BRCA-like phenotype in determining the treatment tactics for patients with breast cancer.

Abstract

Introduction. Currently, the issue of chemo-induced resistance and restoration of homologous recombination gene activity in the treatment of patients with breast cancer (BC) remains open. Aim: to study the relationship between homologous recombination deficiency (HRD) and the effectiveness of treatment and to assess the compensability of the BRCA-like phenotype under the influence of chemotherapy drugs. Methods. The study included 130 patients with BC. For in vitro studies, the following breast cancer cell lines were used: MCF-7, MDA-MB-231, MDA-MB-468. The analysis of HRD parameters was performed using: microarray analysis, RT-PCR and NGS. Results. Hyperexpression of CHEK1, PARP1, BRCA1 is associated with tumor progression, as well as the appearance of amplifications in the BRCA1, BARD1, CHEK1 genes and others (83% of cases). Work on in vitro models made it possible to establish that under the influence of chemotherapy drugs, the state of the homologous recombination system is restored, and this may be one of the reasons for the formation of tumor cell resistance. Conclusions. The presence of HRD in a breast tumor is an important marker in a personalized approach to treatment. However, the question of overcoming the formation of tumor resistance due to HRD compensatory remains open, which undoubtedly requires further study.