Background: The aim of this prospective randomized trial was to investigate the influence of metformin on the effectiveness of neoadjuvant systemic therapy in breast cancer patients with metabolic syndrome. Patients and methods: The study included 72 patients (from 31 to 77 years of age) who received neoadjuvant systemic treatment for stage II-III breast cancer at the National Medical University named after O.O Bogomolets, Municipal City Clinical Oncological Center, Department of Oncology, Kyiv during 2010-2014. Metabolic syndrome was diagnosed in all patients according to the International Diabetes Federation criteria. They were divided in two groups: group 1 that included 36 patients with metabolic syndrome and breast cancer who did not intake metformin during neoadjuvant systemic therapy, and group 2 that included 36 patients with metabolic syndrome and breast cancer who received metformin with neoadjuvant systemic therapy. Results: Complete clinical response was identified in 2 (6%) patients from group 1 and 10 (27.5%) patients from group 2. Overall clinical response rate (cCR + cPR) was achieved in 28 (77.5%) patients treated with metformin compared to 9 (25%) patients from group 1. A stable disease was observed in 19 (53%) patients who were not taking metformin. The rate of pathological complete response was 26.5% (9 patients) in the metformin group and 6% (2 patients) in the non-metformin group. Conclusions: Combined neoadjuvant systemic anticancer therapy of breast cancer patient with metabolic syndrome with metformin has a higher clinical and pathological overall response rate than treatment without metformin.
Background: Recent advances in the treatment of breast cancer (BC) have been related to the personalization of therapy. The methylation status of the promoter regions of tumor suppressor genes such as BRCA1 and BRCA2 is supposed to be useful as a prognostic factor in BC patients. Aim: To investigate the frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes in tumor tissue of BC patients, and the relation of hypermethylation to the clinical course of the disease. Materials and Methods: Molecular genetic studies were performed on 50 BC tissue samples in order to determine the methylation status of the promoter regions of the BRCA1 and BRCA2 genes. Results: Hypermethylation of the BRCA1 promoter region was detected in 34% of BC cases, hypermethylation of the BRCA2 promoter region — in 50% of cases, and hypermethylation of the promoter region of both genes — in 20% of cases. A significant increase in the incidence of hypermethylation of the BRCA2 promoter region was found in the group of patients older than 56 years, mainly in patients with triple-negative breast cancer and without family history of BC. Conclusions: The high frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes, as well as their co-methylation in tumor tissue of BC patients has been detected.
Summary. The gold standard for managing muscle-invasive bladder cancer is radical cystectomy (RCE). The RCE is a treatment, which carries high burden of perioperative morbidity and mortality. As biomolecular markers make muscle-invasive high-grade bladder cancer (HGBC) an entity different from non-invasive papillary disease, we tested a hypothesis that alternative bladder preserving surgery (BPS) approaches, such as partial cystectomy and transurethral resection of the bladder would not compromise the oncological results of treating HGBC in selected patients. Aim: To study the cancer specific survival of HGBC patients depending on the mode of surgical treatment — RCE, partial en-block cystectomy, and transurethral resection of the bladder in the practice of the Departments of Urology and Oncology of Bogomolets National Medical University, and to assess the prevalence of bladder sparing surgical management of HGBC in local practice as a part of trimodal treatment approach to bladder preservation. Materials and Methods: Retrospectively we studied the medical records of 3597 urothelial bladder cancer patients, of whom 346 (10%) had high-grade disease and who underwent surgical treatment in 2004–2017. All patients were studied with contact computed tomography of the chest, abdomen, pelvis, and biopsy of the tumor. Based on the results of the diagnostic workup the choice of surgical treatment between RCE, partial cystectomy and transurethral resection was made considering the size of the tumor, location of the tumor in the bladder in relation to the bladder neck, and technical and oncological feasibility of performing the bladder sparing surgery. Kaplan — Meier survival curves were built to compare the results of survival per cancer stage and type of surgical treatment. Survival data of the patients were collected from the cancer registry maintained at the Kyiv Municipal Clinical Oncological Center. Results of data analysis were controlled for confounding parameters, such as adjuvant treatment: perioperative radiotherapy, and chemotherapy. Results: Median follow-up was 93 months (1–226 months). Males were 276 (80%). Average age at diagnosis was 62 ± 4.5 years. By the time of the study 61% of patients have died due to the progression of the disease. All patients with stage I disease (7% or 24 patients) were managed with bladder-sparing surgery. In muscle-invasive disease (309 patients), the RCE was performed in 109 (35.3%) patients, partial cystectomy was performed in 79 (25.6%) patients, and transurethral resection — in 121 (39.1%) patients. The overall 5-year survival of HGBC patients after radical surgical treatment (RCE/BPS) for stage I patients was 0%/83%, for stage II — 43%/58%, for stage III — 37%/42%, and for stage IV — 10%/40%. A total of 44 patients (12.7% of all treated, and 19.6% of treated with bladder sparing) received postoperative radiotherapy after bladder-sparing surgery. A total of 14 patients (4% of all treated) received postoperative chemotherapy. Conclusion: Bladder sparing surgery (partial en-block cystectomy, and transurethral resection of the bladder) in selected patients is not inferior to RCE in terms of cancer-specific survival when treating patients with HGBC of all stages. The bladder sparing surgery was performed in 64.7% of patients with high grade bladder cancer. Utilization of adjuvant treatment is low, 12.7% for postoperative radiotherapy, and 4% for perioperative chemotherapy
Summary. Brain metastases of solid tumors are the most common intracranial neoplasms in adults. We provide a short overview of the role of the blood-brain barrier in the pathogenesis of breast cancer brain metastases, and the effectiveness of systemic anticancer therapy in the treatment of such patients.
Background. The aim of the research was to estimate the frequency of the locoregional breast cancer recurrence appearance, the recurrence-free period continuance, and the 3- and 5-year survival depending on the scope of the surgical intervention, menstrual profile, and histological and molecular-biologic characteristics of the primary tumor. Patients and Methods. Among 218 patients with a breast cancer, 99 patients had breast-conserving surgery (BCS) and 119 underwent radical mastectomy (RME); all patients had regional lymphatic nodes dissection. The size and the primary tumor differentiation degree, metastasis presence in the regional lymph nodes, ER expression, PR, and Her/2neu were assessed as the prognostics factors. Results. It was defined that the locoregional recurrence appearance frequency in patients with BCS turned out to be 13%, and in patients after RME it turned out to be 9%; the recurrence-free period continuance was 53 ± 8 months and 56 ± 10 months, respectively. Conclusions. The locoregional cancer recurrence frequency is higher in women with the menstrual function being preserved at the moment of the primary tumor detection than in postmenopausal patients and also in patients having the hyperexpression of the Her/2neu. The ipsilateral cancer recurrence decreases the 3-year survival by 7,1% and the 5-year one by 20,3%, respectively.
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