Vol 27, No 11 (2020)

Triple negative cancer is a subtype of breast cancer (BC) characterized by the absence of the expression of estrogen and progesterone receptors, and the absence of HER2 overexpression and amplification. Triple negative breast cancer (TNBC) accounts for 10-20% of all breast cancer cases, and is somewhat more common in young patients compared to hormone receptor-positive disease and is characterized by a more aggressive course and early relapses. Despite the mass of studies on this topic, only chemotherapy remains the standard of treatment for this disease due to the absence of any targets on the surface of the tumor available for action. Taking into account the aggressiveness of the disease, many attempts are being made to improve the treatment outcomes of patients with TNBC. They include the use of post-neoadjuvant therapy, the addition of platinum supplements, the use of dose-dense regimens, the use of PARP inhibitors, and the search for various biomarkers to identify patients to whom additional therapies could be applied. This review represents the results of modern trials on these issues.

According to the St Gallen Consensus, endocrine-sensitive breast cancer (BC) is defined by the expression of positive steroid receptors. This type of cancer is the most common subtype of breast cancer. Available data suggest that the higher the ER and PR expression, the better outcome for patients with early and advanced breast cancer. Treatment for ER+ BC involves interventions (called endocrine therapy) that suppress estrogen production and/or directly affect the ER. Although endocrine therapy has significantly reduced recurrence and mortality from breast cancer, de novo and acquired resistance to this treatment remains a serious problem. A growing number of mechanisms of endocrine resistance have been reported, including somatic changes, epigenetic changes, and changes in the tumor microenvironment. The article provides a review of the literature on the signaling pathways that regulate tumor growth, the mechanisms of endocrine resistance development, and possible ways to its overcoming.

Background. Aflibercept is a recombinant protein for several growth factors that binds VEGFA and B, as well as PlGF, determining its antiangiogenic effect. Objective. Clinical evaluation of the efficacy and safety of aflibercept in patients with metastatic colorectal cancer (mCRC). Methods. The data on the treatment of 50 patients with initially metastatic and generalized CRC were analyzed. The study included patients in satisfactory general condition (ECOG <2), after progression on oxaliplatin-containing chemotherapy; in the case of generalization of the process, the time to progression was at least 6 months after completion of the adjuvant treatment. The drug was administered intravenously at a dose of 4 mg/kg once every 14 days in combination with the FOLFIRI regimen. The direct clinical effect, overall and progression-free survival, and adverse events associated with antitumor therapy were evaluated. Results. The objective effect on the background of the therapy was 16.7%, tumor control was achieved in 70.9% of cases. When aflibercept was prescribed as the 2nd-line therapy, a more frequent registration of the objective effect was noted than with its use as the 3rd and subsequent lines. The median time to disease progression was 6.3 (2-18) months, and the median overall survival - 17.1 months (2-48) months. Arterial hypertension was the most common adverse event, which caused the cancellation of aflibercept in 14% of cases. Conclusion. The obtained objective effect and relapse-free survival with the use of aflibercept in patients with CRC were comparable with the data of previous studies, while the earlier drug prescribing, the higher the percentage of objective responses to treatment. Data on overall survival exceeded the results of a registration study for the general patient population. This is probably due to the fact that the study group did not include patients with adverse prognostic factors such as low functional status and progression after adjuvant treatment for 6 months. Of the clinically significant manifestations of toxicity, arterial hypertension should be noted. A personalized approach to the selection of patients for therapy with aflibercept, taking into account risk factors for the development of 3-4 degree non-hematological adverse events, is likely to reduce the number of complications without loss of effectiveness.

Background. Cervical intraepithelial neoplasia (CIN) occurs in 1.3 to 2.7 cases per 1000 pregnancies, and the incidence of cervical cancer (CC) is 0.1-12 per 10,000 pregnancies. Changes in the expression of genes of various signaling pathways can serve as a prognostic factor for the transition of CIN to cancer. However, these processes are insufficiently studied, especially in pregnant women, which served as the basis for this study. Objective. Determination of the expression of proliferation- and apoptosis-related genes in pregnant women infected with human papillomaviruses (HPV) and their role in predicting the progression of cervical neoplasia. Methods. An open-label observational non-interventional cohort clinical study was conducted. 82 pregnant women infected with HPV were examined. Control group consisted of 25 pregnant women without HPV. All participants underwent general clinical examination, Kvant-21 test to determine the types of HPV, cytological examination of cervical smears, determination of the mRNA expression of the VEGFA, TGFb, BCL-2, BAG1, BAX genes in the epithelial cells of the cervical canal by the real-time polymerase chain reaction. Results. The expression of proliferation-related genes - VEGFA (in the presence of HPV-16, -39, and -58), TGF-b (HPV-16, -33, -39 and -59), BCL-2 (HPV-16, -52 and -58), BAG-1 (HPV-16, -31, -35, -58, and-87) was significantly higher compared to control. With LSIL (low grade squamous intraepithelial lesion), the expression of the VEGFA gene increased, and with HSIL (high grade squamous intraepithelial lesion), expression of all genes (except BAX) increased. So, the ability of some HPV types to change the expression of proliferation-related genes was revealed, but no changes in the expression of the BAX gene, which controls apoptosis, were observed. Conclusion. The most pronounced ability to change the expression of proliferation-related genes is possessed by HPV-16 and -58. In LSIL, an increase in the expression of only the VEGFA gene was revealed, in HSIL - increase in expression of all genes characterizing the proliferative potential. No changes in the expression of the BAX gene, which stimulates apoptosis, were found in HPV-infected pregnant women. The results of the study indicate the possibility of using these markers in predicting the progression of cervical lesions, but further research is required.

Background. Until now, there is no single concept in the complex treatment of malignant tumors of the duodenum due to the low incidence of morbidity. Description of the clinical case. The article describes the case of a 27-year-old female patient with a history of gastrointestinal bleeding of unknown etiology. A tumor with a complicated course in the form of profuse bleeding was not visualized during diagnostic procedures. It was associated with the feature of the histostructure, the origin of the tumor from the muscular structure of the duodenal wall and extraorganic growth without damage to the mucous membrane. Conclusion. The case described is a vivid example of the complexity of diagnosis of tumors of the hepatopancreatoduodenal zone, demonstrating a high percentage of diagnostic errors in the complicated course of the tumor process in the form of profuse bleeding.

Background. Colon cancer is one of the most common malignancies worldwide. At the same time, about 30% of patients at the time of diagnosis have a disseminated tumor process. Despite the progress in pharmacotherapy of patients with metastatic colorectal cancer over the past 15 years, 5-year survival is still relatively low. Panitumumab, a fully human monoclonal antibody that blocks the epidermal growth factor receptor (EGFR), significantly increases the life expectancy of patients with this pathology. The drug is approved for the treatment of RAS wild-type advanced colorectal cancer in combination with chemotherapy as the first- or second-line of therapy or as monotherapy for chemoresistant cancer. Description of the clinical case. We present a clinical case of the treatment of a 71-year-old patient with disseminated sigmoid colon adenocarcinoma and progression after three lines of therapy. The patient underwent 12 cycles of chemotherapy according to the FOLFOX-6 regimen in combination with panitumumab. The maximum treatment effect was partial regression. Conclusion. Our clinical experience demonstrates that therapy with panitumumab in combination with FOLFOX-6 chemotherapy allows to achieve an objective effect, increase the time to progression and overall survival in previously treated patients with metastatic colon cancer.

Background. Metastatic muscle damage is a rare manifestation of malignant neoplasms with a poor prognosis, including colon cancer. Until now, due to the low incidence of cases with metastasis to the ileo-psoas muscle, there is no single concept in the complex treatment of these distant manifestations of the disease. Description of the clinical case. The article describes the case of a 33-year-old patient with a history of combined treatment of colon cancer in 2017. The progression of the disease began 5 months after the end of chemotherapy. Morphological examination of the ileo-psoas muscle confirmed metastasis of colorectal adenocarcinoma. The patient underwent IMRT-SIB radiation therapy using the Elekta Synergy apparatus. No signs of progression are observed for 7 months. Conclusion. The prognosis for metastatic muscle lesions in colon cancer is generally poor, with a median survival of 5 to 12 months. In this clinical case, we describe the possibilities of individual selection of surgical and radiation treatment for rare forms of colon cancer metastasis.