Vol 17, No 1 (2015)


The improvement in overall survival for patients with metastatic breast cancer treated with eribulin: the resolution based on results of the expert council

Andrianova V.S., Beliaeva A.V., Bolotina L.V., Vazhenina A.A., Varlamova S.E., Vladimirov V.I., Vladimirova L.Y., Voznyi E.K., Demidov S.M., Zhukov N.V., Zhukova L.G., Imianitov E.N., Kovalenko E.I., Kogoniia L.M., Konstantinova M.M., Lan S.A., Lichinitser M.R., Manziuk L.V., Manikhas A.G., Mukhametshina G.Z., Semiglazov V.F., Semiglazova T.I., Seregina G.V., Stroiakovskii D.L., Ter-Ovanesov M.D., Chichkanova A.S.
Journal of Modern Oncology. 2015;17(1):5-8
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Breast cancer immunology: theory and prospects (review)

Kolyadina I.V., Poddubnaya I.V.


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.
Journal of Modern Oncology. 2015;17(1):12-18
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Quality of life is the fundamental criterion of the efficacy of targeted therapy in patients with metastatic Her2-positive breast cancer

Semiglazova T.Y., Dashyan G.A., Semiglazov V.V., Zhabina A.S., Osipov M.A., Kotova Z.S., Klimenko V.V., Krivorotko P.V., Semiglazov V.F.


Since the 1990s, the unique data of clinical trials has been analyzed regarding the Quality of Life (QoL) Index as a one of fundamental criteria of treatment efficacy for malignant tumors and breast cancer in particular. Last decades the highest progress was shown in the treatment of HER2-positive subtype of BC. New biological therapy with anti-HER2 targeted agents (pertuzumab and T-DM1) significantly improve overall survival in HER2-positive BC, increase disease-control rate and associated with good quality of life. QoL measurement by special Questionnaires is a simple and accurate option to evaluate the patient's reaction to disease and its treatment in detail.
Journal of Modern Oncology. 2015;17(1):19-24
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A population-based portrait of breast cancer in russia: a cancer register-based analysis in russian

Poddubnaya I.V., Kolyadina I.V., Kalashnikov N.D., Borisov D.A., Makarova M.V.


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.
Journal of Modern Oncology. 2015;17(1):25-29
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Immunological heterogeneity of stage I breast cancer:biological, population-based and prognostic value (international cooperation experience)

Kolyadina I.V., Poddubnaya I.V., Van de Velde C.J., Kuppen P.J., Frank G.A., Komov D.V., Karseladze A.I., Bastiaannet E., Dekker-Ensink N.G.


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 <0,05.results: tumor immune characteristics in patients with stage I BC have important population-based differences: BC highly express molecules of HLA class I (HC10+ in 91%, HCA2+ in 48%, combined expression of the HC10+ nsa2+ in 48% of cases), and also highly express non-classical markers HLA class I (HLA-E+ in 99%, HLA-G+ in 26%) in russian women. The Russian women breast cancer is highly tumor-infiltrating Foxp3(+) regulatory T-cell (in 73% of cases), associated with the suppression of antitumor response. As a result, Russian women breast cancer is highly immunological only in 14% of the cases. Breast cancer in women in the Netherlands moderately presents the molecules of HLA class I (HC10+ in 74% of cases, HCA2+ in 41%, the combined expression of the HC10+HCA2+ in 38% of cases), moderately expresses non-classical markers (HLA-E+ in 48%, HLA-G+ in 47%) and the tumor-infiltrating Foxp3(+) regulatory T-cell is observed only in 43%; the high immunogenicity of the tumor is indicated in 31% of cases, which can explain the high survival rate in Dutch women suffering from stage I BC without using adjuvant systemic therapy. Immunogenicity of the tumor is the important prognostic factor for both populations; we have noted the higher risk of recurrence, disease progression and death in patients with low tumor immunogenicity in general group and subgroup of women with BC without using adjuvant systemic therapy. The use of adjuvant systemic therapy can help to neutralize the negative impact of low tumor immunogenicity and to significantly improve the prognosis in case of stage I BC.
Journal of Modern Oncology. 2015;17(1):30-38
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Radiation-induced lung injury in breast cancer patients after breast conservation therapy

Trofimova O.P., Tkachev S.I., Ivanov S.M., Utkina V.L., Cheban O.I., Glebovskaya V.V.


Aim: the problem of postradiation lung injury is extremely topical, because of the close proximity to vital organs and the need of the significant part of tissue to receive the high dose of radiation in patients with breast cancer (BC). The aim of the analysis is to determine the frequency, severity of radiation damage to the lung tissue in women with BC, the frequency dependence on the technology of radiation therapy (RT) and the dose of radiation exposure, using 2D-conventional and 3D-conformal radiation therapy.materials and methods: we analyzed the data concerning the studies of thoracic organs (X-ray and computer tomography investigation) in 513 Tis-2N0-2M0 BC patients, receiving complex organ sparing treatment between 1996 and 2013 years. 318 patients were treated with postoperative 2D-conventional radiotherapy to a dose of 50 Gy, 195 patients - with 3D-conformal radiotherapy.results: we indicated that radiologically detected lung injury occur equally often in case of using 2D and 3D radiation therapy: 27,4 and 28,7%, respectively ( p >0,05); their frequency was significantly increased by 20-24% during radiotherapy only of the mammary gland and 37-41% - when doctors added the radiotherapy of cervical, supra - and infraclavicular regions. We showed that the risk of radiation pneumonitis in the ipsilateral lung was more than 25% and was significantly increased on the V20 increasing of the average dose to the lung more than 15 Gy.
Journal of Modern Oncology. 2015;17(1):39-43
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The use of combined plastic interventions in the reconstruction of post-operative soft tissue defects of the chest wall in the surgical treatment of locally advanced breast cancer

Vashenko L.N., Daschkova I.R., Bakulina S.M., Andreyko E.A.


The use of combined plastics extensive wound defect integumentary tissues of the anterior chest wall, which emerged after radical mastectomy with locally advanced cancer of the breast, have enabled us to achieve a good aesthetic and functional results without compromising the radical surgical treatment of cancer patients.
Journal of Modern Oncology. 2015;17(1):44-48
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The role of targeted therapy in the treatment of advanced hepatocellular carcinoma

Shakhnovich E.B., Kerbikov O.B., Kulaga E.A.


Hepatocellular carcinoma (HCC) is the most common cancer in the world. The success of HCC therapy directly depends on diagnosis of early stage of the disease and proper treatment in a timely manner. According to the current recommendations, the systemic standard chemotherapy is not the best option for treating patients with advanced HCC. Nexavar (sorafenib) is currently the only approved targeted drug for the HCC treatment. Sorafenib is the first targeted drug with proven ability to improve overall survival in patients with HCC, compared with placebo. Researchers have already gained extensive experience in treatment HCC using sorafenib within the context of international clinical trials (SHARP, Asia-Pacific, GIDEON), and in actual clinical practice in Russia.
Journal of Modern Oncology. 2015;17(1):50-54
pages 50-54 views

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