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Background. One of the causes of complications in breast cancer patients after immediate breast reconstruction (IBR) is postmastectomy radiation therapy (PMRT).Aim. Retrospective analysis of the results of IBR, and evaluating the effect of PMRT on the frequency and type of complications.Materials and methods. Between 2015 and 2021, 798 patients underwent IBR with tissue expander or implant in N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia. PMRT was performed in 375 patients (group 1). The remaining 423 patients did not receive PMRT (group 2). Complications, including reconstructive failure (RF), Baker grade III/IV capsular contracture (CC), were recorded and analyzed.Results. Finally, cosmetic result analyzed in 521 patients. In 281 patients of PMRT group (group 1) IBR with expander or implant were performed in 144 and 137 cases, respectively. In the 240 patients without PMRT (group 2), IBR with expander was performed in 81 patients, with implant – in 159 cases. Pooled analysis revealed that overall rate of complications in the PMRT group was 33.8 % (in 95 of 281 patients), in non-irradiation patients – 22.9 % (in 55 of 240 patients), p 0.05. CC in group 1 were detected in 28 (10 %) patients, in group 2 in 11 (4.6 %) patients, p 0.2). On the contrary, CC were mentioned in 22 (16.1 %) of irradiated patient and in 8 (5 %) patients that didn’t receive PMRT, p 0.2. CC were observed in 6 (4.2 %) patients from PMRT group and in 3 (3.7 %) patients treated without PMRT, p >0.2.Conclusion. PMRT in patients after IBR with simultaneous installation of a permanent implant is characterized by a decrease in the incidence of RF, but an increase in the incidence of CC.

Background. Three-dimensional automated breast ultrasound (ABUS) is an innovative technology that allows global visualization of the breast and eliminates the operator-dependence of hand held ultrasound. Three-projection scanning during ABUS is provided by an ultra-long (15.4 cm) probe with a frequency of 14–16 MHz, and then the slices are reconstructed on a workstation. At the same time, high-frequency converters create high-resolution images. Through a special coronal projection, ABUS identifies variants of minimal, non-palpable breast cancer, including those with women with high mammographic breast density, which makes it a promising additional (supplemental screening) method of oncomammoscreening.Aim. To assess the use of ABUS as a supplemental screening tool in women with high mammographic breast density.Materials and methods. The study was conducted in 2018 at the N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia. As part of the study, 192 women underwent mammography, ABUS, and multiparametric ultrasound (B-mode, color Doppler, elatography) in standard manual mode.Results. In the course of the study, in 192 patients, mammography revealed 42 cases of breast cancer, while using the AUS and manual ultrasound, additionally were identified 9 cases of breast cancer. Also, the ABUS showed high accuracy in assessment of the distribution of breast cancer – multifocal, multicentric and bilateral.Conclusion. ABUS is a promising and highly effective diagnostic method in women with high mammographic breast density, with its advantages and disadvantages, which can be used in combination with mammography as a supplemental screening tool, especially in women at high risk of developing breast cancer.

This paper proposes and analyzes a mathematical model of tuberculosis and HIV co-infection that specifies for Russian Federation regions, based on mass balance law and described by eight ordinary differential equations. A sensitivity-based identifiability analysis of this mathematical model was performed, which revealed the sensitivity of the averaged parameters of the models to statistical real data of infectious individuals based on the Sobol method. The problem of identifying the sensitive epidemiological parameters (contagiousness, the rate of tuberculosis activation, additional mortality rate, etc.) for the model was reduced to the problem of minimization of the quadratic misfit function. The numerical results of the modeling of the number of people expected to be infected with tuberculosis and HIV were shown and discussed for the Sverdlovsk and Moscow regions of the Russian Federation. It has been shown that increasing the capacity of the medical system by 10% will make it possible to reduce the number of diagnosed cases of active tuberculosis by 2 times over the next 3 years in some regions of Russian Federation.

BRCA-associated triple-negative breast cancer (TNBC) is characterized by high sensitivity to DNA-damaging cytotoxic drugs. The use of well-known BRCA1/2-specific antitumor agents – platinum derivatives and PARP inhibitors – has been discussed for a long time in the context of the treatment of metastatic BRCA-associated TNBC. Neoadjuvant regimens based on the use of anthracyclines and taxanes are the standard of drug therapy for primary BRCA-associated breast cancer. At present, there are few data regarding the addition of platinum drugs to anthracycline-taxane neoadjuvant chemotherapy in the treatment of primary BRCA-associated TNBC. This review details the various treatment options for both primary and metastatic BRCA-associated TNBC. It has been shown that the development of new strategies for the neoadjuvant chemotherapy of patients with primary BRCA-associated TNBC is an urgent clinical need to reduce the risks of recurrence and progression.

Background. Breast cancer is the main cause of morbidity and mortality of the female population among economically developed countries, including in Russia. Despite the continued increase in morbidity, mortality is decreasing, which is confirmed by a decrease in the index of accuracy (the ratio of the number of deaths to the sick). Calculations of survival at the population level (the most important criterion for evaluating the activities of the oncological service) in Russia are carried out only on the basis of databases of the population cancer registry of the North-Western Federal District. The accumulated 1.5 million primary cases of malignant tumors allowed for the in-depth development of data on rare tumor localities, including breast cancer among the male population.Aim. To study the impact of the coronavirus pandemic on the dynamics of the process of detection, mortality and survival of breast cancer patients in Russia and in the North-Western Federal District of the Russian Federation.Materials and methods. The material of the study is the reference books of the P. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiology Center, Ministry of Health of Russia, and the N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia, and the database of the population cancer registry of the North-Western Federal District, clinical materials of the surgical department of breast tumors of theN.N. Petrov National Medical Research Oncology Center. More than 110 thousand primary cases of breast cancer were selected. Data processing was carried out by standard methods of oncology statistics recommended by the International Association of Cancer Registries (Eurocare program).Results. A significant impact of the coronavirus pandemic on the primary registration of breast cancer in Russia from 2019 to 2020 has been established, with some weakening of its impact in the subsequent period. The pandemic has had a significant impact on the quality of primary registration of patients. The value of the index of accuracy has been set back five years, but there is a sign of its improvement in 2021. The positive dynamics of one-year and five-year survival of patients with breast cancer is shown. The quality of registration of patients with breast cancer by detailed localization and histological structures of breast cancer was investigated. A significant decrease in the mortality of patients was noted when studying the patterns of dynamics in annual mortality over three follow-up periods.Conclusion. A steady increase in the incidence of breast cancer among women has been established, and the negative impact of the coronavirus pandemic has been noted. The mortality rate of the Russian population from breast cancer continues to decrease. The localization and histological structure of the incidence of breast cancer in women remains unchanged. The one-year and five-year survival rate of breast cancer patients continues to grow.

New epidemics encourage the development of new mathematical models of the spread and forecasting of infectious diseases. Statistical epidemiology data are characterized by incomplete and inexact time series, which leads to an unstable and non-unique forecasting of infectious diseases. In this paper, a model of a conditional generative adversarial neural network (CGAN) for modeling and forecasting COVID-19 in St. Petersburg is constructed. It takes 20 processed historical statistics as a condition and is based on the solution of the minimax problem. The CGAN builds a short-term forecast of the number of newly diagnosed COVID-19 cases in the region for 5 days ahead. The CGAN approach allows modeling the distribution of statistical data, which allows obtaining the required amount of training data from the resulting distribution. When comparing the forecasting results with the classical differential SEIR-HCD model and a recurrent neural network with the same input parameters, it was shown that the forecast errors of all three models are in the same range. It is shown that the prediction error of the bagging model based on three models is lower than the results of each model separately.

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 (

Background. BRCA-associated triple negative breast cancer (TNBC) is considered one of the most aggressive subtypes of breast cancer with high sensitivity to chemotherapy, which leads to increased interest in finding new treatment options for patients with this subtype of breast cancer. Aim. To determine the role of adding a platinum drug to standard systemic neoadjuvant therapy (NAC) for patients with primary BRCA-associated TNBC with clinical stage T1–3N0–3M0, and to evaluate the effect of platinum-based drugs on recurrence-free survival in patients of this category. Materials and methods. The study included 75 patients diagnosed with primary BRCA-associated TNBC. They were divided into 2 groups depending on the NAC provided, and then they were subdivided depending on the completion of the course of ongoing NAC, the final pathomorphological result and the presence of recurrence. Results. Group I included 48 (64 %) patients who received the AC–T regimen; in group II (n = 27 (36 %)) patients received NAC according to the AC–TCarb regimen. Patients of group II showed a higher frequency of achieving pathological complete response (pCR) compared with patients of group I (73.7 % versus 41.2 %, respectively, p = 0.0433). Taking into account the NAC regimens being carried out, patients of group I had a slightly higher risk of recurrence compared to patients of group II (p = 0.099). Conclusion. In patients with primary BRCA-associated TNBC, the addition of platinum compounds to the systemic NAC resulted in achieving of pCR in 73.7 % cases compared with 41.2 % pCR after the standard anthracycline-taxane NAC, which entails a reduced risk recurrence in this category of patients. Performing a full course of planned NAC has a positive trend in achieving pCR in patients of this category.

Background. Surgery is fundamental in complex and combined approach in the treatment of the early breast cancer. It is a common fact, that absence of tumor cells in the resection margin is the main indicator of oncological safety of the breast-conserving surgery (BCS). The presence of tumor cells in examined margin is the predictor of local recurrence after BCS for breast cancer. Currently the clinical need for precise and fast method of intraoperative assessment of the resection margin status is kept. Intraoperative evaluation of the resection margin with the usage of digital two-point sectorography (Faxitron PathVision) appeared as the alternative to intraoperative histological examination, providing the optimum size of the information about adequacy of the carried out surgical treatment.Aim. To evaluate diagnostic features of the digital two-point sectorography Faxitron PathVision in the intraoperative assessment of the resection margin status after the surgical treatment in comparison with planned histologic examination.Materials and methods. 368 conducted conservative surgeries were analyzed; patients were divided in two groups depending on neoadjuvant chemotherapy. The first group of patients included 236 patients, who didn't receive neoadjuvant chemotherapy before surgery; second group included 132 patients, who received neoadjuvant chemotherapy. Subset analysis of detection rate of the positive resection margin (R1) was carried out with the usage of the intraoperative assessment of the resection margin on the X-ray device Faxitron PathVision or without this method. After each BCS resection margin status was assessed on planned histologic examination for the presence of the tumor cells, with subsequent analysis of the frequency of reoperations when R1 was found.Results. In 368 tested surgical specimens after BCS R1 was found in 25 cases, which is 6.8 %. From 236 patients in the first group after BCS R1 was found in 20 cases, which is 8.5 %; from 132 conducted operations in the second group in 5 (3.8 %) cases the presence of R1 is found. Reoperations were performed in 13 cases and tumor cells were found in 3 cases in the sub-group which didn't receive intraoperative assessment with X-ray device Faxitron PathVision.Conclusions. Assessing the results of our study we can make a conclusion about the positive experience of performing BCS and intraoperative evaluation of the resection margin with the usage of the digital two-point sectorography (Faxitron PathVision) and low frequency of R1 (3.8 %) in comparison with absence of this method (8.5 %).

Background. Achieving a pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) is a predictive factor for improving disease free and overall survival. In triple negative (TN) and HER2-positive breast cancer (BC), the pCR rate exceeds 60 %. Patients with TN and HER2-positive BC who demonstrate an excellent response to NST are like­ly ideal candidates for downsizing surgery. The condition for reducing the volume of surgical intervention is a reliable determination of pathologic complete response using instrumental imaging and biopsy methods.Aim. To further assess the accuracy of post-NST image-guided biopsy to predict pCR.Materials and methods. Sixty one patients with T1-3N0-3 triple negative or HER2-positive BC receiving NST in the Department of Breast Tumors of the NMRC of Oncology named after N.N. Petrov in the period from 2017 to 2019 were enrolled in this single-center retrospective trial. Patients underwent ultrasound-guided core-biopsy of the initial breast tumor region before surgery. Findings were compared with findings on pathologic evaluation of surgical specimens to determine the performance of biopsy in predicting pCR after NST.Results. After neoadjuvant systemic therapy, clinical partial response (cPR) was diagnosed in 47 (77 %) patients, clinical complete response (cCR) in 14 (23 %) patients. pCR in the core-biopsy tissue and surgical material was achieved in 46 (75.4 %) and 37 (60.7 %), respectively. Performance of image-guided core-biopsy: sensitivity 100 % (95 % confldence interval (CI) 90.51-100), specificity 62.5 % (95 % CI 40.59-81.20), false-negative rate (FNR) 0 %, positive-pre­dictive value (PPV) 75.00 % (95 % CI 59.46-85.99), negative predictive value (NPV) 100.00 %.Conclusion. This retrospective trial showed that ultrasound-guided core biopsies are accurate enough to identify breast pCR in patients with triple-negative or HER2-positive BC with good response after NST (FNR 0 %). Based on these results, a prospective clinical trial has commenced in which breast surgery is omitted in patients with a breast pCR after NST according to image-guided biopsy.

Background. The accurate and early diagnosis of breast cancer can improve efficacy of the treatment. The standard diagnostic methods such as mammography, ultrasound, and magnetic resonance tomography have a pivotal role in the detection of breast tumors, however, in some cases, they have low diagnostic accuracy. Mammoscintigraphy (MSG) / molecular breast imaging (MBI) with tumor-specific radiopharmacy 99mTc-Technetril in patients with breast cancer can considerably increase the accuracy of diagnosis. However, the diagnostic performance of MSG / MBI in the detection of different biological subtypes of breast cancer is still under investigation.Aim. To evaluate the accuracy of MSG / MBI with 99mTc-Technetril in diagnosis of different biological subtypes of breast cancer.Materials and methods. The analysis included the results of MSG / MBI of 1080 patients (2154 mammary glands), who were examined for suspected breast cancer. MSG / MBI were performed 5–15 min after intravenous injection into the vein of one of the feet of 370–740 MBq of tumor-specific radiopharmacy 99mTc-Technetril. Examinations performed from 2007–2020 was carried out on the emission computed tomography Forte (Philips); since 2020 the molecular visualization has been providing on the special gamma-camera Discovery NM750b (General Electric). The obtained data were evaluated by 2 experienced radiologists. Verification of changes in breasts was provided by morphological examination (1060 cases) or dynamic observation.Results. The sensitivity, specificity and overall accuracy of MSG / MBI were 90 %, 98 %, 95 % correspondingly. When diagnosing tumors with a diameter of up to 10 mm, the sensitivity of MSG / MBI was decreased to 83 %. In patients with various biological subtypes, the sensitivity of MSG / MBI was as follows: luminal A – 88 %; luminal B– – 91 %; luminal B+ – 92 %; triple negative – 93 %; HER2-positive – 96 %. The intensity of tumor uptake depended on the biological subtype of breast cancer. The average values of the 99mTc-Technetril uptake coefficient were as follows: luminal A – 1.59; luminal B– – 1.71; luminal B+ – 1.95; triple negative – 1.93; HER2-positive – 2.22.Conclusion. Retrospective analysis indicate high diagnostic performance of MSG / MBI: sensitivity – 90 %, specificity – 98 %, accuracy – 95 %. There are significant differences in the intensity of 99mTc-Technetril accumulation in tumors in patients with different biological subtypes of breast cancer (p = 0.01–0.004). MSG / MBI characterized by significant differences in the sensitivity in the diagnosis of luminal A and HER2+ breast cancer subtypes: 88 % and 96 %, respectively (p = 0.02).

Intro: Study goal. To build a SEIR-model for predicting the HIV/tuberculosis coinfection (HIV/TB) epidemic for Russian territories with low TB burden Study goal. Predicting the HIV/TB epidemic for Russian territories with low TB burden Methods: A quantile ranking of territories (at 0.33 and 0.66 levels) was made for regions Russia (incidence and mortality from TB). Regions at the bottom 30% indicators over the entire observation period (2010-2020) were assigned a low incidence and mortality rate. The description of the dynamics of TB and HIV coinfection was based on the SEIR model, which is characterized by a system of ordinary differential equations. Incidence data for 2010-2017 were used to build the model, data for 2018-2020 were used to test it. The model is implemented in the Python programming language. Findings: 11 regions with low morbidity and mortality from tuberculosis were identified. To build a model in each region, the population was divided into the following groups: S – susceptible non-immunized population; L – patients with latent TB (LTB); I – patients with active TB; T – population cured from TB; J1 – HIV infected individuals; J2 – infected with HIV and LTB; J3 – infected with HIV and active TB; A – AIDS patients. Graphs of the population groups vs. Time dependence for each territory were plotted. The results obtained in the SEIR model graphs of the number of HIV/TB infected and TB patients are similar to real-world data. Discussion: The study results will help predict the direction of the epidemic process HIV/TB, the number of diseased and recovered individuals in the next 3-5 years and allows estimating workload on the health system in each time period. Conclusion: The study yielded the SEIR model that can be used for short-term prediction of the epidemic of HIV/TB in the Russian territories with low TB burden.

Immuno-oncology is a rapidly developing field in medicine. Drug combination therapies have already been studied in many clinical trials on various tumor types. In recent years, a checkpoint inhibition therapy with monoclonal antibodies targeting PD-1 and its ligand PD-L1 has been developed. Breast cancer had been examined in the field of immune-oncology relatively recently. This review focuses on clinical evidence regarding immune checkpoint inhibition for curative treatment of various breast cancer subtypes. In addition, we present the results of studies demonstrating the prognostic and predictive value of levels of tumor-infiltrating lymphocytes (CD4 and CD8), their quantitative ratios, and their correlation with regulatory genes (PD-1, PD-L1, and FOX-P3).

This paper uses Covasim, an agent-based model (ABM) of COVID-19, to evaluate and scenarios of epidemic spread in New York State (USA) and the UK. Epidemiological parameters such as contagiousness (virus transmission rate), initial number of infected people, and probability of being tested depend on the region's demographic and geographical features, the containment measures introduced; they are calibrated to data about COVID-19 spread in the region of interest. At the first stage of our study, epidemiological data (numbers of people tested, diagnoses, critical cases, hospitalizations, and deaths) for each of the mentioned regions were analyzed. The data were characterized in terms of seasonality, stationarity, and dependency spaces, and were extrapolated using machine learning techniques to specify unknown epidemiological parameters of the model. At the second stage, the Optuna optimizer based on the tree Parzen estimation method for objective function minimization was applied to determine the model's unknown parameters. The model was validated with the historical data of 2020. The modeled results of COVID-19 spread in New York State and the UK have demonstrated that if the level of testing and containment measures is preserved, the number of positive cases in New York State remain the same during March of 2021, while in the UK it will reduce.

Background. Breast cancer (BC) can be unifocal, multifocal, multicentric (MCBC) and bilateral according to number and localization of tumors. MCBC has different clinical and biological characteristics compared to unifocal BC, for example, a higher risk of lymph node involvement, a more aggressive natural history and a worse prognosis. Therefore, accurate diagnosis and detection of MCBC is one of the main tasks of imaging.Objective: to compare diagnostic accuracy of contrast enhanced spectral mammography (CESM) and digital mammography (DM) in the diagnosis of MCBC.Materials and methods. The study included 438 women with suspected BC. The results of DM and CESM were compared with the results of a pathomorphological study performed after surgery or biopsy to assess the effectiveness of imaging modalities. DM was performed for all women using a Senographe DS (GE, USA) unit. CESM was performed after intravenous injection of non-ionic contrast agents using injector with breast compression in the craniocaudal and mediolateral projections. The study was performed for both glands regardless of the location of the suspicious lesion in order to timely diagnose clinically asymptomatic bilateral cancer. The final diagnosis was made based on the results of the pathomorphological examination. MCBC was diagnosed when two or more tumors at a distance of 3 cm or more from each other were detected. Visualization of additional grouped calcifications of malignant type occupying a small portion of breast tissue (more than 15 pieces per 1 sq. cm) was considered as another mammographic sign of MCBC.Results. According to the pathomorphological examination BC was diagnosed in 154 (35 %) women out of 438 examined patients. MCBC was identified in 25 (16 %) of 154 patients. CESM was more effective than DM in detecting MCBC with sensitivity of 88.0 % vs 48.0 % (p = 0.002), accuracy of 92.2 % vs 90.9 %, negative predictive value of 97.6 % vs 90.8 % (p = 0.02), respectively. But the specificity was significantly higher in DM than in CESM – 99.2 % vs 93.0 % (p = 0.009), respectively, and the positive predictive value did not differ significantly (p = 0.12).Conclusion. CESM is a more sensitive method for diagnosing MCBC compared to DM with sensitivity of 88.0 % vs 48.0 %. The high negative predictive value of CESM (97.6 %) confirms the fact that this modality is an effective method for planning surgery and radiation therapy.

Objective: to compare the immediate and long-term outcomes of patients with early breast cancer treated with intraoperative radial therapy depending on the biological subtype of breast cancer.Materials and methods. We prospectively evaluated number of recurrences, cosmetic effect and early treatment results of 104 patients with early breast cancer aged 66.72 ± 0.68 years old. The mean follow-up period was 36 months. The mean dose on the surface of applicator was 17.8 Gy, on the depth 0.5 cm – 8.8 Gy, on the depth 1.0 cm – 5 Gy. The mean time of radiation was 22.15 min ± 28.09 sec.Results. The local recurrence was in 3 patients. The first patient had triple negative breast cancer subtype, the second patient had luminal B HER2+, and the third one had luminal B HER2– subtype. Relapses occurred in 7, 14 and 20 months after the end of treatment respectively. The recurrence rate in patients with luminal B biological subtype was 10.71 %; in patients with triple negative subtype was 20 %. All recurrences were found in the area of the postoperative scar.Conclusion. The obtained results question the rationale for the use of the demonstrated method in patients with luminal B and triple negative molecular subtypes of tumors.

The article discusses modern approaches in the treatment of HER2-positive breast cancer (BC) with brain metastases (BM).The patients are subject to multidisciplinary, comprehensive and biologically – oriented treatment, with the involvement of a neurosurgeon and a radiation therapist to make a decision considering local treatment of BM, as well as a clinical oncologist to choose systemic drug therapy. Local treatment of HER2+ BC with BM patients includes surgical treatment and/or radiotherapy. Use of targeted anti-HER2 therapy changes “biology” of the disease from aggressive to indolent.In the prospective KAMILLA trial, clinically significant antitumor activity of trastuzumab emtansine was found for the first time both in patients with HER2+ BC with BM, who were previously treated with radiotherapy, and without radiotherapy in the anamnesis, which suggests the validity of further use of trastuzumab emtansine in this category of patients.The antitumor activity of trastuzumab emtansine in patients with HER2+ BC with BM was also confirmed in preclinical models. Despite the similar drug distribution in the tissues, trastuzumab emtansine, in contrast to trastuzumab, significantly slowed the growth of metastases, causing the induction of apoptosis in HER2+ BC models with BM in mice.

Immuno-oncology is a rapidly developing field in medicine. Drug combination therapies have already been studied in many clinical trials of different types of tumours. In recent years, a checkpoint inhibition therapy with monoclonal antibodies that target cytological T-lymphocytes has been developed. Thus, inhibition of two regulator genes CTLA 4 and PD1 or PD-L1 ligand to it is able to restore mediated T-cell tumour regression in its many localizations. The article considers a number of key fields of immunology and immunotherapy through a specific example of breast cancer (BC): the role of T-lymphocytes, vaccines, biomarkers of immunotherapy. The treatment used by the authors was based on an innovative technology of autologous dendritic cell-based vaccine based on highly immunogenic cancer/testis antigens (CTA) for immunotherapy of malignant tumours. The technology of specific CTA+-activated autologous dendritic cells (DC)-based immunotherapy was chosen as an innovative solution for the treatment of breast cancer patients. The treatment results showed that a clinically significant anti-tumour effect was achieved in 73.7% of patients. Median disease-free survival was 8.3 months (95% Cl 6.5-9.9 months), no grade 3-4 complications were recorded, grade 1-2 complications were observed in 57% of patients. The immunological effect in laboratory tests was recorded in 92% of patients. Thus, autologous DCs loaded with cancer/testis antigens can be considered as palliative dendritic vaccine therapy in patients with metastatic breast cancer who have exhausted standard treatment options. Also, the authors presented the results of immunological studies of the prognostic and predictive significance of the immunological response from the perspective of pathomorphology and general immunology, including tumour-infiltrating T-lymphocytes (TILs, CD3, CD4, CD8), their quantitative ratio and correlation with regulatory genes (PD-1, PD- L1, FOX-P3). The results of overall analysis comprising data of 2,148 patients from 9 centers confirmed the strong prognostic role of stromal tumour-infiltrating lymphocytes (sTILs) in early triple-negative breast cancer.

The paper presents the results of sensitivity-based identif iability analysis of the COVID-19 pandemic spread models in the Novosibirsk region using the systems of differential equations and mass balance law. The algorithm is built on the sensitivity matrix analysis using the methods of differential and linear algebra. It allows one to determine the parameters that are the least and most sensitive to data changes to build a regularization for solving an identif ication problem of the most accurate pandemic spread scenarios in the region. The performed analysis has demonstrated that the virus contagiousness is identif iable from the number of daily conf irmed, critical and recovery cases. On the other hand, the predicted proportion of the admitted patients who require a ventilator and the mortality rate are determined much less consistently. It has been shown that building a more realistic forecast requires adding additional information about the process such as the number of daily hospital admissions. In our study, the problems of parameter identif ication using additional information about the number of daily conf irmed, critical and mortality cases in the region were reduced to minimizing the corresponding misf it functions. The minimization problem was solved through the differential evolution method that is widely applied for stochastic global optimization. It has been demonstrated that a more general COVID-19 spread compartmental model consisting of seven ordinary differential equations describes the main trend of the spread and is sensitive to the peaks of conf irmed cases but does not qualitatively describe small statistical datasets such as the number of daily critical cases or mortality that can lead to errors in forecasting. A more detailed agent-oriented model has been able to capture statistical data with additional noise to build scenarios of COVID-19 spread in the region.

Objective: to compare cosmetic result of two techniques of boost delivery to the tumor bed after breast concerving treatment.Materials and methods. A retrospective analysis of the results of treatment of patients with stage IA–IIIA breast cancer from three groups was carried out: 1) 45 women received tumor bed boost with interstitial brachytherapy; 2) 48 women with electrons (energies from 6 to 18 MeV); 3) 59 women did not receive additional irradiation of the removed tumor bed. The analysis of the cosmetic results of treatment was carried out using subjective and objective methods using mammographic data, including information about the most common complications from the skin, subcutaneous fat and remaining breast tissue, such as telangiectasias, fibrosis, and fatty necrosis.Results. According to the results of self-assessment by patients and assessment by independent expert (oncologist), carried out on a 4-point Harvard scale, the cosmetic result in most cases was characterized as “excellent” or “good”. Frequency and grade of telangiectasia were used for objective evaluation of skin complications and were similar in all 3 groups. The incidence of localized fibrosis also did not differ and was most often observed as absent or moderate (grade 1–2). There were no significant differences between the severity and incidence of fatty necrosis on both physical examinations and when it was evaluated on mammography.Conclusions. additional irradiation of the tumor bed does not compromise cosmetic result of the treatment. In most cases (57–78 %) estimated as “good” and “excellent”. The cosmetic result of the treatment does not depend on the technology of boost delivery.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.

Introduction This article describes a clinical case of a stress fracture of the distal tibial metaepiphysis following a high-energy tibial shaft fracture stabilized with interlocking intramedullary (IM) nail to identify an underlying cause of the traumatic event. Objective To demonstrate the occurrence of a stress fracture after adequate interlocking IM nailing of a traumatic fracture due to systemic osteoporosis that presented no clinical manifestations prior to injury. Material and methods Magnetic resonance imaging was performed to diagnose the stress fracture. Bone mineral density and laboratory markers of bone metabolism were measured to identify underlying causes of the stress fracture. Consolidation of the traumatic fracture fixed with interlocking IM nail was re-evaluated with a radiograph of the fracture site. Results The stress fracture was seen off the IM nail on MRI scans. Osteoporosis was diagnosed with bone densitometry using dual energy X-ray absorptiometry, and deoxypyridinoline, a bone resorption marker and vitamin D deficiency were identified with laboratory tests. No signs of fracture union were seen radiologically. Conclusion A stress fracture of the distal tibial metaepiphysis detected 3 months after a tibial shaft fracture fixed with interlocking IM nail can be considered an insufficiency fracture caused by primary (idiopathic) systemic osteoporosis that was asymptomatic prior to the high-energy injury.

Additional covering of the lower pole with allomaterial or its synthetic analogues during immediate breast reconstruction is being performed at the N. N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia, for last 7 years. Initially, epidermal flap was the only option for lower pole coverage; later acellular dermal matrix was used as part of clinical approbation. Average complication rate ranges from 20–35 % due to blood circulatory (supply) disorders.Since 2018, a titanised mesh been used as an additional coverage of the lower pole in the department of breast tumors. Through coating characteristics and its structure the frequency of fatal complications significally decreased.

The relevance: more than 60% of cases are due to early breast cancer (EBC). Priority is the treatment of patients with early breast cancer, provided that the maximum quality of life (QL) is maintained. During or after complex treatment, more than half of patients with EBC report the occurrence of functional disorders that reduce the QL. Aim: to evaluate the event-free survival rate (EFS) of EBC patients undergoing rehabilitation within the framework of a biopsychosocial approach in the course of complex antitumor treatment. Materials and methods: the study involved 228 patients with EBC who received complex treatment from 2015 to 2019. In the prospective part of the study, 114 patients were subjected to rehabilitation measures in the framework of a biopsychosocial approach that considers both biological features of functional restriction and psychosocial disorders, a multidisciplinary team of specialists worked with all patients. In the control group, 114 patients were selected retrospectively and underwent physical and psychological rehabilitation as prescribed by a doctor. Patients of both groups are divided into subgroups depending on the availability of preoperative chemotherapy. Event-free survival was assessed over a 2-year follow-up period. Events were accepted as censored events: relapse, metastases, the occurrence of another cancer, a new concomitant disease, an exacerbation of concomitant pathology, and death. Results: Rehabilitation measures within the framework of the biopsychosocial model improve the indicators of EFS in patients with EBC. The use of a biopsychosocial approach in rehabilitation increased EFS by 3.8 months. The results of multivariate analysis, reducing the risk of occurrence of the event EBC patients undergoing rehabilitation within the framework of the biopsychosocial approach in the presence of neoadjuvant chemotherapy was 28%, in patients of younger age group (25–44 years) was 29%, in patients in menopause – 25%.

Achieving a pathologic complete response as a result of neoadjuvant treatment is associated with improved prognosis in breast cancer. The CREATE-X trial showed a significant survival improvement with capecitabine treatment of patients with residual invasive disease following neoadjuvant chemotherapy, and the KATHERINE trial demonstrated a significant benefit of trastuzumabemtansine (TDM1) in patients with HER2-positive breast cancer who did not achieve a pathologic complete response, so we have a lot of interesting alternatives of post-neoadjuvant treatments for high-risk patients. The discovery of molecular markers of resistance to endocrinotherapy (cyclin-dependent kinases (CDK 4/6), ER mutation (ESR1), mTOR signaling pathway, co-expression of ER+/HER2+) and inhibitors to them expanded the possibilities of endocrinotherapy not only in advanced and metastatic breast cancer, but also in residual ER+ tumors. The pCR rates in hormone receptor-positive breast cancer after neoadjuvant chemotherapy are around 10%, which is much lower than the values observed in HER2-positive and triple negative subtypes, so new strategies are needed to improve pCR rates in this subgroup, even though the adjuvant endocrine therapy impacts significantly the outcomes of this patients. The cyclin-dependent kinases (CDKs) are serine–threonine kinases that regulate cell cycle progression from the G1 to the S-phase during mitosis. CDKs activity can be abnormally increased or dysregulated in breast cancer, leading to a constant stimulus for cell proliferation and survival, which is a known mechanism of resistance to endocrine treatment. The CDK inhibitors act on CDKs and block their activity, thereby restoring the cell cycle regulation. In studies with metastatic hormone receptor-positive breast cancer patients, the combination of a CDKis with first or second-line endocrine therapy showed significant improvements in progression-free survival and response rates. Evolving techniques such as next-generation sequencing and gene expression profiles have improved our understanding of the biology of residual disease and also the mechanisms involved in treatment resistance.

Biopsy of signal (sentinel) lymph nodes (LN) has been performed at the N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia, for almost 20 years. In the first few years, contrast-visual method (1 % blue isosulfan and triphenyl methane control) was used in 640 patients with early (T1–2N0M0) breast cancer. In 150 patients from this cohort, standard axillary dissection was performed irrespectively of the results of signal (sentinel) biopsy. The rate of false positive responses varied between 4.6 and 6.6 %. Since 2012, radioisotope method of visualization of signal LN with intratumor administration of 99mТс-technephyte colloid particles has been used (in 708 patients with T1–3N0M0 breast cancer). This type of signal LN biopsy had the following diagnostic characteristics: sensitivity was 58.9 %, specificity was 96.2 %, diagnostic accuracy was 87.1 %.In parallel with this study, in 2016 a study of diagnostic accuracy and safety of biopsy of axillary LN after neoadjuvant systemic therapy was started. The study included 263 patients with T1N1–3M0, T2–3N0–3M0, T4N0–1M0 breast cancer. To evaluate clinical status of axillary LN, ultrasound, single-photon emission computed tomography, mammography at baseline and after completion of neoadjuvant chemotherapy ± targeted therapy (trastuzumab) were performed. In some patients, in the recent years a double method of signal LN labeling (radioisotope and fluorescent methods) was used.In patients with baseline cN+-status, the rate of false positive signal LN biopsy conclusions was 13.6 %, in patients with baseline cN0-status it was 7.7 %.The study of double contrast of axillary LN and targeted label of metastatic LN prior to neoadjuvant systemic therapy continues. In total, various modifications of biopsy of signal LN were performed in 2,000 patients with breast cancer.The study protocol was approved by the biomedical ethics committee of N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia.All patients gave written informed consent to participate in the study.

Background. The development of effective methods for diagnosing multicentric breast cancer patients (BC) is of great clinical importance, because it determines the tactics of surgical and radiation treatment.The aim of study: to compare diagnostic accuracy of scintimammography (SMG), digital mammography (MMG) and ultrasound (US) in the diagnosis of multicentric BC.Materials and methods. 410 women with histologically confirmed BC were included in this analysis. SMG was performed with dual detector SPECT unit Forte (Philips, Netherlands). Mammographic digital images were obtained on Senographe DS unit (GE Healthcare, USA). In 319 of 410 evaluated women we were able to determine results of preoperative US with high-frequency (7—18 MHz), high resolution linear array transducer. The pathological report was used as the gold standard. Multicentric BC was defined as 2 or more distinct invasive tumors occupying more than one quadrant. Detection of additional grouped calcifications of malignant type occupying a small portion of breast tissue (more than 15 pieces per 1 sq. cm) was considered as another mammographic sign of multicentric BC.Results. According to histopathological examinations multicentric BC was diagnosed in 51 of 410patients. SMG was more effective than MMG in detecting multicentric BC: sensitivity — 84.3 % vs 54.9 % (p

Objectives: To find residential areas with high incidence rate of tuberculosis in Moscow using spatio-temporal analysis of incidence data. Methods: We analyzed the spatial patterns of residence locations of smear or culture positive patients with pulmonary tuberculosis in Moscow. To identify clusters with high local incidence rates, the neighborhoods of detected cases were studied. We assessed the spatial and temporal stability of clusters. Results: For 19 033 cases diagnosed with smear or culture positive pulmonary tuberculosis among residents of Moscow in 2000–2015 we identified 18 small-scale clusters of increased incidence rate responsible for 3% of all registered cases identified on a territory inhabited by only 1% of the population. Locations of clusters were sufficiently stable in space throughout the whole period. The local incidence rate inside clusters was significantly (3–4 times) higher than the city average during the whole observation period. The presence of clusters was associated with the incidence rate in the surrounding area. Socio-demographic characteristics of patients in clusters were not significantly different from the average characteristics of patients in the city. Conclusions: The detected small-scale clusters of increased incidence may be used to target active case finding for tuberculosis. The causes and mechanisms of cluster formation and stability need further study. Keywords: Epidemiology, Spatial analysis, GIS, Resident population, Local infection, Urban