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Tumors of female reproductive system

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Vol 21, No 2 (2025)
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MAMMOLOGY. ORIGINAL REPORTS

16-25 10
Abstract

Background. Malignant neoplasms occur in 0.05–0.1 % of all pregnancies, breast cancer (BC) is the most common malignant neoplasm associated with pregnancy. The prognosis of this pathology remains a subject of debate due to conflicting research findings and requires a multidisciplinary approach to minimize risks for both mother and fetus. The prognosis of this pathology remains a subject of debate due to conflicting research findings and requires a multidisciplinary approach to minimize risks for both mother and fetus.

Aim. Identification of problems in clinical and morphological diagnostics of pregnancy-associated BC to improve treatment outcomes.

Materials and methods. This study included 35 patients over the age of 18 years with a diagnosis of breast cancer during pregnancy, who received treatment at the N.N. Petrov National Medical Research Oncology Center and the V.A. Almazov National Medical Research Center from May 2017 to March 2024.

Results. The average age of patients was 35.34 ± 3.57 years. The diagnosis was established on average at 23 weeks of pregnancy, at stages II–III of the disease. 21 patients (60 %) were estrogen-receptor- and progesterone-receptornegative by the immunohistochemical subtype. Genetic mutations were detected in 30.3 % of cases. Pregnancy was terminated in 3 (8.8 %) patients. Systemic therapy during pregnancy was performed in 18 (51.4 %) patients, surgery – in 3 (8.6 %) patients, and 11 (31.4 %) women refused treatment during pregnancy and started it only after delivery. Progression of BC was detected in 8 (22.9 %) of cases. Locoregional recurrence was diagnosed in 1 (2.9 %) patient.

Conclusion. The complexity of treatment and the growth of the population of patients diagnosed with pregnancyassociated BC confirm the need for analysis of individual cases, multicenter studies, and the creation of a common registry to determine clear algorithms for diagnosis and management of this pathology. For timely diagnosis of BC during pregnancy, it is necessary to conduct examinations of the mammary glands (ultrasound diagnostics) in early stages of women over 30 years of age. It is necessary to further study the division of the concepts of diagnosis of BC during pregnancy and BC during lactation (for at least 3 years after delivery) for a more accurate assessment of the prognosis of the disease and optimization of recommendations for the management of these patients.

26-33 7
Abstract

Aim. To evaluate the efficacy of interstitial high-dose rate brachytherapy (HDRB) or irradiation by electron as the methods for delivering boost to the tumor bed.

Materials and methods. We performed a retrospective analysis of 5-year local control after whole breast irradiation and additional boost delivery to the tumor bed by HDRB or by electrons. In 485 breast cancer patients included in the analysis HDRB boost was performed in 247, by electrons – in another 238 women.

Results. In 485 evaluated patients, local recurrences were diagnosed in 22 (4.5 %) cases: in 10 (4.0 %) of 247 women after HDRB boost and in 12 (5.0 %) of 238 patients who received a boost by electrons (р = 0.536). We found that age less than 50 years and aggressive subtypes (triple-negative, HER2+, luminal B HER2+) were associated with an increased risk of local recurrence (р = 0.003 and р = 0.004, respectively). The type of boost delivery (HDRB vs. electrons) does not influence the probability of local control in young women (р = 0.547) or in patients with aggressive subtypes of breast cancer. Conclusion. Both techniques of boost delivery (HDRB or electrons) are equally effective in prevention of local recurrence.

34-46 6
Abstract

Aim. To investigate the possibility of using radiation diagnostic data to determine various molecular subtypes of breast cancer (BC) using artificial intelligence technologies.

Materials and methods. The material for the study was retrospective data of 344 patients treated at the Sverdlovsk Regional Oncology Dispensary in the period from 2021 to 2023. The average age of the study sample was 56.8 ± 10.6 years, ranging from 33 to 82 years. All patients were diagnosed with BC, confirmed histologically. Molecular subtypes of BC were assessed based on trepan biopsy and surgical material. All patients underwent mammographic, ultrasound, and magnetic resonance imaging examinations, and sets of diagnostic features were identified that most accurately correspond to various molecular subtypes of BC. To achieve this goal, the authors identified the following diagnostic features: age, maximum diameter of the formation measured for various methods of radiation diagnostics, morphological features (contours, spatial orientation, shape of the detected formations or areas of reconstruction, heterogeneity of the structure of formations, presence of calcifications, characteristics of blood flow in the tumor) and dynamic parameters of paramagnetic accumulation during magnetic resonance imaging of the mammary gland.

Based on the histological examination data, the degree of tumor differentiation (G), proliferative activity index (Ki-67), regional lymph node status (presence or absence of metastases), and molecular-immunohistochemical tumor subtype were assessed. An analysis was conducted to determine whether there was a statistically significant relationship between diagnostic features and molecular subtypes of BC. The analysis was performed by conducting chi-square tests for features and subtypes (classes) of BC, previously converted to binary form. From the arrays of values s  elected for the study of diagnostic features, training and test samples were formed, and an algorithm for the classification model of artificial intelligence was determined. The accuracy of BC typing was ensured by using a combination of 7 diagnostic features and 6 classification models: five single-class and one multi-class. The gradient boosting algorithm (GradientBoostingRegressor) was used to train single-class models. The strategy “one (class) versus the rest” was used to train the multi-class model using the OneVsRestClassifier and gradient boosting (GradientBoostingClassifier) algorithms. The quality of the trained model was tested on test data. Statistical data processing, development of classification models, their testing and assessment of the quality of training were performed in the Jupyter Notebook environment v.6.5.2.

Results. The training quality indicators of single-class models for recognizing BC subtypes were as follows: sensitivity in determining luminal A subtype (LA) was 67.0 %, luminal B subtype (LB) – 72.7 %, luminal B HER2-positive subtype (LBH) – 81.8 %, non-luminal HER2-positive (HER) and triple negative breast cancer (TNC) – 100 %. The specificity was 90.2 % for LA, 83.0 % for LB, 89.7 % for LBH, 98.3 % and 93.5 % in the cases of HER and TNC, respectively.

The area under the ROC curve (AUC) depending on the molecular subtype was determined as follows: for LA – 0.88, for LB – 0.86, for LBH – 0.87, for HER – 0.96, and for TNC – 1.000. The multiclass model also showed low sensitivity values, except for the TNC (100 %) and HER (85.7 %) subtypes, low levels of positive predictive value for all subtypes, except for TNC (91.7 %), and high specificity and negative predictive value for all subtypes. The area under the ROC curve for the multiclass model was for the subtypes: LA – 0.88, LB – 0.86, LBH – 0.86, HER – 0.95 and for TNC – 1.00.

Conclusion. The possibility of using certain combinations of diagnostic features obtained as a result of radiation diagnostic methods to determine the probability of a molecular biological subtype of BC was proven. This indicates the presence of prerequisites for the creation of a new diagnostic tool for typing BC using classification models of artificial intelligence. In the future, its implementation will reduce the likelihood of an error in determining the molecular biological subtype of BC, especially in situations where the doctor»s opinion and the results of the immunohistochemical study do not coincide.

MAMMOLOGY. REVIEWS

47-59 5
Abstract

This review presents the relevance of escalating pathogenetic treatment in patients with hormone receptor-positive breast cancer, identifies key goals for prescribing adjuvant combined endocrine therapy with CDK4 / 6 inhibitors in patients with stage II–III breast cancer, and presents 3- and 4-year results of the randomized controlled trial NATALEE. Studies comparing oncological outcomes of “traditional” drug regimens and combined endocrine therapy with ribociclib in patients with similar characteristics are demonstrated. Data on estimating the size of a population of patients with characteristics equivalent to those in the NATALEE trial for prescribing ribociclib in routine practice are presented.

60-68 1
Abstract

Breast cancer (BC) is one of the most common forms of malignant neoplasms among women and is the leading cause of cancer-related mortality. This complex and heterogeneous disease is formed depending on the presence of overexpression of various receptors on the surface of tumor cells. Despite significant advances in the therapy of early and metastatic BC, many patients continue to demonstrate disease progression against the background of traditional treatment methods, which indicates immunosuppression or a defect in the immune system.
The aim of this work is to review the scientific literature on the main mechanisms of antitumor immunity in patients with BC and the prospects for the use of immunotherapy.
Previously, BC was not considered a particularly immunogenic tumor, but new data show that different tumor subtypes can exhibit immunogenicity, which opens up new prospects for the use of immune checkpoint inhibitors. Features of the tumor immune microenvironment and the presence of tumor infiltrating lymphocytes are becoming important markers that help predict responses to immunotherapy. The effectiveness of such approaches is demonstrated by clinical studies, where the use of immune checkpoint inhibitors in combination with chemotherapy has shown an improvement in the response to therapy. Such studies confirm that even in cases where there is a residual tumor after neoadjuvant treatment, the use of immunotherapy can increase survival. From the presented analysis of literature sources, it follows that BC carcinogenesis is accompanied by suppression of the antitumor activity of the immune system. Quantitative analysis of various predictors allows us to determine the effectiveness of immune drugs. Thus, given the diversity of BC subtypes and many factors affecting the effectiveness of treatment, it becomes obvious that careful patient selection and a personalized approach to immunotherapy are necessary to achieve optimal results. In the future, research in the field of biomarkers should be continued to better predict the response to immunotherapy and minimize adverse effects.

69-74 4
Abstract

The surgical stage is the main one in the complex and combined treatment of patients with breast cancer. After performing skin-sparing and subcutaneous mastectomies, there is a risk of postoperative complications in the form of skin flap necrosis associated with its insufficient perfusion. In order to reduce the incidence of postoperative complications, it is necessary to improve the quality of intraoperative assessment of skin flap perfusion after reconstructive plastic surgery on the mammary gland. This article reviews the literature on current issues of assessing the efficacy and safety of this technique. Indocyanine green angiography has been proposed to assess skin flap perfusion. 
The method involves intraoperative injection of dye followed by illumination of the skin flap to assess perfusion and remove non-viable tissue.

75-83 3
Abstract

The presented work is devoted to modern concepts of basic therapy of dyshormonal dysplasia – the most common diffuse disease of the mammary glands. In Russia, one of the most popular medications for the specific correction of mastalgia–mastodynia associated with this disease is Mastodinon. The active component of the drug – the extract of Vitex agnus-castus (chaste tree, monk’s pepper) contains the flavonoid casticin, which determines the therapeutic potential of this plant. The authors present the latest data from the world literature on the clinical and biological effects of сasticin as well as its molecular effects on the processes of epigenetic rearrangements in benign breast dysplasia. Also the potential role of casticin in the prevention of cancer was assessed.

GYNECOLOGY. ORIGINAL REPORTS

84-90 4
Abstract

Background. The field of medicine that studies the possibility of preserving reproductive function in cancer patients is intensively developing in the world. Many countries are studying this issue by creating their own databases and national guidelines. In Russia, despite the interest in this problem and discussions at many national conferences, there are no national programs, protocols and clinical recommendations. It creates an obstacle to receiving this type of care for cancer patients. In this regard, the creation of an interdisciplinary system on the preservation of reproductive function in cancer patients becomes relevant. Aim. Formation of interdisciplinary relations between oncologists / hematologists, obstetricians-gynecologists and fertility doctors in order to improve the effectiveness of the care provided on fertility preservation in cancer patients.

Materials and methods. The study involved oncologists from the S. S. Yudin City Clinical Hospital, Moscow Healthcare Department, obstetricians-gynecologists and hematologists from the City Clinical Hospital No. 52, Moscow Healthcare Department, as well as reproductive health specialists from the Institute of Reproductive Medicine REMEDI. Oncological patients were recruited on the basis of the S. S. Yudin City Clinical Hospital. A standard scope of examination was undertaken and they were offered antitumor treatment within the framework of the tumor board, taking into account the stage of the disease and the morphological type of the tumor. An obstetrician-gynecologist received patients on the basis of the City Clinical Hospital No. 52. An individual card specially designed for this study was filled in for each patient. The card included data on anamnesis, examination and additional examination methods. A reproductive health specialist received patients on the basis of the Institute of Reproductive Medicine REMEDI. The information obtained during the consultations was added into the specially designed cancer fertility register, with a subsequent assessment of each patient’s status. Results. A multidisciplinary team on fertility preservation was formed with a clear routing of cancer patients when referring to appropriate specialists. Since 2023, 42 oncological and hematological patients have been consulted. A unified database on oncofertility was set up.

Conclusion. Our study confirms the need to create a multidisciplinary team to address the issues of preserving reproductive function in cancer patients, providing adequate information to patients about the risks of developing premature ovarian failure during treatment, about possible options for preserving fertility, improving the quality of life and the likelihood of childbirth after the completion of antitumor treatment.

91-99 3
Abstract

Background. Cervical intraepithelial lesion with human papillomavirus (HPV) is one of the most common HPV-associated diseases. In recent years, immunocytochemical detection of p16 / Ki-67 coexpression has been considered as an additional method for confirming precancerous and cancerous cervical lesions, with high sensitivity and specificity.

Aim. To determine the detection rate of p16 / Ki-67 coexpression depending on the degree of intraepithelial lesion, human papillomavirus genotype, viral load, and the presence of coinfection. To calculate the performance indicators of the immunocytochemical method and the polymerase chain reaction method for detecting HPV DNA for the diagnosis of severe intraepithelial lesions and cervical carcinoma (cervical intraepithelial neoplasia, CIN 2+).

Materials and methods. The study included material from 129 patients. Depending on the degree of cervical lesion, the following groups were formed: low-grade squamous intraepithelial lesion (CIN 1), high-grade squamous intraepithelial lesion (2–3), carcinoma. The comparison groups included patients without intraepithelial changes and with negative / positive results for HPV DNA. Coexpression of p16 / Ki-67 was assessed using immunocytochemistry, HPV DNA was determined by real-time polymerase chain reaction. The results were evaluated in comparison with histology. Results. The frequency of detection of positive p16 / Ki-67 immunocytochemistry depending on the degree of dysplasia and carcinoma of the cervix: CIN 1 – 26.5 % (n = 9), CIN 2 – 59.3 % (n = 16), CIN 3 – 88.2 % (n = 15), squamous cell carcinoma – 88.9 % (n = 8). Co-expression was more often detected in the presence of HPV infection of genotypes 16, 18 and 31. The median viral load was higher in the presence of double staining p16 / Ki-67 and amounted to 6.21 lg, in the absence of coexpression – 5.02 lg. No statistically significant differences were found in the frequency of detection of co-expression of p16 / Ki-67 depending on the number of HPV genotypes in the material. The efficiency indicators of the method for diagnosing CIN 2+ were: sensitivity 73.58 %, specificity 82.35 %.

Conclusion. A positive coexpression of p16 / Ki-67 is more often detected in severe intraepithelial lesions of the cervix and the presence of HPV genotypes 16, 18 and 31. Immunocytochemical method of assessing p16 / Ki-67 coexpression is more specific in the diagnosis of precancerous and cancerous diseases of the cervix compared to the detection of HPV DNA.

100-107 5
Abstract

Aim. To evaluate the risk factors associated with pregnancy loss in the studied cohort; to establish the clinical relevance of leukocyte-derived proteolytic enzymes as biomarkers of pregnancy loss; to develop a diagnostic and prognostic approach for early detection of pregnancy loss.

Materials and methods. The study included 152 participants aged 18 to 40 years: 35 conditionally healthy pregnant women and 117 patients diagnosed with threatened miscarriage at 5–6 weeks of gestation. These patients, based on the activity levels and quantity of leukocyte-derived proteolytic enzymes and/or pregnancy outcomes, were divided into three groups: 35 patients with a missed miscarriage, 35 patients with a complete spontaneous abortion, and 35 patients with an incomplete spontaneous abortion. The diagnosis of threatened miscarriage was established based on clinical presentation (complaints of lower abdominal cramping and/or vaginal bleeding), as well as ultrasound findings (presence of a gestational sac in the uterine cavity). The diagnosis of complete spontaneous abortion in the main group was based on the absence of a gestational sac in the uterine cavity as confirmed by ultrasound and/or the identification of chorionic tissue on histological examination. The diagnosis of incomplete spontaneous abortion was based on the presence of retained products of conception in the uterine cavity and confirmation of chorionic tissue in histological analysis. The diagnosis of a missed miscarriage was based on deformation of the gestational sac and/or absence of embryonic cardiac activity on ultrasound. To assess cathepsin activity, biochemical assay kits were used, and the resulting data were analyzed using spectrofluorimetric methods.

Results. The new method for early diagnosis of pregnancy loss possesses high sensitivity and specificity. Conclusion. The study confirmed that cathepsins are markers of miscarriage, and a method for early diagnosis and prediction of this pregnancy pathology before its clinical manifestations and pregnancy outcome was developed.

108-114 2
Abstract

Aim. To describe the immediate and long-term results of a series of cases of the use of epoetin alfa in preoperative therapy of malignant tumors of the female reproductive system, performed at a single clinical center.

Materials and methods. The article presents the experience of treating anemia (2–3 degrees of severity) of various origins with erythropoiesis-stimulating drugs in monotherapy or in combination with iron preparations in 5 patients who sought medical care at the Federal Research and Clinical Center for Specialized Medical Care and Medical Technologies, Federal Biomedical Agency of the Russian Federation for the period from August 2024 to February 2025 due to malignant tumors of the female reproductive system of various localizations, for whom surgical treatment was indicated.

Results. The mean age of patients at the time of surgery was 55.4 ± 32.5 years. The mean body mass index of patients was 25.6 ± 1.6. The mean hemoglobin level in the blood at the time of diagnosis was 78.2 ± 3 g / L. The mean duration of preoperative drug therapy was 4.4 ± 1.5 weeks, during which 2 (40 %) patients received monotherapy with epoetin alfa (40,000 IU once a week subcutaneously), 3 (60 %) patients with serum ferritin <100 ng / ml and serum transferrin iron saturation <20 % – combination therapy in combination with iron [III] hydroxide sucrose complex (intravenous jet stream 200 mg 3 times a week). The mean hemoglobin level at the time of surgery was 102.2 ± 8.5 g / L. The average postoperative hospital stay was 7.2 ± 5.5 days. No intra- or perioperative complications were observed. The average postoperative follow-up period was 7 (3–9) months, during which no recurrence of the disease was detected (0 %).

Conclusion. The correction of multifactorial anemia of 2–3 degrees of severity in the preoperative period in malignant tumors of the female reproductive system using erythropoietins in monotherapy or in combination with iron preparations within a reasonable time ensures the achievement of the target hemoglobin level for subsequent surgical treatment, an acceptable quality of life for patients, and also allows to reduce the risk of perioperative complications and avoid unnecessary blood transfusions.

GYNECOLOGY. REVIEWS

115-122 8
Abstract

The review systematises literature data on pathogenesis, clinical course and treatment of benign metastasising leiomyoma. Benign metastatic leiomyoma is a rare disease, occurring in women of reproductive period, characterised by the presence of multiple benign indolent smooth-muscle mitotically inactive tumours (metastases) of ectopic localisation with a history of uterine leiomyoma and no other tumour process. It is presented in various forms: peritoneal leiomyomatosis, intravenous leiomyomatosis involvement of parenchymal organs, bones, skeletal muscles. Currently, there are no standards for the treatment of patients with benign metastasising leiomyoma. Treatment depends on localisation of metastases and clinical manifestations of the disease: dynamic observation, hormone therapy or surgical treatment.

123-126 7
Abstract

Oleogranuloma of the breast is a benign neoplasm that imitates breast cancer, which necessitates differential diagnostics between these pathologies. In this article, we have examined in detail the manifestations, diagnostic methods, and treatment of oleogrаnuloma of the mammary gland.

127-134 7
Abstract

Endometrial cancer (EC) remains the most common gynecologic oncology disease in Russia, with a tendency toward increasing incidence and associated mortality. In recent years, significant progress has been made in understanding the molecular mechanisms underlying the disease, leading to the development of a molecular classification of EC, which has enabled the implementation of personalized treatment approaches. Determining the status of microsatellite instability (MSI) and deficiency in the mismatch repair system (MMR), as well as identifying mutations in the POLE and TP53 genes, has become a key component in diagnosis and decision-making regarding therapy. The combination of lenvatinib and pembrolizumab has demonstrated clinical efficacy in pMMR / MSS EC in the second-line setting. The Study 309 and LEAP-001 trials confirm the clinical benefit of lenvatinib and pembrolizumab in patients with pMMR / MSS tumor phenotypes following prior adjuvant therapy. Expert consensus highlights the necessity of testing all patients for dMMR / MSI at initial EC diagnostics and supports the use of immunotargeted therapy with lenvatinib and pembrolizumab already in the first-line setting for patients with pMMR / MSS phenotype and prior adjuvant systemic therapy.

The aim of this review is to analyze current approaches to systemic therapy for EC, assess the clinical significance of lenvatinib and pembrolizumab therapy, and examine the role of molecular diagnostics in guiding treatment decisions.

GYNECOLOGY. CLINICAL CASE

135-144 10
Abstract

Borderline ovarian tumors (BOT) are neoplasms with low malignant potential, which are characterized by atypical epithelial proliferation without destructive stromal invasion. They account for 15–20 % of all epithelial ovarian tumors, with serous and mucinous BOT being the most common. The incidence of BOT ranges from 1.5 to 4.8 cases per 100,000 women, with at least one-third of patients being younger than 40 years at the time of diagnosis. Therefore, one of the most critical aspects of treatment is fertility preservation. The “gold standard” for organ-sparing treatment is resection of the affected ovary or adnexectomy, accompanied by mandatory surgical staging. Most BOT are diagnosed at early stages (FIGO I), ensuring a favorable prognosis with a 5-year survival rate of 95 % and a 10-year survival rate of 90 %. Recurrences occur in 5–34 % of cases, most often as borderline tumors and less frequently as invasive ones. Although conservative treatment is considered one of the risk factors for subsequent recurrences, its impact on overall survival has not been proven. We describe a clinical case of fertility-sparing treatment for a recurrent during second pregnancy BOT, initially diagnosed in a young woman during the first trimester of her first pregnancy.



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ISSN 1994-4098 (Print)
ISSN 1999-8627 (Online)