MAMMOLOGY. REVIEWS
Carriers of germline mutations have an increased risk of developing malignant neoplasms. Mutations in the BRCA1/2 gene are the most studied, leading to an increased risk of breast cancer, characterized by early manifestation and aggressive course. The development of screening measures aimed at identifying tumors characteristic of certain mutations will increase the patient’s chances for radical treatment, and therefore lower costs for the treatment of advanced forms of malignant neoplasms. It is important to know the correlation of mutations with the characteristics of their clinical manifestation, the study of this issue will lead to the formation of a medical and economic justification for additional diagnostic procedures.
MAMMOLOGY. ORIGINAL REPORTS
Background. The analysis of the incidence of benign breast disease (BBD) allows you to control the prevalence of the disease in the population and plan medical care.
Aim. To study the incidence and prevalence of BBD on the example of the Sverdlovsk region in 2012–2021 and Yekaterinburg in 2012–2020.
Materials and methods. An observational epidemiological retrospective study of the incidence of BBD in women aged 18 years and more was conducted. To calculate the indicators, we used the form of Federal statistical observation No. 12 for Yekaterinburg and recommendations by the Federal State Statistics Service, Russian Research Institute of Health. We analyzed the indicators of the incidence of BBD in the Sverdlovsk region, published on the websites of the Ministry of Health of Russia and the Russian Research Institute of Health. Information on the number of women examined for oncopathology was obtained from Form No. 30 “Information about a medical organization” in 2016–2020.
Results. The incidence of BBD in the Sverdlovsk region increased in 2013–2019 and Yekaterinburg 2015–2019 compared to 2012 (p <0.001). During the pre-pandemic period, the average growth rate of the indicator was 5.20 % in the region, 7.60 % in the city. The incidence of BBD in the city annually exceeded the regional indicator in 2012–2019 (p <0.028). The prevalence of BBD followed the trends of the incidence (p <0.001). The average growth rate of the total incidence in the region was 7.55 %, in the city – 9.57 %. A decrease in incidence rates in the region and the city in 2020 compared to 2019 was incidence (p <0.001). A positive correlation was established between the number of cases of newly diagnosed ВВD and the number of women examined for oncopathology in the region (r = 0.924 at p = 0.025) and the city (r = 0.900 at p = 0.037).
Conclusion. The incidence and prevalence of BBD in the female population of the region and the city significantly increased in the pre-pandemic period. There was a decrease in indicators due to the massive and rapid spread of a new coronavirus infection and restrictive measures aimed at containing it in 2020–2021.
Background. Breast cancer (BC) has been ranked first in morbidity and mortality among the female population in Russian Federation for several years. Rapid and accurate intraoperative examination of the cleanliness of resection margins is the main condition for breast-conserving surgery (BCS) to reduce the risks of local recurrence.
Aim. To examine the tumor margins and assess the cleanliness of the resection margins in BCS in patients diagnosed with BC using multimodal optical coherence tomography (MM OCT) with comparative planned histological and additional molecular genetic analysis.
Materials and methods. The study was carried out on postoperative samples of tumor and non-tumor breast tissue obtained from 115 patients with BC T1–2N0M0G2–3 stage IA–IIA, after BCS in the volume of radical resection or lumpectomy with histological control of the resection margins. A spectral domain MM OCT device (OCT 1300-E, BioMedTech LLC, Russia) was used, which provides structural OCT images to study the backscattering properties of tissue and allows performing a quantitative assessment of the elastic properties of the tissue by compression optical coherence elastography (OCE).
Results. The MM OCT method was able to determine the exact margins between the tumor and non-tumor breast tissue. The main signs of the tumor were a decrease in the level and depth of penetration of the OCT signal in the structural OCT images, as well as an increase in the stiffness values (>200 kPa) in the OCE images with the highest stiffness values (>600 kPa) in the area of tumor cell accumulations. The use of compression OCE made it possible to detect clusters of tumor cells in the margins of resection at a distance of 5 mm from the visible border of the tumor. Among the 132 studied resection margins in 6 cases, the positive resection margin was determined by the OCE method, which was subsequently confirmed histologically. The negative resection margins were characterized by the lowest stiffness values (<200 kPa) in the OCE images and were confirmed by both histological analysis and molecular genetic analysis. ROC-analysis established a threshold stiffness value of 159.8 kPa, which indicates the presence of tumor tissue at the resection margins in the presence of a high stiffness area larger than 500 µm. The high diagnostic accuracy of the OCE method (98.5 %) was determined to distinguish between the negative and positive resection margins during BCS.
Conclusion. The use of MM OCT with OCE modality makes it possible to clearly distinguish different types of breast tissue in BC (adipose tissue, connective tissue, accumulation of tumor cells). MM OCT can be used as an additional intraoperative tool for visualizing tumor cells boundaries and assessing the cleanliness of resection margins in real time during BCS.
Background. Breast cancer (BC) is not only a global medical problem, but a social problem associated with its steady growth and spread. Thus, the prevalence of BC in women in Russia in 2021 was 21.1 %. Combined or complex treatment is used in the vast majority of cases (surgery, drug and radiation therapy); in 2021, this percentage was 64.5 %. Currently, there is no doubt that radiation therapy is necessary as part of the complex treatment of patients with T1–3N1–2 BC, as it leads to an increase in survival rates. The development of reconstructive plastic surgery makes it possible to restore the removed breast using implants or autologous tissues. Reconstruction with endoprostheses is the main method, it accounts for up to 70 % of all reconstructive breast surgeries. Until recently, the most popular method was a two-stage reconstruction. Especially in cases where radiation therapy is planned. However, our own experience of one-stage reconstructions in combination with radiation therapy showed good aesthetic results with a low complication rate, which was the reason for this study.
Aim. To study and compare the incidence of complications in one- and two-stage breast reconstruction after subcutaneous/skin-sparing mastectomy in combination with radiation therapy.
Materials and methods. A prospective study of 92 patients diagnosed with BC was carried out. The patients were divided into 2 groups: group I (study) included 50 women, who underwent one stage – subcutaneous/skin-sparing mastectomy with breast reconstruction using an implant, II (control) group included 42 patients, who underwent subcutaneous/skin-preserving mastectomy with breast reconstruction with an expander, followed by replacement of the expander with an implant. After radiation therapy, the groups underwent a comparative assessment of anthropometric and anamnestic data, a study of the somatic anamnesis, the results of pathomorphological typing of the tumor, treatment tactics and complications.
Results and conclusion. Subcutaneous/skin-sparing mastectomy with simultaneous breast reconstruction using an implant does not increase the incidence of postoperative complications when combined with radiation therapy, and also does not limit the appointment of concomitant treatment methods in the complex therapy of women with BC. This method of surgical treatment can be used in patients with IIA, IIB and IIIA stages of tumor growth.
Breast cancer is the most common cancer in women and one of the leading causes of death from cancer in Russia and most countries of the world. In countries with mammographic screening, there is a decrease in mortality from breast cancer. Introduction of mammographic image evaluation platforms into radiologist practice based on the work of artificial intelligence it allows not only to increase the coverage of the female population, but also to reduce the cost of screening, but it also increases the sensitivity and specificity of mammography as a method of breast cancer screening.
The article presents the results of a study on the evaluation of mammographic images in women who have passed a preventive study using an artificial intelligence program.
Within the framework of this project, mammographic images were analyzed using the service for viewing medical images “Celsus” in 8030 patients. The study assessed the age groups of 40-49 years, 50-59 years, 60 years and older. The average age of patients with suspected breast cancer was 54.8 years. Breast cancer was detected in 13 women (1.2 %), while the highest percentage of breast cancer was detected in the group with mammographic density D.
Background. Breast cancer is distinguished by its heterogeneity. The biological subtype of the tumor influences the choice of treatment tactics, components of complex therapy. The appearance of targeted drugs made it possible to expand the indications of reconstructive plastic surgery in patients with breast cancer.
Aim. To study the influence of the biological subtype of breast tumor on the frequency of complications after simultaneous and delayed reconstructive plastic surgeries.
Materials and methods. The postoperative period of 577 patients 18–40 years with a diagnosis of stage I–IIIA unilateral breast cancer was studied. In 61.2 %, luminal cancer, subtype A, was verified, in 6.1 % – luminal cancer, subtype B, in 10.4 % – HER2-positive (luminal) ER+PR+, in 7.3 % – HER2-positive (non-luminal) ER–PR–, in 15 % – three times negative. All patients underwent surgical treatment, including, taking into account the indications and contraindications, in the volume of Madden mastectomy – 43.5 %, mastectomy with simultaneous two-stage reconstruction with silicone implants – 34.8 %, mastectomy with delayed two-stage reconstruction with silicone implants – 21.7 %.
Results. In most patients, the early postoperative period was favorable, complications were recorded in 11.8 %: in 11.3 % of patients of group I, 11.4 % of group II, 11.7 % of group III, 14.3 % of group IV, 12.6 % of group V. After radical mastectomy, complications were recorded in 13.5 % of cases, after mastectomy with simultaneous and delayed reconstruction – in 10.4 %. The treatment efficacy rate was 65.2–84.6 %. Late postoperative complications were recorded in group I in 24.1 % of patients, in group II – in 22.9 %, in group III – in 23.3 %, in group IV – in 26.2 %, in group V – in 24.1 %. Among patients who underwent only radical mastectomy, complications were noted in 24.7 %, mastectomy with simultaneous reconstruction – in 24.9 %, mastectomy with delayed reconstruction – in 21.6 %. The treatment efficacy rate was 42.9–59.5 %.
Conclusion. Our study did not reveal a relationship between the incidence of early and late postoperative complications in patients with different biological tumor types. Based on the literature, it can be assumed that not the type of tumor, but individually prescribed systemic therapy makes a significant contribution to the development of postoperative complications, which should be taken into account when planning reconstructive plastic surgeries.
Neutropenia is a common complication during anti-cancer therapy. Risk factors for febrile neutropenia, its diagnostic criteria, and methods of its prevention and treatment have been well described. In this article, we demonstrated the need to assess cost effectiveness of primary prevention of complications associated with polychemotherapy and treatment of neutropenia, as well as the need to analyze their incidence. Individual risk assessment of febrile neutropenia, implementation of the antimicrobial drug registry, and administration of pegylated granulocyte colony-stimulating factor reduced the incidence of neutropenia, its duration, and the number of antimicrobial drugs used. This, in turn, improved the quality of healthcare and optimized the use of hospital resources.
Background. New biomarkers of breast cancer are actively being studied to used them for breast cancer prognosis and develop optimal approaches to therapy. FOXA1 is one of these factors whose prognostic value for breast cancer has been analyzed in several studies.
Aim. To evaluate the prognostic value of FOXA1 in patients with T1–2N0M0 breast cancer.
Materials and methods. We measured FOXA1 expression in tumor cells of patients with hormone-dependent and hormone-independent breast cancer using the method developed by us (patent No. RU2748716C1 dated 03.06.2020). We performed immunohistochemical examination of tumor tissue using specific antibodies for staining. The Allred scale was used for results interpretation (to assess the number of cells with stained nuclei and the intensity of their staining). Then the total Allred score was calculated and used as a prognostic parameter. Patients with the Allred score between 4 and 8 had a favorable prognosis. We followed up patients in the groups and evaluated their survival. A univariate analysis was used to assess the risk of lethal outcome depending on the level of FOXA1 expression.
Results. In 75 % of patients with hormone-dependent and 82 % of patients with hormone-independent breast cancer (stages T1–2, N0 in both groups), the prognostic parameter measured using the Allred scale ranged between 4 and 8 points; their 10-year overall survival was 93 % and 92 %, respectively.
Conclusion. Our findings suggest high accuracy of our method for breast cancer prognosis. It can be used for breast cancer prognosis in early stages (T1–2, N0) and expands the range of techniques for breast cancer prognosis.
Aim. To evaluate the prognostic value of CD4+ in patients with T1–2N0M0 breast cancer.
Materials and methods. We performed a quantitative assessment of CD4+ T-lymphocytes in tumor stromal cells and determined the prognostic parameter using the method developed by us (patent No. RU2697709C1 dated 19.08.2019) in 394 patients diagnosed with infiltrative breast cancer. Survival of patients in the analyzed group was assessed over a period of 10 years.
Archival material from paraffin blocks of the «target group» was used in the work for molecular genetic profiling techniques (T1–2N0M0, 1118 patients, 2000–2009). A histological preparation stained with hematoxylin and eosin was scanned, and the central and peripheral zones of the tumor were isolated. To identify CD4+ T-lymphocytes, the immunohistochemical study of preparations obtained with rabbit anti-CD4 monoclonal antibodies was performed. After rescanning histological and immunohistochemical preparations, combining different immunohistochemical stains, the cell density in the tumor and stromal components was calculated in preparations stained with hematoxylin and eosin and CD4. For further calculations, we used the data obtained as a result of the number of stromal cells reduced to 1 mm2 (according to the preparation stained with hematoxylin and eosin), the so-called cell density per calculated number of CD4+-stained cells (cell area × proportion of CD4+ cells in percentages). The resulting ratio is used to predict the outcome of breast cancer: if its value is ≤ 50 %, the prognosis is assessed as favorable (in which the patient’s survival is 10 years or more).
Results. In 296 (75 %) of 394 observed patients, the proportion of CD4+ T-lymphocytes in tumor stromal cells was ≤ 50 %. Over 10 years, the overall survival of patients in this group was 93 %, which is considered a statistically favorable group for breast cancer (stages T1–2, N0). In 98 (25 %) of 394 observed patients, the proportion of CD4+ T-lymphocytes in tumor stromal cells was ˃50 %. Over 10 years, the overall survival of patients in this group was 82 %, which is considered a statistically unfavorable group for breast cancer (stages T1–2, N0).
Conclusion. Our findings suggest high accuracy of our method of breast cancer prognosis based on the quantitative assessment of CD4+ T-lymphocytes in tumor stromal cells. It can be used for breast cancer prognosis in early stages (T1–2, N0).
MAMMOLOGY. CLINICAL CASE
Interest in male breast cancer is increasing every year due to the increase in the spread of this disease. However, the lack of randomized trials in male breast cancer draws the attention of specialists to this problem. Male breast cancer is 100 times less common than female. Over the past decades, there has been an increase in the disease up to 26 %. Low awareness of general practitioners, as well as the male part of the population, untimely access to specialized specialists are the reasons for the late diagnosis of the disease. Recommendations for the treatment of male breast cancer are based on the results of studies conducted in female with a similar diagnosis.
In the period from January 2015 to September 2022, 13 patients diagnosed with male breast cancer were examined and treated in the Department of Oncology and Reconstructive Plastic Surgery of the Breast of the Russian Scientific Center of Roentgenradiology, Ministry of Health of Russia. The age of patients at the time of treatment ranged from 58 to 75 years, with a mean age of 63 years. In 2 patients (15 %), stage 0 was established, in 4 (31 %) – stage Ia, in 4 (31 %) – stage IIa, in 1 (7.6 %) – stage IIb, in 1 (7.7 %) – stage IIIb, in 1 (7.6 %) – stage IIIc. Two (15 %) patients underwent neoadjuvant polychemotherapy, 6 (46 %) patients underwent adjuvant polychemotherapy. In 7 (54 %) patients, surgical treatment was performed without further adjuvant polychemotherapy. Six (46 %) patients underwent radiation therapy. Hormone therapy was prescribed to all 13 (100 %) patients. When contacting the clinic, the most frequent complaints would be the appearance of a seal behind the nipple, discharge from the nipple.
When diagnosing male breast cancer, the same methods are used as female. Tactics of treatment is determined individually. Early diagnosis of the disease and timely prescribed therapy lead to many years of remission.
GYNECOLOGY. ORIGINAL REPORTS
Background. Endometrial cancer occupies a leading position in the structure of oncogynecological pathology. According to modern literature, circulating tumor cells, which represent a heterogeneous population, participate in the processes of recurrence and metastasis. Moreover, tumor cells can form hybrid forms with blood cells, increasing their malignancy.
Aim. To conduct a comparative characterization of the features of the occurrence of atypical/hybrid forms of EpCAM+CD45+ cells in the blood of patients with endometrial cancer before and after surgery, and to assess their prognostic significance.
Material and methods. The prospective study NCT04817501 included 55 patients with newly diagnosed T1a-2N0M0 stage endometrial cancer, average age 57.8 ± 1.7 years, who were admitted for treatment at the Research Institute of Oncology, Tomsk National Research Medical Center of the Russian Academy of Sciences and/or Tomsk Regional Oncological Dispensary. At the same time, metastases and cancer recurrences were found in 11 patients out of 55 patients after 4–5 years of follow-up after treatment. The material for the study was stabilized EDTA venous blood taken from patients before surgical treatment of the tumor and on the third day after treatment. The presence of atypical/hybrid forms of EpCAM+CD45+ cells in blood serum was determined by multicolored flow cytometry using monoclonal antibodies to CD45 and EpCAM molecules labeled with various fluorochromes.
Results. When comparing the frequency of occurrence of atypical/hybrid EpCAM+CD45+ cells in patients with endometrial cancer before surgery and on the third day after surgery, no differences were found. Comparing the frequency of occurrence of atypical/hybrid forms of EpCAM+CD45+ cells in patients with endometrial cancer with hematogenous metastases and relapses and in patients with endometrial cancer without hematogenous metastases and relapses, it was found that in the blood of patients with endometrial cancer before surgery, with developed hematogenous metastases and relapses after treatment, EpCAM+CD45+ cells are more common (p = 0.03). It was found that the concentration of EpCAM+CD45+ cells in patients with established relapses and metastases of 125 (120;387) cells/ml is higher (p = 0.022) than in patients without these complications of 30 (0;220) cells/ml. During the ROC analysis, it was found that the best cut-off point for the model is the value of 80 cells/ml. The sensitivity of the model is 81.8 %, the specificity is 67.7 %. The indicator of the area under the ROC curve was 0.733.
Conclusion. The number of atypical/hybrid forms of EpCAM+CD45+ cells before treatment is associated with the risk of relapses and hematogenous metastases in patients with endometrial cancer.
Background. Endometrial cancer (EC) is one of the most significant oncogynecological problems. The main mortality cause in this disease, as in the case of other malignant neoplasms, is the tumor progression. The presence of mutations associated with mismatch repair-deficient is of great prognostic importance. Immunotargeting therapy (ITT), lenvatinib in combination with pembrolizumab, seems to be the most effective solution in the second line treatment of advanced EC without microsatellite instability. At the same time, the group of such patients is heterogeneous in terms of progression-free survival (PFS) on ITT. So that it determines the continuing need to search for reliable parameters steadily associated with the PFS duration in this type of treatment.
Aim. To analyze the clinical and morphological features in patients with advanced EC depending on the PFS duration on ITT. Materials and methods. The study included data on patients (n = 36) with advanced EC who received ITT in oncological dispensaries in Siberia and the Russian Far East. The overall patients’ group was analyzed using the Kaplan-Meier method. PFS was defined as the time from the ITT initiation until progression or death against the background of treatment. The influence of the selected factors (clinical and morphological parameters, treatment features, and adverse events) on PFS was assessed using a log-rank criterion. The study participants were then divided into 2 subgroups (15 women and 9 women) according to median PFS. Mann–Whitney tests for independent samples (quantitative measures), and Fisher’s tests (qualitative measures) were used to identify significant differences in comparison subgroups for the selected factors. Differences were considered statistically significant when the significance level was reached (p <0.05); data at the statistical trend level (p <0.10) were also discussed.
Results. In the study group, median PFS on ITT was 9.7 months (cut-off point), which was accepted as a response criterion. Among the 74 parameters reflecting clinical and morphological features in patients with advanced EC, metastatic lesions of pelvic lymph nodes (p = 0.028), para-aortic lymph nodes (p = 0.014), bone metastases (p = 0.080), and degree of estrogen receptor expression in tumor cells (p = 0.071) were associated with PFS. Partial regression as the maximal response to ITT (62.5 % vs 7.14 %, p = 0.011), as well as longer duration of response (median PFS 15.11 ± 1.10 months vs 4.47 ± 0.57 months, p = 0.00007), and the absence of foci in the pelvic/para-aortic lymph nodes (89 % vs 50 %, p = 0.069, and 89 % vs 47 %, p = 0.048, respectively), were more frequently observed in patients with a duration of median PFS ≥9.7 months compared to those with progression before 9.7 months. Stabilization as the maximum response to ITT (78.6 % vs 37.5 %, p = 0.072) was more frequently registered in the subgroup of patients with progression up to 9.7 months.
Conclusion. ITT can be considered as a potentially promising therapeutic option in advanced EC. Further research in this direction should be aimed at finding criteria to identify patients with EC who would have most benefit from this type of therapy more accurately.
Background. Transarterial chemoembolization (TACE) with drug-eluting beads has been used in the treatment of tumors of the female reproductive system complicated by bleeding. However, questions arise: how to integrate the method into the treatment regimen and at what stage should it be applied?
Aim. To evaluate the effectiveness of TACE in tumors of the female reproductive system complicated by bleeding at different stages of the disease.
Materials and methods. A retrospective analysis of 80 women with primary (group 1) and 20 with recurrent tumors (group 2) of the reproductive system, who underwent 110 TACE with drug-eluting beads “Sphere-Spectrum” (100 primary, 10 repeated), is presented. Mostly used drug-eluting beads “Sphere-Spectrum”. The indication for TACE was tumor bleeding. For dynamic control, magnetic resonance imaging of the small pelvis was performed no later than 14 days before, 14–21 days and 1–3 months after TACE.
Results. Hemostasis after TACE in all cases was achieved by the end of 1 day. There was no progression of the tumor process in any case. In group 1, 56 women (70 %) after TACE were operated on (stages 1B–2A), although according to preoperative magnetic resonance imaging staging, only 34 women (43 %) were subject to surgical treatment; 3 women underwent radiation therapy, 23 – chemoradiotherapy, systemic chemotherapy and immunotherapy in accordance with the stage of the disease. In group 2, 3 women were operated on after correction of their somatic condition and tumor reduction, 3 women underwent chemoradiotherapy, 14 women continued systemic chemotherapy.
Conclusion. TACE has shown high efficiency as a hemostatic and antitumor therapy. It should be included in the treatment regimen for women with bleeding from tumors of the reproductive system at any stage of the disease, which allows expanding the available options for antitumor therapy for this category of patients; at the same time, the use of TACE as a monomethod requires further study.
GYNECOLOGY. CLINICAL CASE
Cardiac metastasis from endometrial cancer is a very rare finding. The article presents a case of death, demonstrating the aggressive clinical course of endometrial serous carcinoma. In this clinical example the disease was accompanied by generalized metastasizing through a lymphogenous route to unexpected distant organs (peribronchial lymph nodes, pleura, pericardium).
According to various literature sources, in the general population of women with synchronous endometrial cancer and ovarian cancer is quite rare. We have not found a single foreign or domestic literary source describing clinical cases of primary multiple malignant tumors: synchronous endometrial cancer and ovarian cancer associated with pregnancy.
We present an interesting clinical example that clearly demonstrates the possibility of successful treatment of this variant of primary multiple malignant tumors – synchronous endometrial cancer and ovarian cancer associated with pregnancy. The features of the course of the disease, the features and difficulties of treatment of this pathology are shown. And also the high efficiency of the treatment was shown according to the morphological study with an assessment of the drug pathomorphosis according to Lavnikova.
A case of successful combined treatment is presented, taking into account the combined pathology. According to the received data, it is possible to conclude. The management of pregnant women and the treatment of cancer should be carried out in specialized centers with experience in the treatment of oncological diseases associated with pregnancy.
Cervical cancer is a malignant tumor originating from the mucous membrane of the cervix (ectocervix or endocervix). In 2020, 604,000 new cases of the disease were registered, with 342,000 deaths. Today, a significant rejuvenation of this pathology is recorded – the highest incidence rate occurs in the age group from 15 to 39 years.
The cause of the development of cervical cancer is the human papillomavirus of oncogenic genotypes, and in Russia, human papillomavirus types 16 and 18 are found in most patients. Risk factors: early onset of sexual activity, frequent change of sexual partners, refusal of “barrier” type contraceptives, smoking, immunosuppression, the question of the influence of various sexually transmitted infections is being discussed.
The present article describes a clinical case of performing an organ-preserving operation: laparoscopic extended trachelectomy with sentinel lymph nodes determination, urgent cytological and histological studies, with the formation of the obturator apparatus with a soft titanium nickelide implant for invasive cervical cancer in a patient with unrealized reproductive function.
Organ-preserving surgeries in patients with cervical cancer allow preserving childbearing function while maintaining oncological radicality of surgical treatment. A modern, multidisciplinary approach of an oncologist-gynecologist and a reproductologist is the basis of a modern strategy for managing a patient with cervical cancer and unrealized reproductive function.
ISSN 1999-8627 (Online)