Relevance: Tamoxifen, which is widely used in the therapy of breast cancer (BC) is associated with an increased risk of endometrial cancer (EC). The tissue – specifi c agonistic effect of tamoxifen on the endometrium is well known, but the pathogenetic mechanisms underlying malignant transformation, remain poorly studied. Understanding these processes is crucial for devising strategies for the prevention and reduction of the risk of endometrial cancer (EC) in patients who receive tamoxifen.
Results: The review systematizes current data on the molecular mechanisms of tamoxifen effect on the endometrium. The genomic (classical and non-classical pathways of estrogen receptor activation) and non – genomic (GPER signaling cascades) mechanisms, as well as the role of tamoxifen metabolites in proliferation, angiogenesis, apoptosis, cell cycle regulation and DNA damage, along with therapeutic agents, involved in the pathogenesis of tamoxifen – associated endometrial cancer (EC) are examined.
Conclusion: The complexity and interconnected nature of pathogenesis of tamoxifen – induced endometrial cancer (EC) emphasizes the need for monitoring patients and developing safer methods of adjuvant therapy, that suppresses proliferative signaling pathways. Keywords: tamoxifen, endometrial cancer, GPER, estrogen receptors, pathogenesis
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Objective of the study is to highlight the dynamics of development and current concepts of sentinel lymph node biopsy techniques in endometrial cancer.
Materials and Methods. Analysis of scholarly articles presented in PubMed database, meta-analyses of foreign and Russian sources has been carried out.
Results. According to the novel molecular classifi cation, the role of sentinel lymph node biopsy in early stages of endometrial cancer may be questioned in the future, as information about the lymph node status in patients with POLE or p53 mutations does not change treatment strategy. Conversely, in patients with MMRd and NSMP mutations this technique should be widely adopted in combination with ultrastaging in order to determine indications for adjuvant therapy.
Conclusion. It is necessary to identify clear indications for sentinel lymph node biopsy in endometrial cancer, based on the tumor molecular status.
Keywords: endometrial cancer, sentinel lymph node biopsy, systematic lymphadenectomy, molecular classifi cation, surgi cal staging, ultrastaging
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Relevance: The anti-angiogenic drug bevacizumab is widely used in the treatment of ovarian cancer (OC). Various dosage regimens of bevacizumab (7.5 mg/kg or 15 mg/kg) may be used in the initial therapy of ovarian cancer (OC), however, the effi cacy of a reduced dose compared to the standard dose in ovarian cancer (OC) recurrences has been insuffi ciently studied.
Materials and Methods: A retrospective single-center study, which comprised patients with the fi rst recurrence of serous or endometrioid high-grade ovarian carcinoma who received second-line chemotherapy in combination with bevacizumab or without it for the period from 2014 to 2024, was conducted. To minimize systematic error, patient groups were balanced based on key prognostic factors (platinum-free interval, mutation status of BRCA, ECOG and etc.), and a propensity score matching (cardinality matching) method was used at a 1:1 ratio, patients were allocated into groups depending on whether they received bevacizumab or not. The effect of the bevacizumab dosing regimen on long-term outcomes was analyzed using Cox regression. The primary endpoint was progression-free survival (PFS), and the key secondary endpoint was overall survival (OS).
Results: A total of 635 patients were included in the analysis. After propensity score matching, the fi nal sample size was 354 patients (177 — bevacizumab, including 53 — 15 mg/kg; 177 — a control group). The median progression-free survival (PFS) in the bevacizumab group was 9.2 months versus 6.1 months in the control group (hazard ratio (HR) - 0.63; 95 % confi dence interval (CI) — 0.50-0.79; p < 0.001), and the median overall survival (OS) was 35.4 months and 22.0 months, respectively (hazard ratio (HR) - 0.55; 95 % confi dence interval (CI) — 0.42-0.73; p < 0.001). Multivariate analysis confi rmed the indepen dent contribution of bevacizumab in reducing the risk of progression (hazard ratio (HR) = 0.45; p < 0.001). No differences in effectiveness were observed between the 7.5 mg/kg and 15 mg/kg doses (hazard ratio (HR) = 0.95; p = 0.783).
Conclusions: The use of bevacizumab demonstrates effectiveness in ovarian cancer (OC) recurrences, with a reduced dose of bevacizumab (7.5 mg/kg) showing comparable effectiveness with the standard dose, signifi cantly improving long-term treatment outcomes. The results confi rm the use of low doses as a cost-effective feasible alternative without compromising treatment outcomes for patients.
Keywords: ovarian cancer, recurrence, chemotherapy, bevacizumab
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Objective of the study is to substantiate the relevance of search and study of early prognostic and diagnostic markers of ovarian cancer.
Materials and Methods. The review provides data of foreign and Russian scholarly articles of the subject published over the past 8 years in PubMed, Scopus and E-library.
Results. The analyzed literature data indicate that patients, especially those in the later stages, develop the immunosuppre ssive conditions, which are manifested in the inhibition of the function of effectors of antitumor immunity and in an enhancement of the suppressive effect due to an increase in subpopulations of T-regulatory cells and Th2 — helpers. Monocytes/ macrophages and myeloid dendritic cells, which produce infl ammatory mediators, stimulate angiogenesis and tumor cell proliferation, play an essential role in the development of immune dysfunction in ovarian cancer patients.
Conclusion. The identifi cation of parameters that allow to assess the systemic immune status and the intricacies of the immune microenvironment of the tumor, can be important for the clarifi cation of diagnosis, development of treatment strategy and of additional therapeutic strategies in ovarian cancer patients.
Keywords: ovarian cancer, antitumor immunity, cellular immunity, humoral immunity, ovarian cancer diagnosis, prognostic markers, tumor microenvironment
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Objective of the study is to carry out a systematic analysis of current publications on the epidemiology, molecular biology, clinical characteristics, and treatment strategies for borderline ovarian tumors (BOTs) to summarize current knowledge and identify areas for future research.
Materials and Methods. The review includes the data from Russian and foreign studies published in leading medical journals and databases, including PubMed, over the past 10 years. Particular emphasis was placed on epidemiological data, molecular mechanisms, surgical treatment options, and reproductive outcomes in patients with borderline ovarian tumors (BOTs).
Results. Epidemiological studies report that the incidence of borderline ovarian tumors (BOTs) is approximately 2.5 cases per 100,000 of women per year (US data), with the tumor structure and the incidence of various subtypes varying by region (e.g., in Denmark, the proportion of mucinous borderline ovarian tumors (BOTs) reaches 50 %, in Asia — up to 75.2 %).
Molecular mechanisms of borderline ovarian tumor (BOT) development are associated with mutations in the KRAS and BRAF genes, which contribute to the transition of benign mucinous cysts into borderline tumors and their subsequent trans formation into malignant neoplasms. Particular attention is paid to the morphological features of mucinous borderline ovarian tumor (MBOT), which includes a complex architectonics with epithelial proliferation and moderate cytologic atypia.
The clinical approach to treatment is determined based on the patient’s intention to preserve reproductive function. For patients who do not plan pregnancy, hysterectomy with bilateral salpingo — oophorectomy is recommended. For women planning pregnancy, organ-preserving surgeries are considered. Several promising studies, which highlighted the success of these organ-preserving strategies and demonstrated favorable outcomes, including the possibility of pregnancy after surgical treatment of borderline ovarian tumors (BOTs), have been conducted.
Consistent ultrasound examination to detect relapses, which would enable timely intervention in response to disease progression, is a crucial aspect of disease management and follow-up.
Conclusion. Current data certify signifi cant advances in understanding the pathogenesis and clinical management of borderline ovarian tumors (BOTs); however, further multicenter studies to investigate molecular mechanisms, optimize surgical techniques, and improve survival rates and reproductive health in women with borderline ovarian tumors, are required.
Keywords: borderline ovarian tumors, mucinous borderline ovarian tumor, KRAS, BRAF, molecular biology, organ-preser ving surgery, fertility preservation, recurrence
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Objective of the work is to investigate the epidemiological situation and the state of cervical cancer diagnostics in Voronezh region for the period 2019–2023, of cervical screening with an estimation of the rate of oncogenic high – risk human papil lomavirus (HPV) infection among the female population of Voronezh region. This includes evaluation of the effectiveness of cytological screening, as well as the prevalence of human papillomavirus (HPV) infection in women in Voronezh region.
Materials and Methods. Standardized statistical data on cervical cancer incidence and mortality in Voronezh region, in the Central Federal District and in the Russian Federation, as well as the data from Voronezh region’s cancer registry served as materials for this study. Statistical analysis was performed using the StatTech v. 4.7.2.
Results. The study revealed key trends in the epidemiology and prevention of cervical cancer in the Russian Federation. The decline in cervical cancer incidence by 2021 and its subsequent growth by 2023 indicate the need to analyze multifaceted factors, including accessibility to screening and the impact of post – pandemic processes. The expansion of human papillomavirus (HPV) screening coverage up to 63,36 % by 2024 is coupled with an increase in the proportion of positive results to 15,76 %, which refl ects enhanced diagnostic capabilities. The results of the study confi rm the need to improve the system of prevention and early diagnosis of cervical cancer, that require joint efforts of medical community, healthcare authorities and population. The elimination of cervical cancer remains a global priority in public healthcare, which is due to signifi cant rates of incidence and mortality among women of reproductive and working age.
Keywords: cervical cancer, cytological screening, HPV–testing, prevention
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Introduction. Vulvar melanoma is a rare disease that ranks second among all malignant vulvar neoplasms. Despite the visual accessibility of the tumor, the prognosis is adverse due to late diagnosis and inadequate approaches to therapy. Surgery is the main method of localized melanoma, while a combined approach including chemotherapy, radiation and immunotherapy is used for advanced forms of the disease. The number of publications on this topic is limited, which makes it relevant to systematize information on the etiopathogenesis, diagnosis and treatment of vulvar melanoma.
Objective is to summarize the literature data on the causes, methods of diagnosis and treatment of patients with vulvar melanoma.
Materials and Methods. The literature search was performed on PubMed, Elibrary, Scopus, CyberLeninka databases. The literature review included publications which contain modern aspects of the etiology, pathogenesis, diagnostic methods, surgical and drug treatment of the vulvar melanoma. 55 works were analyzed and 38 were selected for writing this review as the most relevant.
Conclusion. Vulvar melanoma is a highly aggressive disease. Surgical treatment of the initial stages remains the main one, but the technique of operations and indications for sentinel lymph node biopsy and lymph node dissection vary in different clinics. Treatment of advanced melanoma is based on the molecular biological features, including mutations in signaling pathways and PD-L1 expression in tumor cells. This leads to the development of new drug options and this requires extensive clinical studies to assess their safety and effi ciency. Thus, the problem of vulvar melanoma is a complex task that needs to be studied further.
Keywords. Vulvar melanoma, surgical treatment, sentinel lymph node biopsy, lymph node dissection, immunotherapy, targeted therapy
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Objective of the study is to carry out a systematic analysis of the data collected in current literature to evaluate the modifying effect of combined oral contraceptives on carcinogenesis of the cervix and uterus, liver and colon.
Materials and Methods. The review comprises the data of foreign and Russian academic articles found in PubMed on the subject, published over the past 10 years.
Results. Numerous international studies have confi rmed that taking combined oral contraceptives (COCs) reduces the risk of endometrial and colon cancer. And this protective effect lasts for more than two decades after the pills are discontinued. On the other hand, some studies report a risk of cervical cancer when using combined oral contraceptives (COCs). However, World Health Organization (WHO) experts claim that the benefi ts of using combined oral contraceptives (COCs) outweigh these risks. The risk of cervical cancer grows when combined oral contraceptives (COCs) are used for more than 5 years, and this elevated risk decreases after cessation of use to the point of being no higher than in those patients who never took combined oral contraceptives (COCs), within 10 years. Moreover, the overall risk can be further reduced by making lifestyle changes and human papilloma virus (HPV) vaccination.
Conclusion. Further research is needed in this regard.
Keywords: combined contraceptives, endometrial cancer, cervical cancer, liver cancer and colon cancer
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