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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.

Bendamustine is a uniquely structuredalkylating agent that lacks cross-resistance with other alkylators. This agent has a high degreeof activity against a variety of tumor cell lines.Based on clinical data from randomized phase III trials, bendamustine, with or without rituximab, hasbeen shown to be an appropriate option for first-line treatment or treatment of relapsed/refractory patients with indolent non-Hodgkin’s lymphoma or elderly patients with mantle cell lymphoma. Bendamustine treatment is associated with abetter therapeutic index and offers an improved overall quality of life compared to R-CHOP or R-CVP. It is now often used as achemotherapy backbone for combination with novel drugs including ibrutinib or idelalisib. This article provides a comprehensivesummaryof the clinical data along with practical adviceonhowto optimallymanagepatients with bendamustine therapy, includingdose recommendations, antiemetic prophylaxis, prevention of infusion and skin reactions, as well as prophylaxis of opportunisticinfections. This information might be helpful for clinicians using bendamustine in their daily practice.

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.

Tamoxifen is a selective modulator of estrogen receptors and is widely used in receptor-a-positive breast cancer treatment. Adjuvant tamoxifen treatment substantially reduces breast cancer relapse and mortality rates. However, high interindividual variability in response is observed. One of the causes of this variability may be genetic polymorphisms of the cytochrome P450 (CYP) enzymes, which are responsible for the formation of tamoxifen active metabolites. Polymorphisms of genes encoding the enzymes with decreased or absent activity could be associated with lower tamoxifen active metabolites concentration in serum and consequently reduce the effectiveness of treatment. Pharmacogenetic approach is a promising tool of personalized medicine and may help personolize pharmacotherapy of breast cancer in the future. Throughout this review we analyze the up-to-date information on the influence of the gene CYP2C19 polymorphisms that they have on pharmacokinetic and pharmacodynamic of tamoxifen.

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.

The main method of treatment of patients with metastatic GIST is targeted therapy using tyrosine kinase inhibitors in contrast to localized forms of the disease. The efficiency and the duration of targeted therapy efficiency are the main prognostic factors in patients with metastatic gastrointestinal stromal tumors (GIST). Targeted therapy was ineffective among patients with the median survival of only 12-19 months, whereas in cases of effective targeted therapy the median survival was incomparably higher - 60-72 months. The main prognostic factors in patients with primary localized gastrointestinal stromal tumors are: the size of the primary tumor, mitotic index, the localization of tumors, mutation status and morphological characteristics of GIST. Taking into consideration that the main method of treatment in patients with disseminated GIST is drug therapy, the predictive values of several mentioned factors have lost the value, but other factors such as mutation status, morphological characteristics, the number and size of tumors and the localization of metastatic nodes have become more important.

Primary presentation of intradural non-Hodgkin lymphoma (PDL) is rare. Most published cases of PDL are single-patient reports. This lesion occurs more often in middle-aged women, in contrast to brain parenchyma primary central nervous system lymphoma (PCNSL), which has a slight male predilection. In contrast with parenchymal PCNSL, there has been no clear association between acquired and congenital immunosuppression and the development of PDL. The pathogenesis of PDL is not well understood because the dura is devoid of any lymphoid tissue. One hypothesis is that a benign inflammatory condition of the dura could attract polyclonal lymphocytes from which a monoclonal lymphoma could arise. B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) have been recognized as an important pathologic subtype. A PDL is more indolent and has a better prognosis than parenchymal PCNSL or systemic lymphoma with CNS metastasis. However, further studies with longer clinical follow up are necessary to assess the final outcome in these patients. In general, patients with marginal zone lymphoma have a favorable outcome, with a 5-year overall survival rate greater than 86%, without significant differences between gastrointestinal and nongastrointestinal and between localized and disseminated disease.

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.

Given the high rate of recurrence of epithelial ovarian cancer after radical treatment is necessary to improve the therapeutic approach to its treatment. New drug of marine origin trabectedin has shown high efficacy in monotherapy and in combination with different cytostatics in the treatment of platinum-sensitive recurrent of ovarian cancer. A randomized trial OVA-301 showed the greatest benefit of a combination of trabectedin with pegylated liposomal doxorubicin in the subgroup of patients with partially platinum-sensitive recurrent of ovarian cancer. Acceptable toxicity profile of the drug, presented mainly neutropenia and transient increase of transaminases, making it promising for further study.

Literature review on the results of clinical studies of the condition of bone mineral density (BMD) in patients with breast cancer (BC) is represented. Evidence of significant change in BMD in patients with breast cancer after adjuvant chemotherapy and hormonal treatment are given. Meaning of menopausal status, hormone therapy options on the state of BMD in patients with breast cancer were reflected. Effectiveness of bisphosphonates for the prevention of reduction of BMD in patients with breast cancer was shown. Data on more effective immediate bisphosphonates against delayed administration were presented. Current algorithms bisphosphonates in patients with breast cancer to prevent decline BMD were reflected.

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.

Antitumor activity of trabectedin as a monotherapy in different solid tumors (soft tissue sarcoma, ovarian cancer, breast cancer, melanoma) contributed to research trabectedin-based drug combinations. Phase I trials were searching for optimal dose and schedule of administration trabectedin and trabectedin-based combinations. This review considers aspects of clinical applications and toxic profile of trabectedin alone and combinations, including a rare adverse event – rhabdomyolysis and data of own experience.

The prognostic value of p53 nuclear expression in Stage 1 (T1N0M0) breast cancer was studied in 315 women treated in Russia (at the N.N.Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, and at the Clinic of the Russian Medical Academy of Postgraduate Education) in 1985 to 2009. An immunohistochemical assay for determining the expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 and the nuclear expression of p53 receptors was carried out at the Leiden University Medical Center. p53 nuclear expression was found in 14,7% of cases and statistically significantly correlated (p0,05) of p53 expression for the risk of further progression and death. It was suggested that the negative impact of p53 expression in the entire group might be compensated for by the positive role of adjuvant systemic therapy. Subgroup analysis showed that the patients with p53-positive tumors who did not receive any adjuvant drug treatment had the worst relapse-free and cancer-specific survival rates (p

Objective: to estimate the average duration of therapy with Avastin (bevacizumab) in patients with metastatic colorectal cancer (mCRC) in the daily clinical practice of cancer care facilities in Russia. Methods. The observational program is being implemented on the initiative of the Russian Medical Academy for Postgraduate education RF (Moscow) and it is based on the results of treating patients with mCRC in 24 clinical centers from different regions of the Russian Federation. The observational program includes patients receiving drug treatment for mCRC in accordance with the local standards and guidelines. Program patient enrolment has not been over yet. The paper presents preliminary results. Results. As of March 1, 2013, the program enrolled 117 patients, including 43 with rectal cancer and 74 with colon cancer. At baseline 70 (60%) patients had synchronous distant metastases and 47 (40%) patients developed synchronous distant metastases after primary radical surgery. At the analysis, 112 patients were treated with bevacizumab in combination with different chemotherapy (CT) regimens; 25 patients received more than the 1 line of CT, in 8 of them bevacizumab was discontinued (because of disease progression in 6 cases); 33 (29%) patients were switched to bevacizumab monotherapy during treatment. The effect of CT with simultaneous administration of 7–10 infusions of bevacizumab was preserved in 73% of the patients; 4 and 27% showed complete and partial responses, respectively; stabilization was noted in 42%. Sixty-three (56%) patients received symptomatic therapy. Adverse events were observed in 18 (16%) patients, 13 of them had grade 4 reactions. Conclusion. Targeted therapy with bevacizumab is in considerable use in the health care facilities of the Russian Federation. The addition of bevacizumab to CT does not increase toxicity of CT. The combination of bevacizumab and standard CT regimens can achieve high disease control rates.

Tumors of unknown primary site (CUP-syndrome) – an intriguing clinical phenomenon that each year 5% of patients with newly diagnosed malignancies. The absence of clinical manifestations of the primary tumor, early development, unusual, often multiple metastases – signs of this heterogeneous group of neoplasms. However, there is no consensus whether the CUP-syndrome metastases undetected primary tumor or an independent biological phenomenon with certain genetic and phenotypic characteristics. Identification of major molecular abnormalities that characterize CUP-syndrome, slow progressive. Profile of gene expression and the expression of miRNAs are highly specific tests that can help to identify histogenesis of tumors without primary site.

We report a 33-year-old female patient with primary isolated malignant vulvar Langerhans cell histiocytosis (LCH). The effectiveness of hemivulvectomy with adjuvant EBRT and chemotherapy is presented. Adequate tissue excision followed by histological study with immunohistochemistry was of critical importance for the diagnosis in our case. Unified management recommendations with multidisciplinary approach are required.