing the treatment of patients with TNBC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.