Kostiuchenko Y. Hereditary breast cancer surgical treatment

Breast cancer (BC) is the most common malignant neoplasm among women in Ukraine and the world. About 2.2 million new cases of this disease are diagnosed every year, and the incidence is increasing. Of course, the goal of scientists and clinicians is to find opportunities to reduce morbidity, improve early diagnosis and treatment outcomes. The genetic factor is extremely important, as it is not subject to modification (with the exception of modern possibilities of preimplantation genetic diagnostics during pregnancy planning) and gives the highest risks of cancer. The relevance of the work is due to the significant contribution of pathogenic variants (PVs) of genes of hereditary BC in increasing the risk of occurrence of BC, often of more aggressive types and at an earlier age. Genetic testing and choosing the right strategy for patients with detected PVs is important both to reduce the incidence and to improve the rates of early diagnostics and treatment outcomes for a significant proportion of BC patients. The main goal of the PhD paper is to improve the immediate and long-term results of surgical treatment of hereditary BC patients. Research objectives: 1. To study the prevalence and variability of gene variants of hereditary BC in Ukraine by the next generation DNA sequencing (NGS) method among BC patients with risk factors for heredity of the disease according to the NCCN. 2. To investigate the role of the result of genetic testing among other factors in choosing the scope of surgical treatment for BC patients. 3. To compare the results of surgical treatment of BC patients, in particular breast conserving surgery (BCS) and bilateral subcutaneous mastectomy (BSM) (due to the presence of PVs of hereditary BC), according to indicators of quality of life, the number of complications and repeated operations, the level of patient satisfaction with the selected amount of surgery, and the level of relapses. 4. As an alternative to surgical tactics, to investigate the effectiveness of endocrinological prophylaxis of BC with tamoxifen, taking into account the phenotype of the CYP2D6 gene for healthy carriers of PVs. 5. Develop and optimize recommendations for the selection of the scope of surgical treatment for hereditary BC patients and preventive tactics for healthy carriers of PVs. Results and discussion. Prevalence and variability of gene variants of hereditary BC in Ukraine, determined by NGS panel testing among BC patients with hereditary risk factors according to NCCN, are shown. Among 160 studied patients, 90 variants were found in 72 patients (45%). Among them, 59 patients (81.9%) had one variant, 13 patients (18.1%) had more than one variant.