Hepatocellular carcinoma (HCC) or liver cancer is the most common primary malignant tumor of the liver, which is characterized on the first place by a poor prognosis. HCC was diagnosed in 92 patients (62.6%) in 2019 and the period from January to April 2020 in the Republic of Bashkortostan, and among them, 68.47% had stage IV cancer. International professional guidelines suggest screening for early HCC detection. Systemic drug therapy is the treatment of choice for inoperable HCC according to professional guidelines. Inhibition of the VEGF pathway is one of the current methods of therapy for advanced HCC. Lenvatinib is a tyrosine kinase inhibitor for the treatment of advanced HCC that is not subject to local interventions. This article provides a description of a clinical case of successful treatment of a 67-year-old patient with advanced hepatocellular carcinoma. He was appointed for targeted therapy with lenvatinib for HCC that was not subject to local interventions, which led to long-term stabilization. There was a positive trend in the patients condition from the first weeks of therapy. The working capacity was restored. The therapy showed a satisfactory tolerability profile.

Background. By 2020, breast cancer (BC) has become the most frequent malignancy in the world. The most common type of BC is HR+/HER2-negative cancer,2540% of which harbors PIK3CA mutations that affect the catalytic subunit of the PI3K protein. PIK3CA alterations are actionable, as such neoplasms can be treated with a combination of fulvestrant and the PI3K inhibitor alpelisib. As PIK3CA mutations have an extremely versatile effect on the characteristics of a tumor cell, numerous associations of PIK3CA mutations and various clinico-pathological characteristics of BC can be traced. Aim. Our aim was to clarify the information on the frequency and spectrum of PIK3CA mutations in Russian patients with HR+/HER2- advanced BC, and to study the association of PIK3CA mutations with clinical and pathological parameters of BC. Materials and methods. Tissue samples from 694 patients with HR+/HER2- advanced BC (mixed population of primary metastatic and relapsed tumors) who received any line of anti-cancer treatment in Dec 2020 to June 2021 in Russian Federation were analyzed by high-resolution melting, allele-specific PCR, digital droplet PCR and Sanger sequencing (exons 7,9, and 20 of the PIK3CA gene). Mutation rates in different BC subgroups were compared using the Fishers exact test. The age at diagnosis in patients with different PIK3CA status was compared using the MannWhitney U-test. The relationship between the PIK3CA status and the degree of tumor differentiation was compared using the CochraneArmitage test for trends. Luminal A and B BC expression subtypes were distinguished with surrogate IHC markers according to St.-Gallen recommendations (2013). Results. Mutations were identified in 220/694 (32%) BC patients. The three most frequent missense substitutions in the PIK3CA gene (p.E542K, p.E545K, and p.H1047R) accounted for 190/220 (86%) mutations. Associations of PIK3CA mutations with luminal A subtype of BC, low proliferation index, small size of the primary tumor, and absence of signs of hereditary cancer were revealed. Associations of mutations in the kinase domain of PIK3CA (p.H1047R) with late recurrence of locally advanced BC and with non-Slavic ethnic origin of patients were found. Conclusion. PIK3CA mutation rate of 32% confirms high prevalence of mutation in Russian population, with some differences reflecting the ethnic origin of patients.

Профилактика злокачественных новообразований у здорового населения на данный момент является при оритетной задачей здравоохранения. Программы массового скрининга и генетическое консультирование на селения помогают выявить не только предраковые состояния, но и наследственную предрасположенность к возникновению опухолевых заболеваний. Большинство наследственных раковых заболеваний передается по аутосомнодоминантному типу. Своевременный скрининг у здоровых лиц -носителей мутированных генов позволяет выработать персонифицированный подход к мерам профилактики. Наличие у близких родственни ков рака молочной железы и/или яичников всегда рассматривается как возможность раннего выявления нали чия генетических мутаций у здорового пациента, как женщины, так и мужчины. Наличие у близких родствен ников рака молочной железы и/или яичников, рака предстательной железы существенно увеличивает шансы определения у пробанда герминативной мутации в генах BRCA1 и BRCA2. Гены, связанные с повышенным ри ском развития рака поджелудочной железы, -BRCA1, BRCA2, CDKN2A, PALB2, PRSS1, STK11. Наиболее частые синдромы генетических мутаций, приводящих к предрасположенности и развитию опухолевых заболеваний: синдром наследственного рака молочной железы и яичников, синдром Линча, семейный аденоматозный по липоз, синдром Пейтца -Егерса и синдром Ли -Фраумени, синдром множественной эндокринной неоплазии. Ключевые слова: злокачественные новообразования, профилактика, генетическая предрасположенность к бо лезни, генетическое тестирование, мутагенности тесты, гены EGFR, гены BRCA1, гены BRCA 2, гены TP53, гены RET, микросателлитная нестабильность Для цитирования: Липатов О.Н., Ахметгареева К.Т. Роль генетических мутаций в профилактике злокачественных новообразований у здорового населения (обзор литературы). Креативная хирургия и онкология. 2020;10(4):330-338.