Own Experience of Using Next-Generation Sequencing in the Diagnosis of BRCA-Associated Breast Cancer

Introduction. Breast cancer systematically occupies a leading place among cancer incidence in Russia. Moreover, hereditary forms of tumors occur in 2–8 % of patients. Almost 30 % are associated with pathogenic variants in the BRCA1/2 genes. Since the beginning of 2023, patients with BRCA-associated breast cancer at the Sverdlovsk Regional Oncology Center have been examined using next-generation (NGS) sequencing to carry out the necessary preventive, diagnostic and treating measures.

The purpose of the study was to evaluate the effectiveness of next-generation sequencing in comparison with polymerase chain reaction (PCR) tests and to assess the relevance of the existing PCR panel.

Materials and methods. This work is based on an analysis of the results of molecular genetic testing of 132 breast cancer patients aged 29 to 66 years. Firstly, the biological material of all patients was tested using the polymerase chain reaction in real time method to search for frequent pathogenic variants. If the result was negative, patients were referred for a study using next-generation sequencing to look for rare variants.

Results and discussions. A study of common pathogenic variants of the BRCA1/2 genes using real-time PCR showed the presence of “founder mutations” in 3.0 % of patients. The search for rare pathogenic germline variants using NGS made it possible to identify pathogenic gene variants in another 25 patients (18.9 % of examined).

Conclusion. Taking into account the more aggressive course of hereditary forms of breast cancer, the early age of manifestation of the disease, a lot of rare mutations in the Sverdlovsk region and high probability of transmitting them to children, it is necessary to develop follow-up programs of relatives for the purpose of timely diagnosis and treatment.

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