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This article provides a review of studies analyzing the etiology, diagnosis, and treatment of Peitz–Jeghers syndrome, as well as the risk of cancer of different locations in patients with this genetic disorder. We report a case of Peitz–Jeghers syndrome associated with breast cancer in young women in two generations (mother and daughter). Despite specific clinical manifestations (multiple hamartomatous polyps developing in childhood and ink-black mucous pigmentation in the woman and her immediate relatives), Peitz–Jeghers syndrome was diagnosed only after breast cancer development and consultation with oncologists. This confirms the need for informing both oncologists and general practitioners about this genetic disorder.

The retrospective study of clinical data, risk factors, and results of treatment of a large group of patients with primary systemic anaplastic large-cell lymphoma (ALCL) (n = 42) with the Т-/О phenotype is presented. Primary systemic ALCL occurred in young persons aged less than 30 years. A group of patients with its poor course (with complete remission (CR) being achieved) showed a trend for the prevalence of the signs that were a part of the standard (International Prognostic Index — IPI) factors and ones of poor prognosis, which were additionally analyzed by the authors. Significant differences in a group of patients with a good prognosis (with CR being achieved) were obtained only in the following indices: ALK protein expression (substantiating the further division and study of a homogenous group of patients), the stage of the disease, evaluation of the patients’ general condition by the ECOG scale, and the presence of B-symptoms.According to the data available in the literature, ALK-positive ALCL has a better prognosis than ALK-negative ALCL. The results given in this communication additionally confirm and extend these observations. There is evidence that, by using the IPI and the baseline prevalence of the disease, one may predict an outcome in the homogenous group of patients without CR being achieved after first-line therapy. Analysis of the findings has established no clinical risk factors associated with the baseline site of a tumor process, which influence long-term results, but this matter should be studied in further prospective investigations, by keeping in mind the location zones characteristic of ALCL.

In given article non-Hodgkin lymphomas epidemiology, main attempts of gastrointestinal tract (GIT) lymphomas sistematization, basic methods of stomach NHL diagnostics, such as radiologic and endoscopic are described. Also importance of modern endoscopic diagnostics methods is discussed: chromogastroscopy, magnifying and narrow spectral endoscopy. Morphological confirmation problems of neoplasm histologic structure using forceps biopsies during endoscopic examination are noted; possibilities of expanded procedures taking a sample, such as endoscopic resection mucous and submucosal layers are described. Possibilities and importance of endosonography both in diagnostics and in differentiation of NHL and a various malignant and non-malignant stomach pathology are in detail described.

Background. The role of neoadjuvant chemotherapy (NACT) in luminal HER2-negative breast cancer (BC) remains highly controversial due to the lack of reliable predictors of drug therapy efficacy.Objective: to evaluate the effectiveness of NACT in patients with aggressive luminal HER2-negative BC and to compare modern systems for assessing the pathomorphological response.Materials and methods. The tumor response to NACT regimens was assessed in 64 patients with aggressive luminal HER2-negative BC stage II–III. The median age of women was 46.5 years (range 31–76 years), 76.6 % had primary operable stages (cT1–3N0–1), locally advanced BC (cT4, cN2–3) – 23.4 % patients. The characteristics of BC were as follows: invasive ductal carcinoma (76.6 %), grade G2 and G3–54.7 % and 45.3 %, Ki-67 ranged from 20 % to 98 %, median 45 %. The ER expression level was low (1–10 %, ERlow) in 12.5 % and was more than 10 % in 87.5 % of cases. HER2 status corresponded to 0, 1+ and 2+ in the absence of gene amplification – in 50.0 %, 35.9 % and 14.1 % of patients, respectively. The rate of TILs 20 % was in 71.4 %, 10.7 % and 17.9 % of cases. After NACT with the inclusion of anthracyclines and taxanes ± platinum combinations (in BRCA mutated status), the patients underwent radical surgery (mastectomy or breast-conserving surgery) with an assessment of the pathological response.Results. 15.6 % of patients had a complete pathomorphological response (pCR) to treatment, which corresponded to the RCB-0 class and the pathomorphological stage ypT0N0. Residual tumor load with incomplete response was very significant – class RCB-I was noted in only 7.8 %, and RCB-II and RCB-III – in 39.1 % and 37.5 %, respectively. An increase in the size of the residual tumor and the number of affected lymph nodes were associated with an increase in the RCB class. Predictors of pCR achievement in luminal HER2-negative cancer were: grade G3, rare histological forms of BC (medullary, metaplastic), rate of TILs ≥30 %, low ER expression, and HER2 0 status.Conclusion. Assessment of Ki-67, tumor grade, ER and HER2 rate, and TILs before starting NACT will help identify a group of high sensitivity to chemotherapy and optimize the treatment strategy in aggressive luminal HER2-negative BC.

HER2-positive breast cancer is a unique subtype of the disease, not only in terms of aggressive biology, but also in terms of treatment options. Over the past 15 years, the strategy for treating early HER2-positive breast cancer has undergone a real evolution – from the absence of anti-HER2 therapy to the sequential introduction of adjuvant, neoadjuvant and post neoadjuvant approaches. This review describes key studies of systemic therapy for HER2-positive breast cancer stage I–III, which made it possible to establish clear priorities in the sequence of surgical and systemic steps, identify high risk groups which need of escalation of treatment, and determine the optimal anti-HER2 therapy for each steps, as well as de-escalation of stage I treatment without losing its effectiveness. The news from the latest cancer conferences (SABCS, ESMO, ASCO) on the impact of various biological markers on the effectiveness of anti-HER2 agents is presented. A clear concept of modern treatment of early HER2-positive breast cancer has been formed, allowing individualized approaches, and achieving better results of the therapy this aggressive biological subtype.

Chronic lymphocytic leukemia/small lymphocytic lymphoma. Clinical recommendations

Mantle cell lymphoma. Clinical recommendations

The huge global burden of oncological diseases is growing and measures to counter this complex challenge are high on national health agendas. The Russian National Long-Term Oncology Strategy 2030 defines priorities, goals and directions in the fight against cancer. Italso contains action plans for more effective prevention, earlier and more specific diagnosis and more effective treatment options. Against this backdrop, experts now suggest to complement standard oncology treatment strategies by adding Patient Blood Management (PBM). For many clinical disciplines where a low blood count and considerable blood loss are commonly encountered, this bundle of care is the new standard. Based on clinical and scientific evidence, it aims to optimise medical and surgical patient outcomes by clinically managing and preserving a patients blood. The principles of this comprehensive concept can and must be transferred to oncology, thus offering value in improving cancer care and the efficacy of medical institutions. Accumulating evidence demonstrates that anaemia and iron deficiency, but also thrombocytopenia, blood loss and coagulopathy are independent risk factors for adverse patient outcomes including morbidity, mortality, reduced quality of life and prolonged average length of hospital stay in both surgical and medical patients. For the timely and effective detection and correction of these risk factors, an international network of multi-disciplinary clinicians and researchers has developed PBM. The rapidly growing body of evidence for PBM not only shows improved patient outcomes, but also reduced resource utilisation including the use of allogeneic blood components. The reduction of allogeneic blood transfusion further improves patient safety and outcomes, since transfusion is another independent risk factor for adverse outcomes. Supported by WHO endorsements and following the recommendations of an increasing number of state or national health authorities, PBM is about to become a new standard of care. However, even though the aforementioned risk factors are highly prevalent in oncology settings due to chemo-/radiotherapy and the pathology of the disease, the integration of PBM in standard oncology treatment pathways is lagging behind. Thus, and in support of the Russian National Long-Term Oncology Strategy 2030 to improve quality of oncological care, with the support of the National Association of Specialists in PBM (NASPBM), the PBM Oncology Working Group of the Russian Federation was created, consisting of national and international experts in oncology and PBM. On July 9, 2020, the Working Group met to discuss the rationale for PBM in oncology and to assess the need to implement PBM in Russian oncology care. As a result, the Group recommended to include PBM as an integral part of standard oncology treatment pathways, delineated the action required from facilitating stakeholders in the Russian Federation, determined a roadmap for implementation and developed a national resolution as a call to action on the matter. Presented herein, this resolution acknowledges the global and local impetus to reduce cancer mortality, and the rationale for PBM interventions to improve patient outcomes and alleviate the social and economic burden of cancer on the healthcare system.

Features of management of oncohematological patients in the context of the COVID-19 pandemic. Lecture

Monoclonal gammopathy of renal significance (MGRS) is a new nosology in modern nephrology and oncohematology. MGRS is defined as kidney injury due to nephrotoxic monoclonal immunoglobulin produced by the B-cell line clone which does not reach the hematological criteria for specific treatment initiation. Monoclonal proteins pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: 1) limited knowledge about the MGRS among hematologists and nephrologists; 2) lack of necessary diagnostic resources in most health-care facilities; 3) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. Consensus document comprises the opinion of experts leading nephrologists and hematologists of Russian Federation on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy, 1516 of March 2019, Pavlov First Saint Petersburg State Medical University. The present Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses.

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

Clinical recommendations.

The training module was developed by the staff of the department under the leadership of the head. Department of Academician of RAS, Professor I.V. Poddubnoy and Rector of FSBEI DPO RMANPO of the Ministry of Health of Russia, Corr. RAS, Professor D.A. Sychev.

Clinical recommendations.

The article summarizes the experience of academic and pedagogical leading of universities in Russia to train specialists of new formation in oncology, in accordance with the challenges of modern society and the needs of the modernized health. There are prospects and the possibility of the introduction of advanced educational technology in health professional education on the basis of the competence approach. The modern model of continuing professional development is implemented in the departments of oncology leading Russian universities.

The study included patients with noninvasive cancer and stage T1a-b-cN0M0 invasive breast cancer who were treated between 1985 to 2009 in Russia (at the N.N. Blokhin Russian Cancer Research Center and at the Clinic of the Russian Medical Academy of Postgraduate Training, 1036 patients), and in the Netherlands (LUMC, 560 patients, National Cancer Register, 22196 patients). The comparative analysis of surgery types between countries was carried out. The frequency of organ-preserving surgeries for early breast cancer in Russian and in the Netherlands was identical (53.7 % and 52.5 %). The percentage of organ-preserving surgeries over the past 20 years in Russia was not significantly changed, whereas the decrease in the rate of organ-preserving treatment from 56.2 % to 41.2 % was observed in the Netherlands.This is most likely due to an increase in the number of patients in postmenopause (>60 years) from 53.1 % to 63.8 %. The main type of organ-preserving treatment in Russia is radical resection of the breast. In the Netherlands, lumpectomy with sentinel lymph node biopsy or axillary lymphodissection is the most common form of breast-conserving surgery today.

Much attention has been recently given to the prognosis of extranodal non-Hodgkin’s lymphomas (NHL). All currently available prognostic scales fail to fully characterize the prognosis of primary NHL of the eye and its accessory apparatus.The purpose of this study was to identify prognostic factors for vision and life in patients with primary NHL of the organ of vision. Retrospective and prospective studies of the specific features of the disease in 94 patients with primary NHL of the organ of vision revealed some factors influencing its prognosis.

Non-Hodgkin's lymphomas are extremely rare among all tumors of female reproductive system. Diagnostic mistakes and inadequate therapeu- tic tactics in these diseases are results of usual absence of alertness of gynecologists. The aims are to analyze reasons of diagnostic mistakes in patients with non-Hodgkin's lymphomas of female reproductive system and to discover definitive clinical and morphological characteristics of female reproductive system lymphoid tumors. During the period between 1989 and 2006, 305 cases of primary extranodal non-Hodgkin's lym- phomas were detected; female reproductive system was affected in 7% of patients (totally 40 patients), which were included in investigated group. In the whole analyzed group of women (n=40, median age 43 yrs, range 17-84 yrs), patients with primary lesion of female reproductive system had median age of 40 yrs and with secondary involvement - 46 yrs. Most of patients were fertile (60%, n=24). Such tumors was localized in breast in 40% of cases (n=16), in ovaries - 20% (n=8), in uterine corpus - 12,5% (n=5), in uterine cervix - 15% (n=6), and in vagina - remaining 12,5% (n=5). Average time from diagnosis to beginning of the treatment was 7,5 months. As a result, the onset of specific therapy was delayed in 65% cases (n=26) and 50% (n=20) underwent unneeded surgery. Diagnostic mistakes lead to inadequate treatment. Extranodal non-Hodgkin’s lymphomas of female reproductive system, both primary and secondary, are rare pathology. Primary lesion is more typical for older women, sec- ondary is mainly affecting younger women (in reproductive period). Chemotherapy response and prognosis are better in primary cases.

The purpose of the study was to define the factors influencing the development of a recurrence depending on the volume of surgical intervention and to investigate the possibility of performing organ-saving surgery (OSS) for centric breast cancer.The study used the clinical findings of 200 patients treated at the Department of Radiosurgery, N.N. Blokhin Russian Cancer Research Center in 1996 to 2006. According to the volume of surgical intervention, the patients were divided into 2 groups: 1) 106 patients who had undergone radical mastectomy; 2) 94 patients who had undergone radical resection. According to our data, the disease progressed in 32 (16%) cases. There were 12 local recurrences: in 8 (7.5%) and 4 (4.2%) cases after radical mastectomy and radical resection, respec- tively. The findings suggest that OSS may be performed after carefully patient selection, with all contraindications being kept in mind.

The BCIRG 001 study has shown that a combination of Taxotere, doxorubicin, and cyclophosphomide (TAC regimen) is more effec- tive than the standard FAC (5-fluorouracil, doxorubicin, cyclophosphomide) regimen in adjuvant chemotherapy of operable breast cancer (BC) with mestastases to regional lymph nodes. With higher efficacy, TAC regimen was more toxic: the incidence of febrile neu- tropenia was 24.7%. According to the current EORTC and ASCO guidelines, the use of granulocyte colony-stimulating factors (G-CSF) for primary prophylaxis is indicated when the risk of febrile neutropenia is ≥20%. This study was designed to evaluate the safety of TAC regimen with G-CSF primary prophylaxis in adjuvant chemotherapy (CT) of BC .Patients with operable BC (T1—3N1M0) and Karnofsky performance status 80% received adjuvant TAC regimen after radical surgery: Taxotere 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphomide 500 mg/m2. G-CSFs were administered in the standard doses for 5—7 days starting from cycle 1 of CT, for primary prophylaxis of febrile neutropenia.One hundred and one patients have been treated since 2006. Mean age was 47.5 years (range 25—67 years). Almost half (48.5%) of the patients had Stage IIIa disease, Stages IIa and IIb had 18.8 and 27.7% of patients, respectively.The tumor was estrogen receptor-positive in 57.4% of the patients and progesterone receptor-positive in 62.4%. Overexpression of Her- 2/neu receptor was documented in 49.5% of cases. The mean number of cycles per patient was 5.8. Ninety-one (90.1%) patients have received a complete course of 6 TAC cycles. The duration of prophylactic use of lenograstim or filgrastim during one CT cycle was 5.9 and 5.6 days, respectively.Episodes of febrile neutropenia were observed at 19 (3.2%) CT cycles in 9 (8.9%) patients. Neutropenic infections were recorded at 4 (0.78%) cycles in 3 (3%) patients.Thus, the use of GCSF substantially reduces the incidence of TAC-associated febrile neutropenia and infectious complications and ensures a safe and complete course of effective adjuvant CT for the vast majority (90.1%) of patients. The data presented suggest that there is a need for primary prophylaxis with G-CSF in all BC patients receiving adjuvant TAC.

The paper gives the results of studying the genes of epidermal growth factor receptor (EGFR) and topoisomerase IIα (TOP IIα) in patients with triple-negative breast cancer (BC). It is suggested that the lack of EGFR gene amplification might serve as a factor of good prognosis. TOP IIα gene amplification usually occurs in the tumors responsive to chemotherapy including anthracycline drugs. The altered status of the above genes should be interpreted in the context of aneusomy of chromosomes 7 and 17, on which they are located. No association was found between the pattern of EGFR and TOP IIα gene abnormalities and the basaloid phenotype of BC.

In the present review has described the historical stages of systemic therapy of breast cancer with the use of taxanes, and has given a detailed description of drugs (paclitaxel and docetaxel). The role of docetaxel (Taxotere) in reducing the recurrences and death from cancer risk has shown. The major randomized trials has described; was studied the effectiveness of combination with docetaxel (Taxotere) in the adjuvant treatment of early breast cancer with or without lymph nodes involvement. The important role of docetaxel (Taxotere) in the adjuvant treatment of HER2-positive breast cancer was shown.

The results of treatment were studied in 95 patients with local recurrences of uterine sarcomas, who had been treated at the N.N. Blokhin Russian Cancer Research Center in 1972 to 2010. Two patient groups were comparatively analyzed after surgical and conservative (chemo- and radiotherapy) treatments. Overall survival was found to be significantly higher in the group of patients who had undergone surgical treatment.

Clinical, morphologic and immunohistochemical data of 51 patients with stage T2N1-3M0 breast cancer treated in the N.N. Blokhin Russian Cancer Research Center of Russian Academy of Medical Sciences in 2002 was analyzed. Expression of Pgp 170 was found in 19 patients. Relationship between immunophenotype of stage T2N1-3M0 breast cancer cells and main clinical and morphologic fea- tures, treatment provided and expression of multiple drug resistance gene MDR1.

Taking into account the fact that the treatment of advanced ovarian cancer includes cytoreductive surgery and chemotherapy, it is important to take advantage of contemporary highly effective agents. In 2003 the Regional program for optimization of ovarian cancer treatment in Cancer centers of Russia was initiated: 100 patients from 22 Cancer dispensaries received combination chemotherapy with Taxol at the dose of 175 mg/m2 as 3 hours intravenous infusion, then Carboplatin at the dose to obtain AUC=5,0 (TCb scheme). As a result of this multi-center study, the effectiveness of TCb scheme as first line chemotherapy was confirmed. The scheme can be successfully implemented in Cancer Centers.

The opening of the Russian program of quality control of immunohistochemical analyzes will increase the quality of diagnosis and treatment of malignant tumors, as well as optimize financial costs of oncology.

The review analyzed the role of capecitabine and eribulin in the treatment of HER2-negative metastatic breast cancer in patients pretreated with anthracyclines and taxanes. The mechanism of the antitumor action of capecitabine and eribulin, the efficacy in various biological subtypes of breast cancer and safety of treatment is described. The results of a comparative analysis of the efficacy and safety of eribulin monotherapy compared with capecitabine therapy as a second-line treatment for advanced HER2-negative breast cancer are presented.

For decades taxanes are used as a part of classical schemes for treatment of malignant tumors of various localizations including breast cancer. Peripheral neuropathy is an adverse reaction which impairs both quality of patients’ lives and treatment efficiency. To prevent or reduce the impact of peripheral neuropathy factors contributing to its development and mechanisms that are involved need to be known. This article is a review of the current status of our understanding about the mechanisms underlying the development of taxanes induced peripheral neuropathy.

The aim. To study the clinical and radiological evaluation of the effectiveness of preoperative systemic therapy and to compare the results of macroscopic and microscopic evaluation of response in different biological subtypes of breast cancer (BC). Materials and methods. The study included 213 women with breast cancer stages T1-3N0-1M0, treated by preoperative systemic therapy and radical surgery with morphological evaluation of the response in the N.N.Blokhin National Research Oncology Center from 2004 to 2017. All patients had clinical and radiological examination (mammography and ultrasound) before and after neoadjuvant systemic therapy. The rate of morphological response was assessed in different biological subtypes and the rate of pCR was compared with the clinical, radiologic and macroscopic morphological data, statistical analyses was made by SPSS 20.0, the differences were considered reliable at p

Abstract Relevance. Circulating tumor cells (CTC) are a biological marker of new generation, which provides additional information on the biological features and prognosis of the disease. The possibility of using CTC for early evaluation of the effectiveness of drug treatment of breast cancer (BC), including neoadjuvant chemotherapy, is an important but insufficiently studied issue. Goal - to study the dynamics of CTCs in the process of preoperative chemotherapy in patients with locally-advanced BC. Materials and methods. Between 2015 and 2016 59 women over the age of 18 with verified BC and signed informed consent were included in the study. Patients with stage II and III were included. CTCs were evaluated in the blood before the start of treatment, after 2 courses of chemotherapy and before surgical treatment. To detect CTCs we used the ISET (Isolation by Size of Tumor cells) technique, based on vacuum cell filtration through a membrane with a given pore size of 8 mcm. Results. In 22 (37%) women CTCs were detected before treatment, including 6 (10%) patients with CTCs found on every stage of treatment. Among 37 (63%) patients without baseline CTCs 19 (32%) developed them in the process of chemotherapy. Baseline CTCs correlated with tumor size more than 25 mm and stage III disease. Also a tendency to increased CTC prevalence in patients with poor pathological response to chemotherapy was revealed. Conclusions. CTCs represent a novel biomarker. Yet, methodology needs to be standardized and more structured studies are badly needed to reveal their true biological relevance.

Objective. To study the predictive factors of achievement pathological complete response (pCR) at neoadjuvant chemotherapy primary operable breast cancer. Materials and methods. Analyze of the rate of pCR after neoadjuvant systemic therapy in different clinical factors and biological characteristics was made for 164 patients (24-76 years; median - 47 years) treated in RCRC from 2004 to 2016. Results. Predictive factors for high rate of pCR after neoadjuvant systemic therapy in primary operable breast cancer were hormone negative status, HER2-overexpression, Ki-67≥20% and Grade 3 of tumors, p

Since 2006 the epidemiological HER2 screening program in patients with breast cancer was started in all federal regions of Russia. The main aims of this program were implementation HER2 diagnostic in routine practice and improvement diagnostic on regional level. The data received in frame of execution of this program is important additional information that used for analysis of annually published journal "State of Oncology Aid Rendered to Population of Russia". This article presents results of HER2 screening epidemiological program in 2015 and provides comparative data analysis since 2012 to 2016 years.

Breast cancer is the most common female oncopathology in the world. The main cause of mortality in patients - metastases. The current state of medicine allows curing the primary tumor, but often is not effective enough to control the development of metastatic disease. Of great importance in the implementation of metastatic cascade plays circulation and survival of tumor cells in the peripheral blood. In this article we have tried to summarize and present the data in the literature on the study of circulating tumor cells in patients with breast cancer.

In experimental models it was shown that the family of insulin-like growth factors (IGF), the main representative of which is IGF-1 exerts mitogenic, antiapoptotic and angiogenic activity. It is known that IGF-signaling pathway is involved in the activation cascade of the mitogen-activated protein kinases, resulting in the blocking of apoptosis. Clinical studies confirm the need for the involvement of IGF signaling pathway in the development and progression of ovarian cancer (OC).Subjects and methods. The study included 44 patients with ovarian cancer, 7 patients with borderline and 14 benign ovarian tumors. The ELISA analysis determined the content of insulin-like growth factors type 1 and 2 in tumor tissue and serum of patients with neoplasm of the ovary.Results. In the tissue of ovarian cancer content of IGF-1 were significantly lower than in the tissue of benign tumors. Serum levels of IGF-1 and IGF-2 correlated negatively with the prevalence of OC. Found direct correlation between levels of IGF-1 and IGF-2 in ovarian cancer tissue, and poor direct correlation between serum levels of IGF-1 and IGF-2. The median follow-up period was 14 months and the median time without recurrence was 13.5 months. It is established that two-year disease-free survival is reduced by 40% when low serum levels of IGF-I, and 30% at low levels of IGF-2. In patients with residual tumor size less than 1 cm with high serum levels of IGF-1 (87 ng/ml) two - year disease-free survival was 66.2%, and at low levels of IGF-1 - 25% (p=0.016).Conclusions. The levels of IGF-1 and IGF-2 in tumor tissue and serum in patients with ovarian cancer were decreased in the tumor process. Elevated levels of IGF-I can be considered as a factor of favorable prognosis in patients with ovarian cancer who underwent cytoreductive surgery with residual tumor of less than 1 cm.

Preoperative systemic therapy of breast cancer is one of the most promising and rapidly developing areas of modern oncology. Effective preoperative systemic treatment modifies the subsequent surgical step, contributes to the elimination of subclinical micrometastases and carcinoma sensitivity assessment for this type of therapy. However, the main goal is to achieve complete morphological regression, as a predictor of favorable prognosis of the disease. The proportion of patients who achieved a complete tumor response to preoperative effective systemic therapy is steadily growing, which creates certain difficulties at all steps of surgical treatment due to loss of macroscopic tumor area. Placement of image-detectable marker into the primary tumor and assessment of the status of regional lymph nodes before the start of systemic therapy, preoperative demarcate the residual tumor, planning volume of removed tissue, evaluation of resection margins and clipping the tumor bed for adjuvant radiation therapy with boost is a continuous chain of modern multidisciplinary approach in the treatment of breast cancer, the need to implement in clinical practice becomes apparent.

Since 2006 the epidemiological HER2 screening program in patients with breast cancer was started in all federal regions of Russia. The main aims of this program were implementation HER2 diagnostic in routine practice and improvement diagnostic on regional level. The data received in frame of execution of this program is important additional information that used for analysis of annually published journal "State of Oncology Aid Rendered to Population of Russia". This article presents results of HER2 screening epidemiological program in 2014 and provides comparative data analysis since 2012 to 2014 years.

Matrix metalloproteinase-7 (MMP-7) is able to cleave almost all the elements of the extracellular matrix. It is believed that due to its ability to degrade the basal membrane, it is involved in the processes of invasion, metastasis and neoangiogenesis. Vascular endothelium growth factor (VEGF) has demonstrated its role in tumor progression. Subjects and methods. The study included 65 patients with tumors of the ovary, 44 cancer was diagnosed. Using enzyme-linked immunosorbent assay we determined the content of MMP-7 and VEGF in the serum and tumor tissue in patients with tumors of the ovary. Results. Serum levels of MMP-7 and VEGF are positively correlated with the prevalence of ovarian cancer (OC). In the tissue of adenocarcinoma of the ovary are determined higher levels of MMP-7 and VEGF than in tissue of benign tumors. In the tumor tissue of OC registered positive correlation between VEGF and MMP-7 (r=0.6); p=0.0001. The period of observation did not exceed 2 years from the start of treatment, median follow-up time was 14 months. Only the size of residual tumor after cytoreductive surgery is significantly associated with long-term results. Communication levels of MMP-7 with long-term results of treatment of OC patients is not established. Two-year disease-free survival in patients with baseline serum VEGF value of more than 440 PG/ml was 24%, less than 440 PG/ml - 55%. Conclusions. The levels of MMP-7 and VEGF in tumor tissue and serum in patients with OC increase with the prevalence and aggressiveness of tumor process. Elevated levels of VEGF can be considered as a factor of poor prognosis in patients with OC.

The system of the insulin-like growth factors (IGF) through its mitogenic and antiapoptotic effects plays an important role in carcinogenesis. IGF with interaction with own receptor activates Ras - and Akt-signaling pathways that lead to enhanced cell proliferation and reduction of apoptosis. Via stimulation of proangiogenic factors, such as vascular endothelial growth factor (VEGF), IGF also mediates processes of neoangiogenesis that are necessary for the development, progression and metastasis of malignant tumors. Recent data show a linkage between IGF, VEGF and ovarian cancer. New drugs of targeted therapy for patients with ovarian adenocarcinoma, that inhibit the components of IGF and VEGF families, are under experimental and clinical trials. This review presents the results of investigations of IGF′ and VEGF′ role in the development, prognosis and treatment of patients with ovarian cancer.

We shows the Russian Breast Cancer (BC) Register-based analysis, established under the auspices of the non-profit making partnership "Equal right to life" with the inclusion of 49784 BC patients under the examination and treatment in 18 cancer institutions of the Russian Federation between 1985 and 2014 years. Stage distribution in patients with BC, included in the Patient Register, is absolutely identical to the official statistics of malignant neoplasms in Russia (edited by A.D.Kaprin, 2014); it is the real situation in our country. BC early detection is not good enough in all regions of the RF: the proportion of non-invasive cancer (in situ) is less than 1% and stage I BC - 18,3% (15-26%). We have identified the important features of the population-based "portrait" of BC: women with advanced stages of BC (III andIV) are usually of old age in our country, but not the young one. It appears that, women older than 60 years do not participate in BC screening program and will visit the oncologist only when significant clinical symptoms of the disease are appeared. Stage I breast cancer has positive "biological" portrait: a high proportion of luminal HER2 negative subtype of cancer and the extremely low proportion of HER2+ subtypes; there are only 11,8% of patients suffering from stage I HER2+ breast cancer. Patients with locally advanced (stage III) and metastatic cancer (stage IV) have more aggressive forms of tumors; more than 40% of cancers are HER2+ and triple negative immunophenotype of BC. The modernization of BC early detection programs in the RF will not only help to improve the disease prognosis, but also to save spending on expensive medicines (cytostatic and targeted therapy) which are used for treatment in such cases.

This review deals with the detail presentation of the antitumor immunity basic mechanisms, of the interpretation of HLA class I and II histocompatibility genes - markers of the antigen-activated lymphocytes in the antigenic activation of lymphocytes and the role of T-cells (CD8+ T-killer cells and CD4+ T-helper cells) and NK cells in the realization of antitumor responses. We have described the unique mechanisms of cooperative humoral and cellular antitumor immunity - antibody-dependent cell-mediated cytotoxicity, and have evaluated its role in antitumor protecting the body against cancer. Advantages of the antitumor immunity is the possibility of T-lymphocytes to recognize tumor antigens in histocompatibility molecules of HLA-class I and II and-NK-cells to kill tumor cells without expression of HLA-class I and to acting in antibody-dependent cell-mediated cytotoxicity. The mutated cells can avoid the immune surveillance and cells cloning, the basis of these mechanisms is important immune processes; tumor progression can occur as a result of immune system damage (imperfect antitumor immunity) or as a result of tumor "immune invisibility". The causes of imperfect antitumor immunity are: the loss of tumor presentation histocompatibility molecules of HLA-class I and II, leading to the inability to show T-cell cytotoxicity, the expression of HLA-E and HLA-G, leading to blockade of NK-cells activity, the presence of suppressor Foxp3 + regulatory lymphocytes in tumor, the development of immunological tolerance (sustainable "unresponsiveness" of the immune system) during tumor growth and dissemination. We have showed the perspective study directions of prognostic and predicting roles of the immune tumor characteristics: subpopulations of stromal and intratumoral TILs, the markers expression HLA class I and II histocompatibility genes and non-classical suppressor molecu- les of HLA-E and HLA-G and tumor-infiltrating Foxp3(+)-lymphocytes. The study of the cellular and molecular basis of immune mechanisms will help us better understand the carcinogenesis and will optimize the therapeutic strategy for BC.

Aim is to examine the biological, population-based and prognostic value of immunological heterogeneity of stage I breast cancer (BC) in two independent populations (Russian and Dutch).materials and methods: we studied the clinical, morphological characteristics and disease course in 518 patients with stage I BC, who received treatment in N.N.Blokhin Russian Cancer Research Center, in the Hospital of Russian Medical Academy for Postgraduate Education of the Ministry of Health of the Russian Federation (n=315) and in Leiden University Medical Center - LUMC (n=203) between 1985 and 2010 years. Tumor tissue paraffin blocks had been examined at the LUMC; morphological characteristics were included the de-gree of anaplasia, histological type (solid tumor slide) and tumor markers (ER, PR, HER2, Ki67, HC10, HCA2, HLA-E, HLA-G, Foxp3), whose expression was validated by immunohistochemistry on tumor tissue microarrays. The expression of immune markers, the immunological heterogeneity of stage I BC were studied in Russian and Dutch women, and we also indicated 3 types of tumor immunogenicity (high, moderate, low). We studied population and prognostic role of immunogenicity as a further prediction in patients with stage I BC (in the general group, subgroups of patients treating with/without adjuvant systemic therapy). Statistical analysis was performed using international statistical program SPSS 20.0; differences were considered statistically significant when p

Aim: to study the prognostic value of clinical and morphological factors for the risk of recurrences in breast cancer stage I.Materials and methods: In study included 1341 women with breast cancer stage I (T1a-b-cN0M0), treated in the RCRC and RMAPE 1985-2012. We analyzed the clinical factors (age, volume of surgery, radiotherapy, type of adjuvant systemic therapy) and morphological factors (status of estrogen and progesterone receptors, HER2-status, proliferation activity index Ki-67, biological subtype, presence of lymph vascular invasion and intraductal component and the tumor size T1a-b-c). We assessed the risk of recurrence (median follow up - 96 months), the rate of relapse and disease-free survival in different subgroups using univariate and multivariate COX-regression analysis. Results: In univariate COX-regression analysis we found the prognostic value for the risk of recurrences of such morphological factors: grade of tumor ( p =0,034), histological type ( p =0,025), tumor size T1a-b-c ( p =0,004), presence of lymph vascular invasion ( p =0,03) and biological subtype of breast cancer ( p =0,002). The most favorable is the luminal A subtype with minimal rate of distant relapses (1,6%), the maximum time to progression (median - 48 months) and the best rate of the 5- and 10-year disease-free survival (97,2 and 93,8% respectively). The most important clinical factors were age ( p =0,001), the volume of surgery ( p =0,032), the using of «boost» after breast conservingtherapy ( p =0,007), and presence of adjuvant systemic therapy (chemotherapy, endocrine therapy or both therapy in accordance with the biological subtype, p

This review includes the main steps of anti-HER2-therapy for breast cancer (BC). Up to 30% of breast tumors overexpress epidermal growth factor receptor HER2/neu, and this expression is correlated with poor prognosis and course of the disease. Determination of HER2-status in BC is mandatory for all stages, it is necessary to evaluate the prognosis and development of optimal therapeutic algorithm. The first targeted therapy developed in 1992 for the treatment of HER2-positive BC, has become trastuzumab (Herceptin). The unique mechanism of Herceptin (targeted blockade of HER-dependent signaling pathway, the blockade of the activation of PI3K and MAPK signaling pathway, activation of antibody-dependent cellular cytotoxicity, etc.) and high efficiency have significantly changed the prognosis of HER2-positive BC. The important role of 1-year adjuvant therapy with Herceptin has showed in large international trials (HERA, NSABP B-31, NCCTG 9831, BCIRG 006) for reducing the risk of recurrence (50%) and death (30%) in HER2-positive BC. Neoadjuvant chemotherapy with trastuzumab has studied in the large randomized trials (NOAH, GeparQuattro, GeparQuinto), which has been shown to benefit of Herceptin in the rate of pathological complete response and significant improvement of survival. The effectiveness of Herceptin in metastatic HER2-positive BC has showed in the large studies (M7701, HO648g, BCIRG 007, HERNATA, etc.) The advent of pertuzumab opened new perspectives for the treatment BC: pertuzumab inhibits HER2-receptor dimerization with other HER- receptors (HER1-3) and blocks the HER-mediated signaling pathways, activates of antibody-dependent cellular cytotoxicity. The combination of pertuzumab and trastuzumab blockade provides more HER2-mediated intracellular signaling pathways than either drug alone, which leads to a more pronounced anticancer response. In a large randomized study CLEOPATRA had shown unprecedented results of treatment of metastatic or recurrent BC: the increasing median of overall survival up to 56,5 months, regardless of age, race, the prior treatment, hormone receptor status and location of metastases. The benefit of pertuzumab has shown in old patients, patients with brain metastases, as well as a significant increase in progression-free survival. The new class of anti-HER2-agent - conjugates, appeared last time. Trastuzumab emtanzin (T-DM1) - the first conjugate the targeted monoclonal antibody trastuzumab, cytotoxic chemotherapy agent (DM1) and linker. Antitumor effect of T-DM1 sum of the effects of trastuzumab (targeted blockade of HER-dependent signaling pathway) and targeted delivery of high effective agent (DM1), which causes cell death by disrupting microtubule polymerization and cell cycle arrest. Efficiency T-DM1 has shown to increase disease-free survival, rate and duration of response and overall survival in patients with HER2-positive advanced BC pretreated with taxanes and Herceptin (EMILIA trial). Modern treatment options in HER2-positive BC perfectly combine high efficiency, safety and saved the quality of life.

HER2 overexpression in breast cancer is an extremely unfavorable prognostic factor determining extensive tumor growth, early distant metastases, and resistance to treatment. To predict the disease course, one of the most important diagnostics steps - HER2 testing - is performed in settings of specialized laboratories at medical institutions. This article summarizes the results of Epidemiological HER2 screening program in patients with breast cancer in 2013 in Russian regions: results of HER2 testing have been analyzed and the changes in the identified parameters have been tracked compared with 2012 data.

The article reports the preliminary results of the observation program studying the application of bevacizumab in patients with metastatic colorectal cancer (mCRC) in daily clinical practice in Russian.Methods. The observation program is based on the results of treatment of 250 patients with metastatic colorectal cancer. The observation program included patients receiving bevacizumab from the first-line of chemotherapy. We were analyzing main demographic factors of the group of patients, survey plan before the treatment, the choice of chemotherapy regimens, dosage and reason for cessation of bevacizumab, frequency of drug usage as a supportive care.Results. The program enrolled 250 patients, where 89 (36%) patients were suffering from rectal cancer, 159 (64%) - from colonic cancer and 2 (1%) from multiple primary rectal colonic cancer. At baseline, 137 (35%) patients had synchronous distant metastases. Only in 32 (13%) patients who were enrolled in the program the primary tumor was not removed. The first-line bevacizumab-based supportive therapy was received by 120 (48%) patients. More than one line of chemotherapy was received by 47 (18,8%) patients. The median duration of bevacizumab-based treatment was 6 months. Bevacizumab therapy was discontinued in 115 (46%) patients; the main reasons for the discontinuation of bevacizumab were progression (49 patients, 43%), lack of drugs (29 patients, 25%), refusal of treatment (15 patients, 13%). During the program 48 (19%) patients developed side effects, 21 (43%) patients among them had grade 3 and 4 side effects. The analysis of treatment effects was estimated in 239 patients: 84 (35,1%) patients showed clinical (complete and partial) response. Conclusion. The targeted therapy in clinical facilities of the Russian Federation cannot be used because of scarcity supply and the oncology specialists willingness to realize the optimal therapeutic approaches. For one part, the results show that involving bevacizumab have failed to increase the toxicity of chemotherapy, for the other part the combination of bevacizumab with standard chemotherapy regimens can help to achieve high disease control rates.