The polymorphic markers of the XRCC1, ERCC5, TP53, CDKN1A1 genes and the survival of triple negative breast cancer patients after platinum-based chemotherapy.
Authors: Kolyadina Irina Vladimirovna , Zavarykina Tatiana , Lomskova Polina , Gordeeva Olga , Kapralova Maria , Ganshina Inna , Khokhlova Svetlana Victorovna 
Published: June 2023

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.