Background. Core biopsy of the breast is currently considered to be the standard method of obtaining material for morphological and molecular genetic methods. Unfortunately, this method is associated with a number of problems, primarily the risk of complications (bleeding, pneumothorax) and discomfort during manipulation.
Aim. To analyze transcriptional signatures of breast tissue samples obtained by fine-needle aspiration biopsy. Materials and methods. Using reverse transcriptase polymerase chain reaction, we studied the mRNA expression level of 60 target genes in 60 samples obtained by fine-needle aspiration biopsy and in 60 corresponding formalin-fixed paraffin-embedded (FFPE) surgical specimens of breast. Samples were obtained from the tumor, adjacent tissue, the so-called tumor bed and formally normal tissue at a distance from the primary lesion.
Results. A comparative analysis of transcriptional signatures in samples obtained by fine-needle aspiration biopsy and FFPE specimens (120 samples in total) reveled the strongest correlations between transcriptional signatures in biopsy samples and FFPE specimens of tumors. Very strong correlation in tumor samples was established for one gene (CTSL2); strong for 18 genes (MKI67, MYBL2, NAT1, PTEN, TPX2, PTTG1, UBE2T, CCNB1, ESR1, CCND1, MYC, SCGB2A2, MIA, TRAC, FGFR4, ANLN, GSTM1, PRLR); averages for 28 genes (PGR, AURCA, KRT5, FOXA1, SFRP1, EMSY, EXO1, PAK1, KIF14, ERBB2, MMP11, BCL2, BAG1, TMEM45B, BIRC5, CD274/PDL1, ZNF703, TYMS, CCNE1, TPT1, TMEM45A, BRCA1, BRCA2, ESR2, STS, TNFSF11/RANKL, TNFRSF11B/OPG, TNF); weak for 4 genes (GRB7, EGFR, PGRMC1, CYP19A). The presence of correlations between transcriptional signatures in biopsy samples and FFPE specimens can be established in case of sufficient material corresponding to sample intake control (SIC) ≥5 lg for B2M gene.
Conclusion. The ability to conduct molecular genetic research on small samples of breast tissue makes it possible to obtain the material using the most minimally invasive method. And this, in turn, expands the possibilities of “genetic monitoring” of cancer, as well as the possibility of more accurate assessment the risks of malignant tumor development in the settings of benign conditions in women with fibrocystic disease and increased mammographic density.

Background. Atypical ductal hyperplasia is a relatively common breast lesion that increases the risk of breast cancer by 3.5 to 5 times. Genomic rearrangements underlying the development of atypical proliferative lesions and breast cancer lead to gene expression changings.
Aim. To determine the mRNA expression profile of neoplasia and oncogenesis driver genes in atypical ductal hyperplasia of the breast.
Materials and methods. The real-time reverse transcription polymerase chain reaction was used to explore the expression profile of 46 genes in 107 samples of formalin-fixed paraffin-embedded (FFPE) specimens from atypical ductal hyperplasia, ductal hyperplasia without atypia, ductal carcinoma in situ and normal breast tissue.
Results. In atypical ductal hyperplasia, we detected changes in the expression of 22 of 46 studied genes, including ESR1, AR, PRLR, FGFR4, MKI67, CCNB1, KIF14, PAK1, MMP11, GATA3, FOXA1, ZNF703, which were upregulated, and MYC, which was downregulated.
Conclusion. The transcriptional signature of atypical ductal hyperplasia was similar to that of ductal carcinoma in situ and breast cancer of luminal subtypes.

Background. Long-lasting dyshormonal breast diseases in women represent a risk factor for breast cancer, especially in patients with atypia. Clinical manifestations of fibrocystic breast disease (FBD) and mastopathy, including high-intensity pain cause psychoemotional discomfort and reduce the quality of life of women. The search for effective management strategies for mastopathy with an antiproliferative effect is highly relevant.
Aim. To assess clinical and radiological efficacy of a new conservative treatment for FBD, “Evening primrose oil” administered orally for 6 months in women with symptomatic FBD.
Materials and methods. This randomized, blind, placebo-controlled trial included 144 patients with clinical FBD manifestations (pain and tension in the breast). Patients were randomly assigned to one of the two treatment groups. Women in group I received “Evening primrose oil”, whereas women in group II received placebo (ascorbic acid) for 6 months. We measured the dynamics of radiological findings (at mammography and ultrasound examination) in the breast before and after treatment, as well as pain intensity using the visual-analog scale.
Results. Patients in group I with all types of FBD (diffuse mastopathy, nodular, and mixed forms) demonstrated positive dynamics and BI-RADS category downgrading within 6 months. In the placebo group, the examination after 6 months demonstrated no significant changes in the breast and no BI-RADS category downgrading among women with diffuse mastopathy. Some patients with nodular and mixed FBD receiving placebo had negative dynamics after 6 months (as demonstrated by mammography and ultrasound examination; BI-RADS category upgraded from II to III, p<0.01). Patients receiving “Evening primrose oil” also showed positive dynamics in their clinical manifestations, including decreased breast pain (from 7.8 to 1.8 on the visual analog scale). By contrast, patients receiving placebo had no changes in their breast pain intensity after 6 months (from 7.3 to 7.1 on the visual analog scale), which resulted in poorer psychoemotional state in 55.6 % of women.
Conclusion. Our new treatment strategy for FBD patients with clinical and radiological manifestations in the breast demonstrated high efficiency and can be implemented into routine clinical practice.

Background. Simultaneous breast reconstruction after subcutaneous or skin-sparing mastectomy using silicone implants is associated with a high risk of postoperative complications. Therefore, the issue of additional shell cover for breast implants is highly relevant. Synthetic and biological implants are believed to be the most effective.
Aim. To assess the efficacy and safety of autologous dura mater grafts in reconstructive surgeries for breast cancer patients.
Materials and methods. This study included 164 patients who had undergone subcutaneous or skin-sparing mastectomy with simultaneous breast reconstruction using implants and additional shell cover with either autologous dura mater grafts (experimental group, n = 83) or synthetic mesh implants (control group, n = 81) between 2017 and 2022. The mean patients’ age was 41.4 ± 7.2 years (41.2 ± 7.1 years in the experimental group and 41.6 ± 7.2 years in the control group). The mean follow-up time was 38.0 ± 21.4 months (min: 12 months; max: 80 months).
Results. The 3-year relapse-free survival rate was 100 %. The 3-year progression-free survival was 97.4 % (95 % confidence interval 92.6–100.0 %). We observed no significant differences in the time to disease progression between the experimental and control group (p = 0.573). The assessment of aesthetic outcomes using a special surgical questionnaire showed excellent cosmetic and psycho-emotional results. Patients in both groups demonstrated comparable cosmetic results (p >0.05); however, psychoemotional satisfaction with surgery results was higher in the experimental group (p<0.05). Postoperative complications (primarily capsule contracture) were registered in 18 patients from the experimental group (21.7 %) and 31 patients from the control group (38.3 %) (p0.05). We also calculated the incidence rate ratio (IRR) and found that the difference was due to different follow-up time. Clinically significant capsule contracture was observed in 9 patients from the experimental group (10.8 %). The incidence of capsule contracture was higher among patients who had radiation therapy than in those who had no radiation therapy (15.8 % and 0.0 %, respectively; p<0.05).
Conclusion. Subcutaneous or skin-sparing mastectomy with simultaneous breast reconstruction using silicone implants and autologous dura mater grafts is a safe and effective surgical method for breast cancer patients. The analysis of the international Breast-Q questionnaire results and surgical questionnaire results demonstrated that all patients had a high quality of life after simultaneous breast reconstruction using an autologous dura mater graft.

Background. The number of plastic surgeries is constantly growing worldwide. Breast augmentation remains the most common surgical procedure in women, which demonstrated a 0.5 % increase over the past 4 years. As the number of women with breast implants increases, specialists and patients themselves face difficulties related to screening, diagnosis, and treatment of tumors, including breast cancer.
Aim. To analyze specific characteristics of breast examination in patients after breast augmentation who were examined and treated in the mammological clinic of Russian Research Center of Radiology, Ministry of Health of the Russian Federation.
Materials and methods. This study included 273 patients aged between 21 and 63 years (mean age 49.0 ± 7.6 years) after breast augmentation and after reconstructive surgery for breast cancer and symmetrizing surgery on the contralateral side. All women underwent clinical examination plus breast ultrasound (for patients under 40 years of age) or mammography followed by ultrasound (patients over 40 years of age). Patients who were found to have BI-RADS 3–4 tumors underwent ultrasound-guided or stereotactic breast biopsy. In case of suspicious intraductal formations according to breast nipple smears the patients were referred to breast ductography. Patients with suspected implant rupture or capsular contracture, as well as patients requiring the assessment of the disease stage underwent contrast-enhanced magnetic resonance imaging.
Results. After comprehensive examination, 12 patients (5.4 %) were diagnosed with breast cancer; 38 patients (13.9 %), with implant rupture; 3 patients (1 %), with intraductal formations.
Conclusion. Breast augmentation is not a contraindication to mammography in women aged over 40 years with glandular tissue. Additional examination methods include breast ultrasound, contrast-enhanced mammography, and breast magnetic resonance imaging. In case of no glandular tissue, contrast-enhanced breast magnetic resonance imaging and breast ultrasound are the methods of choice. It is important to develop new standards of screening and diagnosis of breast diseases in women after aesthetic surgery, since breast cancer incidence is likely to increase among women after breast augmentation over the next decades, considering the fact that breast cancer is the most common malignancy in women and its incidence is constantly growing.

Background. Data on the prognostic role of the PIK3CA mutation in hormone receptor-positive (HR+) HER2-negative (HER2–) breast cancer (BC) are contradictory; nevertheless, there are indications of its negative predictive and prognostic significance. This dictates the need for early genetic testing of BC to predict the clinical course, select a primary therapy option and individualize systemic treatment with disease progression. Investigation of regulation of the tumor cell cycle, as well as the relationship between genetic markers, infiltration of tumor-infiltrating lymphocytes (TILs) and subpopulations of immune cells is strategically important for the search for drug therapy targets.
Aim. To search for predictive and prognostic markers of the clinical course of PIK3CA-associated HR+ HER2– BC.
Materials and methods. The clinical, morphological and molecular features of the tumor of 101 BC patients with PIK3CA mutations (100 women and 1 man) were analyzed. Early and locally advanced HR+ HER2– BC is present in 81 % of cases, where neoadjuvant chemotherapy (NAPCT) was performed in 28 % of patients. Primary metastatic disease was detected in 17 % of cases. An immunohistochemical evaluation was performed on sections from paraffin blocks using monoclonal antibodies to estrogen receptors, progesterone receptors, HER2, Ki-67, CD8, CD4, CD68, CD163, Bcl-2, p53, cyclin D1. TILs were evaluated when stained with hematoxylin and eosin. TILs were evaluated in the stromal component of the tumor. The correlation of clinical and morphological parameters with the type of mutation and clinical outcomes of treatment of patients with early and locally advanced HR+ HER2– BC was evaluated. The statistical analysis was performed using the IBM SPSS Statistics v. 22 statistical package.
Results. In BC with the PIK3CA mutation, a low level of TILs infiltration was detected (1 point), which does not differ depending on the presence of mutations in exon 20 and exon 9 (p >0.05). However, the E545K mutation is characterized by a higher TILs level (2 points) (p = 0.05). CD4+ T-TILs and CD8+ T-TILs levels are statistically significantly higher with mutations in exon 20 compared to exon 9 of the PIK3CA gene (p = 0.017 and 0.013, respectively). At the same time, in comparison with other mutations, tumors with H1047R and E545K mutations (p = 0.05) were characterized by a higher level of CD4 and CD8 expression. Regardless of the mutated exon, a high level of CD68+ tumor-associated macrophages (Me = 80 %), was detected due to the CD163+ fraction of immunosuppressive M2-polarized tumor-associated macrophages (Me = 70 %). A feature of the regulation of the PIK3CA-mutated BC cell cycle is the high level of cyclin D1 expression, the absence of p53 expression and the positive expression of the antiapoptotic marker Bcl-2. The median disease-free survival in early and locally advanced HR+ HER2– BC with the PIK3CA mutation was 36 months (95 % confidence interval (CI) 24.720–47.280). The risk of progression was increased by NAPCT (hazard ratio 3.389; 95 % CI 1.530–7.504; p = 0.003). The risk of progression was reduced by age younger than 49 years (hazard ratio 0.54; 95 % CI 0.30–0.96, p = 0.0359) and the absence of expression of the antiapoptotic marker Bcl-2 (hazard ratio 0.36; 95 % CI 0.14–0.97; p = 0.0425).
Conclusion. The data obtained indicate that BC with the PIK3CA mutation is a kind of biological subtype of HR+ HER2– BC, which shows the lack of significant efficacy of NAPCT, probably due to the immunosuppressive microenvironment and low TILs levels. At the same time, the predominant population was M2-polarized tumor-associated macrophages. Moreover, the administration of NAPCT and the positive expression of Bcl-2 reduce disease-free survival, which can be explained by the possible effect of increasing the invasiveness and migration potential of the tumor cell. It is important to continue investigation of identified clinical and morphological prognostic markers when planning and developing new strategies for the treatment of early and metastatic HR+ HER2– BC with the PIK3CA mutation, as well as the use of specific targeted therapy at early metastatic disease.

Breast cancer continues to maintain a leading position in the structure of the incidence of all oncological diseases among women. Early diagnosis of the disease at the stage of assessing indirect signs makes it possible in the future to maintain a good quality of life for patients by forming proper dynamic monitoring and performing functionally sparing surgical treatment. Interest in the early detection of benign and malignant pathology of the mammary gland is growing every year. A multidisciplinary approach to the study of the formation of breast calcifications makes it possible to look at the problem in a multifaceted way, and ways to solve problems in the process of diagnosis underlie the biochemical understanding of the mechanisms of formation, which is no less important when evaluating mammographic images. Practically up to 50 % of non-palpable breast tumors in practice are detected by signs of existing calcifications in the gland tissue. At present, the problem of early detection of malignant tumors of the breast by radiographic signs of these calcifications, their shape and nature of location in the gland tissue and their further pathomorphological confirmation is being actively studied.
We have analyzed the literature data of foreign and domestic authors over the past 20 years. The problem was considered from the mechanism of formation and morphological features of calcifications in the breast tissue to their radiographic assessment on mammographic images. According to the results of the studied literature, the biochemical features of the formations were taken as the basis for understanding the nature of calcifications in the breast tissue. On a biochemical level, calcifications are usually classified into two main types: type I, consisting of calcium oxalate, and type II, consisting of hydroxyapatite. The classification is based on chemical composition and mammographic characteristics, including morphology, distribution and density. Speaking about calcium oxalate, the benign nature of education is most often implied, which cannot be said about hydroxyapatite. Mammography is the main method for diagnosing these formations, taking into account the characteristics of the characteristic radiological signs, which are also detailed in this article.
Understanding the molecular and structural development of calcifications may aid in the detection and treatment of breast lesions. Identification of these structures in a patient diagnosed with breast cancer refers to the early diagnosis of the disease, where, with timely prescribed therapy, we get high chances of good long-term results of relapse-free survival.

Background. Cervical cancer is considered one of the most common and socially significant cancers of the female reproductive system. Despite the visual localization of the tumor, every second case is diagnosed at stage III–IV of the disease, when little can be done to help the patient, whereas early detection of the disease could help save the life and working capacity of young women.
Aim. To analyze the incidence of cervical cancer in Novokuznetsk for the period 2011–2020 by age groups and identify areas of risk for the development of the disease in order to develop effective and timely measures for early diagnosis.
Materials and methods. A database was formed on the basis of statistical reports of the Regional Clinical Oncological Dispensary (Novokuznetsk branch) for 2011–2020 with a unit of observation of 1 year, for some indicators, information is provided since 2008. The database analysis was carried out in the licensed statistical package IBM SPSS Statistics 19 using the following methods: Kendall’s tau correlation method (Ʈ), calculation of median values of indicators, upper and lower quartiles, Mann–Whitney test (U).
Results. In residents of Novokuznetsk for the period 2011–2020 a statistically significant increase in both absolute and relative (per 100,000 population) cervical cancer incidence was revealed. The risk zone for cervical cancer is 40– 44 years old.
Conclusion. When conducting preventive examinations and medical examinations of women, one should focus on the identified risk zone for cervical cancer. Conducting adequate and timely medical examinations seems to be a resource measure that contributes to the preservation of the life and health of women.

Aim. To identify the features of the systemic effect on hematopoiesis and the blood coagulation system of different histological subtypes of cervical cancer (CC).
Materials and methods. A single-center retrospective cohort study of 428 patients (61 patients with high grade squamous intraepithelial lesion (carcinoma in situ) and 367 patients with CC) examined from 1997 to 2022 in the Polyclinic of P. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiology Center, Ministry of Health of Russia. The age of patients was from 18 to 90 years (median age – 42 [34; 51] years). Patients were divided into 4 groups: group 1 – patients with high grade squamous intraepithelial lesion and 3 groups depending on tumor’s histological subtype (squamous cell, glandular squamous cell, adenocarcinoma). Demographic and clinical data were analyzed including laboratory tests (general blood count, biochemical blood test and iron metabolism and coagulograms (total 32 variables)) compared to clinical and surgical stages of CC.
Results. High grade squamous intraepithelial lesion does not have a systemic effect on the parameters of general, biochemical blood tests and hemostasis (p >0.05). On the other hand, statistically significant changes were found in the parameters of routine laboratory blood tests, which correlate with the results of microinvasive analysis of CC, thus revealing the systemic effect of a malignant tumor: at p ≤0.001 for thrombin time, total protein, alkaline phosphatase levels; at p ≤0.05 for alanine aminotransferase, aspartate aminotransferase, C-reactive protein, serum iron and urea levels. Among patients with CC, statistically significant (p<0.001) correlations were obtained between hematological, hemostasiological and biochemical blood parameters. Of statistical significance, the presence of the glandular component in the tumor increases the systemic effect of CC on blood parameters, hemostasis, markers of inflammation and iron metabolism: leukocytosis and maximum erythrocyte sedimentation rate values compared to CC, high fibrinogen and the level of soluble fibrin-monomer complexes which increased activation of coagulation hemostasis along the common coagulation pathway (thrombin time) (p<0.001). It leads to an increase in the risk of venous thromboembolic complications in this category of patients.
Conclusion. The identified changes in blood parameters made it possible to reveal the unique biological characteristics of each histological subtype of CC, including biochemical ones, which will help in developing an improved diagnosis of CC depending on the histological subtype and stage of the disease, along with developing preventive measures and treatment methods adapted to each specific case.

Aim. To assess the efficacy and safety of lenvatinib and pembrolizumab for the treatment of mismatch repair-proficient endometrial cancer (EC) in routine clinical practice in Russia.
Materials and methods. This multicenter, retrospective, cohort study included patients with recurrent and metastatic EC from 37 cancer centers in Russia treated between May 2020 and April 2023. Patients with histologically verified EC without microsatellite instability who received ≥1 course of pembrolizumab/lenvatinib therapy were included in the study. The primary endpoint was progression-free survival; the clinical characteristics of the patients were additionally analyzed, the objective response rate and the toxicity profile of therapy were assessed.
Results. The study included 100 patients. Median age was 65 (30–83) years. The most common histologic tumor subtype was endometrioid adenocarcinoma (68 %); serous adenocarcinoma was diagnosed in 22 % of cases, other types of tumor – 10 % of cases. All patients had pMMR/microsatellite-stable tumors. The median progression-free survival was 7.75 months (95 % confidence interval 0.7–33.8), and a partial response to therapy was observed in 24 % of patients. Almost half of the patients (44 %) required dose reduction due to adverse events. The most common adverse events included fatigue (n = 26; 26 %), hypertension (n = 20; 20 %), and hypothyroidism (n = 14; 14 %).
Conclusion. This study confirms the clinical efficacy of lenvatinib and pembrolizumab in patients with recurrent and metastatic EC without mismatch repair system deficiency (pMMR-tumors) in routine clinical practice.

The aim of this work is to analyze the main provisions of consensus, leading international organizations to identify significant ultrasound signs of ovarian tumors at the stage of preoperative diagnosis. Considering the fact that malignant ovarian tumors do not always have specific signs and are accessible to imaging methods, therefore, the risk stratification model in the system of reports and data on ovaries and appendages (O-RADS) is a useful tool that helps classify the formation of appendages into higher risk categories.

Each year, more than 400,000 children and adolescents under the age of 18 are diagnosed with cancer. The most common nosologies in childhood are leukemia, lymphoma and brain tumors. The use of chemoradiotherapy as an antitumor treatment in these cases is associated with a high risk of gonadotoxicity. The preservation of fertility in children and adolescents during malignant tumor therapy is one of the key aspects of treatment. To date, there are many unresolved issues in this problem, affecting the preservation of both physical and psychological health of patients in adulthood. The main methods of maintaining the reproductive function in girls are cryopreservation of ovarian tissue or oocytes, ovarian autotransplantation, the use of assisted reproductive technologies, including the techniques of in vitro fertilization and in vitro oocyte maturation, oophoropexy and neoadjuvant cytoprotective pharmacotherapy. The choice of fertility preservation method depends on many factors: the overall condition of the child, the type of malignant disease, the age and sexual status of the patient, the capabilities of the medical center, as well as legal and financial aspects. Due to the lack of information on pediatric oncofertility, large-scale multicenter clinical trials involving children and adolescents are needed.

Despite the existing standard treatments for endometrial cancer, the prognosis for these patients remained poor until recently. None of currently available cytostatics ensured long-term disease control and long-term survival of patients receiving standard platinum-based therapy. Poor treatment outcomes in patients with advanced endometrial cancer necessitated changes in therapeutic approaches and development of more effective treatment regimens. Better understanding of carcinogenesis mechanisms, emergence of a new molecular classification of endometrial cancer, and implementation of tailored treatment approaches based on tumor types led to a significant breakthrough in the treatment of advanced endometrial cancer. Currently, the most effective second-line therapy for endometrial cancer with high level microsatellite instability (MSI-h) or deficient mismatch repair system (dMMR) (25 % of cases), and no indications for surgery is pembrolizumab monotherapy. Most of cancers (about 75 %) are represented by microsatellite-stable and mismatch repair proficient tumors (MSS/рMMR). Patients with such tumors demonstrating disease progression after systemic therapy should receive a combinations of the immune checkpoint inhibitor pembrolizumab and the multi-targeted tyrosine kinase inhibitor lenvatinib. In this article, we review relevant literature and report a case of successful treatment of MSS/pMMR advanced endometrial cancer with a combination of pembrolizumab and lenvatinib as a second-line therapy (after disease progression in response to platinum-containing first-line chemotherapy), which ensured long-term disease control.