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According to the results of the conducted studies in the early 2000’s, adjuvant trastuzumab for 1 year has been admitted the gold standard since 2006. However, the high cost of treatment and the increasing of the risk of cardiotoxicity have led to new clinical trials concerning the short-course trastuzumab regimen. The study deals with the results of the number of the largest randomized trials associated with the comparison of 6 months (the PHARE trial and the HORG study), 9 weeks (the Short-HER study and the SOLD study) and 12 months duration of adjuvant trastuzumab therapy in combination with chemotherapy in patients with HER2-possitive early breast cancer. Today, none of the studies has shown statistically significant evidence of the possibility to reduce the duration of adjuvant trastuzumab therapy.

Breast cancer is a leading oncologic disease among women worldwide. Though the achieved results in treating patients with luminal subtypes are high, there is a great demand on new approaches in this field. This article highlights the new CDK4/6 inhibitor ribociclib as well as presents clinical cases from the own clinical practice obtained during phase IIIb COMPLEEMENT trial.

Background. Gastric cancer is the fifth most common malignancy worldwide with diagnosis often occurring at an advanced stage. For the majority of advanced gastric cancer patients, chemotherapy typically is used as first-line treatment, although many patients will also require second-line treatment. Ramucirumab (Cyramza®, Eli Lilly and Company, Indianapolis, Indiana, USA) recently has received worldwide and United States Food and Drug Administration approval for gastric cancer in the second-line setting. Case reports. A series of five advanced gastric cancer cases is presented, outlining each patient’s diagnosis and treatment. All patients were treated with intravenous ramucirumab (8 mg/kg on days 1 and 15) plus paclitaxel (80 or 100 mg/m2 on days 1, 8, and 15 of a 28-day cycle) after disease progression on or after first-line chemotherapy. Patient outcomes are described including an outline of treatment-related adverse events and quality of life. All patients were able to achieve a clinical response and stable disease. Conclusion. Our case series demonstrates that ramucirumab, in conjunction with paclitaxel, is an effective and well-tolerated treatment option for advanced gastric cancer patients who have disease progression following first-line chemotherapy.

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

Dermatomyositis and polymyositis are an autoimmune disease which is characterized by proximal skeletal muscle weakness, muscle inflammation and associated with a variety of skin manifestations. Both autoimmune conditions are mainly observed as an independent disease, though an association between dermato- and polymyositis and malignancy were described. Case reports of two patients are presented, in one of which dermatomyositis and breast cancer were manifested simultaneously, in the other - the development of polymyositis preceded the recurrence of the disease after a long-term remission. Also diagnostic and therapeutic options of both conditions are shown.

Soft tissue metastases of the gluteal region in solid tumors observed very rarely. We described a unique clinical case of gluteal soft tissue metastases in HER2+ breast cancer; through close collaboration were able to confirm the progression of the breast cancer and plan the treatment strategy based on clinical data and biological subtype of breast cancer.

Background. Breast cancer is the most common cancer among women. Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, in which there are no special targets for therapy. Therefore chemotherapy is still leading treatment for TNBC including the regiments with platinum drugs.Aim. To study the association of polymorphic markers of the genes XRCC1 (rs25487), ERCC5 (rs17655), TP53 (rs1042522), CDKN1A1 (rs1801270) with progression-free survival (PFS) and overall survival (OS) of TNBC patients after platinum-based neoadjuvant chemotherapy.Materials and methods. Polymorphic markers of the XRCC1, ERCC5, CDKN1A and TP53 genes were studied in blood samples of 67 patients with stage II–III TNBC by real-time polymerase chain reaction with fluorescent allele-specific probes. The results of determining the markers were compared with PFS and OS using the Kaplan–Meyer method and the log-rank-test.Results. The association was found for the polymorphic marker rs25487 of the XRCC1 gene with PFS (carrying the T/T genotype was associated with a decrease of median PFS: 15.6 months versus 34.3 months, p = 0.013) and OS (carrying the T allele was associated with a decrease of median OS: 24.3 months versus 34.6 months, p = 0.041) without depending on the BRCA status. For the polymorphic marker rs17655 of the ERCC5 gene, significant difference in PFS was obtained in the period from 15.4 to 60.0 months of follow-up (the carrier of the C allele was associated with a decrease of median PFS: 20.0 months versus 35.2 months, p = 0.035). When considering the genotypes of the polymorphic marker of the ERCC5 gene differences were revealed between patients with the C/C genotype (M = 15.9 months) and two other genotypes (M = 33.6 months), p = 0.039. For the polymorphic marker rs1801270 of the CDKN1A gene significant differences in PFS were obtained in the period from 15.4 to 60.0 months of follow-up (for carriers of allele A, a decrease in median PFS was observed: 16.6 months versus 32.0 months, p = 0.046). For the polymorphic marker of the TP53 gene (rs1042522) a tendency to decrease OS for carriers of the C/C genotype was found seems promising for further study.Conclusion. The association of the studied polymorphic markers of the genes XRCC1 (rs25487), ERCC5 (rs17655) and CDKN1A (rs1801270) with PFS was revealed in patients with TNBC. Association with OS was obtained for the polymorphic marker of the XRCC1 gene (rs25487). These data may allow for further validation to individualize the treatment of this category of patients.

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.

Background. Treatment results for the patients with stage II–III triple negative breast cancer (TN BC) have to be improved. Not only the new treatment regimens, but new predictive and prognostic factors should to be developed.Materials and methods. We included 98 patients with stage II–III TN BC in our study. We studied efficacy and safety of PlaTax regimen (cisplatin 75 mg / m2 day 1 + paclitaxel 80 mg / m2 days 1, 8, 15, course every 4 weeks) in this cohort of patients. We assessed pathologic response, survival and factors, which were relevant for predicting response and prognose survival.Results. PlaTax regimen is characterized by high efficacy and tolerable toxicity. Clinical efficacy was 85.8 %, pCR achievement was 60.5 %, tpCR achievement was 58.1 %. The regimen has low haematological toxicity (neutropenia III–IV grades – 4.1 %); the most frequent adverse events were polyneuropathy (18.5 %) and decreased renal function (24.5 %). 3-year progression-free survival was 68.4 %, most of the relapses (92 %) occurred during first 2 years. 3 year overall survival was 77.6 %. The most relevant predictive factor was level of Ki-67 ≥50 % (pCR 38.5 % vs. 68.7 %, p = 0.038). pCR achievement was the most important prognostic factor, resulting in improved 3-year progressionfree survival (44.3 % vs. 89.1 %, p

The review article presents a summary of adverse drug reactions (ADR) in children, information about which was received in 1968–2018 in the International database VigiBase (Uppsala monitoring center, UMC). Of the 18.4 million Individual Safety Case Reports (ICSR) received over 50 years by VigiBase, 1.47 million ICSR contain information on the safety of pharmacotherapy in patients under the age of 18, including: 34 510 reports contain information on ADR in children under the age of 27 days, 415 678 — in children aged 28 days to 23 months, 613 676 — aged 2 to 11 years and 405 202 ICSR — in patients aged 12 to 17 years inclusive. During 2018 141 655 ICSR ADR of children in VigiBase was received. The most common reason for submitting reports on adverse effects in children was vaccines, antibiotics, non-steroidal antiinflammatory drugs, analgesics-antipyretics, anti-acne and valproic acid. The most common side effects of drugs in children were the following ADR: hyperthermia, rash, vomiting, nausea, urticaria, diarrhea, itching, headache, erythema at injection site, convulsion. Separate data on 6 age groups about 10 most frequent ADR in children and about 10 medicines which ICSR most often arrived in VigiBase for 50 years and for 2018 are given.

Background. Assessment of hormone receptor status plays a crucial role in treatment of patients with breast cancer. currently, clinicians are limited to determining the expression status of estrogen receptor (ER), progesterone receptor (pR) and HER2 only in primary breast cancer tissues, even in the presence of regional metastases.The purpose of the study was to review available data on heterogeneity of ER, pR and HER2/neu expressions in primary breast cancer and regional metastases.Material and methods. We analyzed publications available from pubmed, medline etc. using the keywords «discordance», «breast cancer», «locally advanced», «regional lymph nodes», «ER», «pR», and «HER2».Results. The clinical and prognostic role in assessing the heterogeneity of the receptor status of primary tumors and synchronous regional metastases, as well as the effect of detected discordance on treatment tactics was assessed.Conclusion. Data on the frequency of discordance in hormone receptor status between primary and metastatic breast cancer tumors and its effect on the further prognosis in breast cancer are still contradictory. However, the fact of the presence of such heterogeneity suggests that some patients with affected lymph nodes will have significant benefits from determining the status of steroid hormones and HER2 not only in the primary tumor, but also in the lymph nodes, since it will open up new opportunities for subsequent targeted therapy.

Objective: to evaluate the efficiency (morphological tumor complete regression (mCR), a clinical effect) and safety of the use of new anthracycline-free neoajuvant chemotherapy regimens (paclitaxel + vinorelbine and docetaxel + carboplatin) in combination with trastuzumab in patients with Stage IIIa-c breast cancer (BC) and Her-2 hyperexpression.Subjects and methods. The study enrolled 36 Stage IIIa–c BC patients receiving 4–8 cycles of a chemotherapy regimen of paclitaxel (100 mg/m2) + vinorelbine (25 mg/m2) (every 3 weeks) or docetaxel (50 mg/m2) + carboplatin (AUC 5) (every 3 weeks) in combination with trastuzumab.Results. The docetaxel (75 mg/m2) + carboplatin (AUC 5) + trastuzumab regimen demonstrated a high effectiveness with acceptable toxicity. Seventeen (58.8 %) patients achieved mCP. The clinical effect was 83.3 % (4 complete and 11 partial tumor regressions).The paclitaxel (135 mg/m2) + vinorelbine (25 mg/m2) (every 3 weeks) + trastuzumab regimen is efficacious and promising when the doses of the drugs are increased and granulocyte colony-stimulating factor used.

Before the development and implementation of the first PI3K inhibitor (alpelisib), the presence of a mutation in the PIK3CA gene had only prognostic value: it determined the unfavorable course of luminal HER2-negative metastatic breast cancer (testing for mutations was not part of routine screening methods). Achievements in the treatment of HR+HER2- mBC are primarily associated with the use of CDK4/6 inhibitors, which allowed not only a significant increase in the median progression-free survival while maintaining high quality of life, but also significantly increased overall survival of patients with luminal HER2-negative metastatic breast cancer. However, subgroup analyses demonstrate that the presence of the PIK3CA mutation is an independent factor in decreasing progression-free time and overall survival, even in patients treated with CDK4/6 inhibitors. Mutations of the PIK3CA gene are diagnosed in 30-40% of luminal metastatic breast cancer patients, they are associated with an increased risk of relapse and disease progression, are associated with a significant reduction in survival rates and treatment effectiveness, and determine the development of primary and secondary resistance to endocrine therapy. Standard endocrine therapy with fulvestrant combined with alpelisib has significantly improved treatment outcomes in patients with HR+HER2-metastatic breast cancer with the PIK3CA mutation who previously received treatment for advanced disease or had progression during adjuvant therapy. This combination is now included in all major international guidelines and is a priority therapy option. Testing for PIK3CA mutations is the current diagnostic standard in luminal HER2-negative mBC. The review presents an update of the main clinical trials with alpelisib, treatment results from real clinical practice, and also considers aspects of use in pretreated patients with different medical history. The article outlines the main recommendations for the prevention and correction of adverse events, and presents our own experience of using alpelisib in a patient with a classic course of breast cancer with a PIK3CA mutation.

Introduction. The presence of a germinal BRCA mutation occurs in 3–4% of all breast cancer (BC) patients with various biological subtypes, but significantly with a high frequency in patients with a triple negative biological subtype (in 10–20% of cases). For the treatment of patients with HER2-negative metastatic breast cancer associated with gBRCA mutation, the effectiveness of biologically targeted drugs from the group of PARP inhibitors (olaparib and talazoparib) has been proven.Purpose. Comparison of the results of our experience with the use of talazoparib in patients with HER2-gBRCA+ + mBC with the data of the EMBRACA registration study.Materials and methods. As part of the multicenter compassionate use program (CUP) with the support of Pfizer, 24 patients with HER2-negative metastatic gBRCA-associated mutation metastatic breast cancer (HER2-gBRCA+ breast cancer) received biologically targeted therapy with the PARP inhibitor talazoparib at a standard oral dose of 1 mg per day for vital indications . The average age of patients with HER2-gBRCAm+ breast cancer was 50 years (29–90 years).Results. Objective response (OR) was registered in 29% of cases, disease control (OR+stabilization) – in 71% of cases. The median progression-free survival (PFS) was 6.5 months (95% CI [3–10]). Objective response, disease control, and median PFS were evaluated depending on the biological subtype, the number of lines of previous therapy, and the presence of platinum-containing agents in the anamnesis.Objective response and disease control were evaluated depending on the biological subtype: in patients with ER+HER2-mBC versus patients with triple negative subtype, OR was 33% vs 22%, and disease control was 83% vs 61%, respectively. In the presence of < 3 vs ≥ 3 lines of therapy for metastatic disease in the anamnesis, OR was 31% vs 12.5%, disease control – 75% vs 50% of cases, respectively. In the presence or absence of platinum-containing agents in the anamnesis, OR was observed in 22% vs 33% of cases, and disease control – 67% vs 67%, respectively.In patients with the luminal subtype versus patients with the triple negative subtype, the PFS was 9 months vs 5 months, respectively (HR = 0.705; 95% CI [0.231–2.147]; p = 0.5208). Median PFS in the presence of

Understanding of cancer biology is at the cornerstone of design of new and effective treatment strategies. Identification of molecular drivers of tumor growth and progression allow identify right patient for the right treatment for personalized treatment plan optimization. Breast cancer (BC) encompasses a heterogeneous collection of neoplasms with diverse morphologies, molecular phenotypes, responses to therapy, probabilities of relapse and overall survival. Molecular and histopathological classification aims to categories tumors into subgroups to inform clinical decisions, to improve long-term treatment results and maintain the quality of life of this group of patients. Germinal mutation in the BRCA1/2 (BRCAm) genes in a tumor determines the hereditary predisposition, disease manifestation, therapeutic options and clinical efficacy. Therefore, patients withBRCAmBCrepresent a special subgroup requiring personalized treatment approach.Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is a targeted therapeutic agent that acts as inhibitor of single-strand breaks reparation, leading to their accumulation, conversion to double-strand breaks and eventually to cancer cell apoptosis. Olaparib is a first-in-class PARP-inhibitor with an outstanding antineoplastic activity known for some malignant tumors, demonstrates effectiveness and safety of therapy inBRCAmBCas well. The results of OlympiAD and LUCY trials are represented in the article. Subgroup analysis may define the patient population that would benefit from PARP inhibitors therapy.

Abstract. Phosphorilated polyprenols (PP) isolated from different sources are known to exert immunomodulating and antiviral activities. In this paper possible anti-inflammatory action of PP were studied using sensitive models of 5-lypoxigenase and 15-lypoxigenase activity inhibition, as well as a model of the hypostasis induced by the complete Freundt’s adjuvant, or carraginan. Also in vitro model of bronchospasm was used to study prospective broncholytic activity of PP. The latter was found to exert dose-dependent inhibitory effect upon both 5-lypoxigenase and 15-lypoxigenase activity. In the suspension cell culture significant inhibitory effect of PP upon leukotriens production was found even at a concentration of 5 mcg/ml; at concentration of 100 mkg/ml activity of the enzyme was suppressed almost to zero. In neutrophil cells cultivated on a collagenic substrate the significant inhibitory effect was also found at the concentration of 5 mcg/ml; 20 mcg/ml of PP reduced 5-LOX activity approximately 20-fold. In another protocol PP significantly inhibited 15-LOX activity. Thus, PP may be regarded as active inhibitor of both lipoxygenases. The PP exerted anti-inflammatory activity at both models of hypostasis, though it was weaker compared with indomethacin. Also PP was found to possess broncholytic activity in vitro in the bronchospasm model. Taking into account early established findings proving that PP may function as a physiological counterregulator of MIF (macrophage inhibitory factor), a major pro-inflammatory cytokine, our data prove that PP possess anti-inflammatory and broncholytic activities, which might be used for development of novel drugs for preventive care and treatment of bronchial asthma, inflammatory diseases and other pathologies.