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BACKGROUND: Surgical treatment of breast cancer plays a major role in the combined and complex treatment of patients. The purity of the examined edges of the resected breast tissue is the main indicator of the reliability of the breast-conserving surgery and one of the main factors in the development of local recurrence. Neoadjuvant (preoperative) systemic therapy allows evaluating the effectiveness of therapy in vivo and reducing the size of the initial formation, both in locally advanced and resectable forms of breast cancer. The main advantage of this treatment is the ability for surgeons to perform breast-conserving surgery to improve patients quality of life and aesthetic outcomes without compromising disease-free and overall survival. AIM: To study the clinical and pathological characteristics and analyze of the breast-conserving surgery in patients with breast cancer after neoadjuvant chemotherapy. MATERIALS AND METHODS: 156 performed breast-conserving surgery after neoadjuvant chemotherapy were analyzed. Breast-conserving resection implied radical removal of the residual tumor node within healthy breast tissues with the achievement of negative resection margins. If pathologists detected stained invasive cells/cancer in situ in a formalin-fixed preparation, a second surgical intervention was performed. RESULTS: Of the 156 studied anatomical preparations after breast-conserving surgery, a positive margin was found in 4 (2.56%) cases. In 4 patients, positive margin was represented by ductal carcinoma in situ. According to the results of trephine biopsy, no intraductal component was found before neoadjuvant chemotherapy. The greatest length of the ductal carcinoma in situ section is 2.2 mm. In 3 cases, the distance to the stained resection margin of the micropreparation was 1 mm. As a result of repeated pathomorphological examination of pre-cut margins after surgical intervention, cancer in situ was not found. CONCLUSIONS: The ongoing neoadjuvant systemic therapy for breast cancer with a partial or complete response of the tumor increases the percentage of breast-conserving surgery performed in patients who initially belong to the group of radical mastectomy, but who want to save breast tissue.

BACKGROUND: Neoadjuvant systemic therapy for triple-negative and HER2-positive breast cancer can achieve a complete pathologic response in approximately 60% of patients. Pathological complete response to neoadjuvant systemic therapy is a predictive factor consistent with a positive prognosis which can be accurately determined by percutaneous vacuum aspiration biopsy. AIM: To evaluate the amount of surgery in the group of patients with triple-negative and HER2-positive early breast cancer whose complete pathologic response was confirmed by vacuum aspiration biopsy and who did not undergo standard surgery. MATERIALS AND METHODS: The following single-centre study has been conducted in the Russian Federation. Women aged 18 years old and older with unicentric (cT1-2N0-1M0 by classification TNM) triple-negative or HER2-positive breast cancer with complete clinical response after neoadjuvant systemic therapy according to imaging diagnostic methods. The patients underwent vacuum aspiration biopsy on the mammary gland under ultrusound control with standard amount of surgical intervention on the axillary region. In case when no invasive or in situ disease was detected, no further breast surgery was performed and the patients underwent standard radiation therapy. The survival with no tumor relapse in the ipsilateral mammary gland was assessed as the primary endpoint. The study is registered on сlinicaltrials.gov, NCT04293796. RESULTS: Between June 2020 and May 2022, twenty-seven (84.4%) patients (all women; mean age 47.5 (3268) years) were enrolled in the study and underwent visually controlled vacuum aspiration biopsy. The average initial tumor size was 20.5 (735) mm. 7 (25.9%) patients initially had metastases in the axillary lymph nodes confirmed by puncture biopsy; 15 (55.6%) patients had HER2-positive breast cancer, and 12 (44.4%) had triple-negative breast cancer. A study of vacuum aspiration biopsy samples showed that 6 (22.2%) patients had a residual tumor, and 21 (77.8%) patients achieved complete pathologic response (95% confidence interval 53.2 to 81.4). At a median follow-up of 12.4 months, there were no tumor relapses in the ipsilateral mammary gland in 21 patients with complete pathologic response confirmed by vacuum aspiration biopsy after neoadjuvant systemic therapy, as well as other relapses or progression of the disease. CONCLUSIONS: The patients with a complete pathologic response, which is confirmed by the vacuum aspiration biopsy method, who refused to perform surgery on the mammary gland do not demonstrate worse results with a short period of observation. However, additional prospective clinical studies are needed.

BACKGROUND: BRCA-associated triple-negative breast cancer does not only have a better overall survival rate, but also a longer recurrence-free period in compatison to patients with sporadic breast cancer. BRCA-associated triple-negative breast cancer shows high sensitivity to chemotherapeutic agents, but the benefit of systemic neoadjuvant therapy for patients with tumor size T1 in triple-negative breast cancer is unclear. AIM: The aim of the study is to determine the recurrence rate in the patients with BRCA-associated triple-negative breast cancer and to determine the recurrence rate for the group of patients with tumor size T1, depending on the initial treatment. MATERIALS AND METHODS: The study includes the data of 129 patients diagnosed with BRCA-associated triple-negative breast cancer treated in the period from 2010 to 2022 at the Department of Breast Tumors of the N.N. Petrov National Medical Research Center of Oncology. All the patients have been divided into two groups depending on the initial treatment. Group I included 93 (72.1%) patients whose treatment was started with systemic neoadjuvant therapy, group II, whose initial treatment involved surgery, included 36 (27.9%) patients. RESULTS: In group I, the number of recurrences was 22 (23.6%), and in group II 6 (16.6%). Depending on the pathomorphological response to systemic neoadjuvant therapy, the patients of group I have been separated: in the group of patients with a complete pathomorphological response, the number of relapses was 6 (13.3%), and in the group of patients with a partial pathomorphological response 16 (33.3%). A comparative analysis of 2 groups with tumor size T1 has shown that in group I the number of patients with tumor size T1 was 11 (11.8%) cases, and in group II 16 (44.4%). Subgroup comparative analysis in group I, taking into account tumor size T1, has shown that recurrence has not been observed when a complete pathomorphological response was achieved in 8 (17.7%) patients, and in the group with partial pathomorphological response in 3 (6.25%) patients with tumor size T1. A relapse has been observed in 1 (2%) case. With clinical tumor size T1 (n = 16), there was no recurrence in group II. CONCLUSIONS: Patients diagnosed with BRCA-associated triple-negative breast cancer remain at a high risk of recurrence at a later stage of the disease, but this does not apply to patients with a tumor size T1 since the difference in relapse-free survival [AP1] between patients, whose treatment was started with neoadjuvant systemic therapy and patients, whose initial treatment involved surgery % with a clinical tumor size T1, is not confirmed.

Aim. To increase the effectiveness of neoadjuvant chemotherapy in patients with locally advanced gastric cancer by correcting nutritional deficiency. Materials and methods. Of 200 patients with locally advanced gastric cancer (mean age 57.2 years (46.168.3), 100 patients received neoadjuvant chemotherapy with nutritional support from 2018 to 2020. One hundred patients received neoadjuvant chemotherapy without nutritional support from 2013 to 2018 (historical control). The incidence of nutritional deficiency before treatment in the neoadjuvant chemotherapy + nutritional support group was 54%, and in the neoadjuvant chemotherapy only group it was 47%. Nutritional status was assessed using anthropometry, questionnaires (NRS-2002, MUST, GLIM), dynamometry, blood tests, bioimpedance. Complications according to NCI CTCAE v5.0; оbjective response rate according to RECIST 1.1; pathomorphological regression according to the JGCA classification (2017); 2-year event-free survival were assessed. Results. The frequency of nutritional deficiency before the start of treatment in the neoadjuvant chemotherapy + nutritional support group was 54%, in the neoadjuvant chemotherapy only group 47%. After the completion of neoadjuvant chemotherapy in the group neoadjuvant chemotherapy + nutritional support the frequency of nutritional deficiency was 1%, in the group neoadjuvant chemotherapy only without nutritional support 62%. In patients with nutritional deficiency in the neoadjuvant chemotherapy + nutritional support group, partial regression was registered in 51.9% of cases, in the neoadjuvant chemotherapy only group it was 27.6% (p0.05). There were no differences in the frequency of pathological response. 2-year event-free survival in patients without nutritional deficiency in the group neoadjuvant chemotherapy + nutritional support was 100%, in the neoadjuvant chemotherapy only group it was 68.5% (p0.001); in patients with nutritional deficiency 72,5 and 60.6% respectively (p0.05). Conclusion. Nutritional deficiency is an important predictive and prognostic marker of the efficacy of neoadjuvant chemotherapy in the treatment of locally advanced gastric cancer. Comprehensive diagnosis of nutritional status and nutritional support can improve the results of neoadjuvant chemotherapy in patients with locally advanced gastric cancer.

Introduction: The effects of chemotherapy are known to depend on the time of administration. Circadian rhythms are disturbed in tumors and in tumor bearers. Agents involved in controlling the circadian rhythms (chronobiotics) potentially can modify the outcomes of chemotherapeutics administered at different times of the day. Pineal hormone melatonin (MT) is a prototypic chronobiotic. Objective: The aim of the study was to investigate if MT can affect efficacy or toxicity of chemotherapy drugs administered at the extreme time points of the working day of hospital personnel. Methods: Cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and adriamycin and docetaxel (AT) cytotoxic drug combinations were administered on day 0 at 11:00 a.m. or at 5:00 p.m. (UTC+03:00) to 6-month-old female HER2/neu transgenic FVB/N mice bearing mammary adenocarcinomas. Some mice were additionally provided with MT in drinking water (20 mg/L) at night 1 week before or 3 weeks after treatment or during both periods. Tumor node sizes, body weight, and blood cell counts were determined right before treatment and on days 2, 7, 14, and 21. Results: Significant decrease in the mean tumor node volume was found by days 14 and 21 upon all CAF and AT treatment schedules, except in animals treated with AT at 5:00 p.m. without supplementation with MT. In the latter case, mean tumor node volume on day 21 was the same as in the control. Supplementation of AT administered at 5:00 p.m. with MT improved the tumor response. CAF and AT regimens supplemented with MT also augmented the number of tumor nodes that did not increase by more than 20% by day 21 as compared to CAF or AT alone, respectively. This effect was significant in groups treated with AT at 5:00 p.m. and consistent upon other schedules. On day 7, leukopenia and anemia were registered in groups treated with CAF regimen; however, blood cell counts normalized by day 14. Both CAF and AT were associated with drop in the body weight registered on day 7. Supplementation with MT did not affect changes of the body weight and blood counts. Conclusions: MT supplementation to cytotoxic drugs can improve antitumor response, especially if it is blunted because of an inappropriate time of administration.

e12551 Background: A grade in breast cancer is the strongest prognostic factor. In the new edition of the AJCC 8th, the tumor grade is one of the criteria that determines patients with breast cancer in the prognostic groups. According to the Nottingham system the mitotic count (MC) mostly determines the grade. Interobserver reproducibility for MC is not as good as for IHC marker phh3. The group of triple-positive breast cancer (TPBC) is characterized by the presence of a crosstalk mechanism between the signaling pathways of ER and HER2, which leads to the development of resistance to therapy. However, according to the 8th AJCC, patients with ER+/HER2+ belong to a more favorable prognostic group. Methods: We selected 284 patients with early BC who received treatment at our centre from 2012 to 2020 and didn’t receive presurgical therapy. The patients were divided according to the surrogate subtype into triple-positive (n = 90) and other subtypes (n = 194). The Ki-67, the number of nuclei of tumor cells stained with anti-phh3 antibody, the cell density of the tumor per 1 mm2 and the number of phh3 + per 1000 tumor cells were assessed. Results: Visually accessed number of mitoses was grade 3 in 30% of tumors in the TPBC group and 29% in the second group. There was no statistically significant difference in the Ki-67 index of proliferative activity in the two studied groups. In the TPBC group the median Ki-67 was 16.8%, in the second group - 18.3% (p = 0.376516), while the groups differed significantly in terms of the phh3 index (the median in the TPBC was 23.7/mm2, the median in the second group - 16.06/mm2, p = 0.024703). The groups also significantly differed in the number of nuclei of tumor cells that directly entered the mitotic phase (5.1/1000 nuclei in the TPBC group versus 3.2/1000 nuclei in the second group, p = 0.003901). Conclusions: Despite similar indices of proliferative activity in the TPBC and non-TPBC groups, mitotic activity and the number of directly dividing tumor cells in the TPBC group are significantly higher than in the rest of the BC population. Considering the criteria for assessing phh3 (MC 1 < 4/mm2, MC 2 2 4 to 7/mm2, MC 3 > 7/mm2), most TPBCs will have a histological malignancy grade of 3, which according to AJCC 8th places them in the group of poor outcome. We suggest that these differences may be due to the crosstalk mechanism. The second conclusion of our study is the fact that Ki-67 is a poor predictor of the MC.

This article reflects the main stages of development of high-dose chemotherapy with autologous stem cell as an effective method of treatment of various hematological, oncological and hereditary diseases. It describes the development of the research beginning with the discovery of the stem cells by A.A Maksimov to the contemporary ways to elaborate them into blood; it reflects the basic mechanisms of action of different groups of drugs on complex biochemical cascades close interaction with hematopoietic cells of the bone marrow microenvironment, which, in turn, determines their further destiny and lead to a loss of hematopoietic stem cells in peripheral blood. However, in spite of the current approaches to improve ways of harvesting stem cell, there is a certain percentage of patients in whom it is impossible to collect adequate for quick recovery of hematopoiesis after high-dose chemotherapy number of cells. This percentage will vary according to various literature sources, 5 to 40 %. Therefore, the development and application of new drugs, growth factors and cytokines, which would overcome the problem of poor mobilization is an important issue in modern medicine. The article presents data on the use of a new mobilizing agent plerixafor, the use of which in practice improves the successful mobilization of 40 %. The study of its combined action of various growth factors, including pegylated filgrastim, is a promising direction, because can be a good option for patients with poor mobilization activity for which the previous regimen mobilization proved ineffective. The research of plerixafor interacting with various growth factors including pegylated filgrastim is considered to be the most promising direction. This method is believed to help patients with low mobilizing activity where all other means have failed to improve it.

11075 Background: While a number of antigens are known to be expressed in soft tissue sarcomas, little is known about the prognosis of patients with such tumors. Recent data have demonstrated immunologic activity in sarcoma patients expressing the NY-ESO antigen, found positive in 20-80% cases. MAGE A3 has also recently attracted attention with regard to soft tissue sarcomas. In our study we aimed to assess any association between antigen expression and prognosis. Methods: In a case-control study we retrospectively collected data from a prospective database of all 137 patients with sarcomas receiving first line therapy in the Petrov Research Institute of Oncology in Saint-Petersburg. All cases were morphologically verified, with mRNA expression of NY-ESO-1, MAGE A3, PDGFR A, PDGFR B, beta-tubullin and top2alpha additionally being tested by quantitative real-time PCR in a subset of patients. The log-rank test was applied to compare Kaplan-Mayer estimates of progression-free (PFS) and overall survival (OS) by univariate analysis. Hazard ratios were derived after adjustment for age, gender, several covariates for type of chemotherapy and disease stage with two-sided probability at a significance level of 0.05. Results: The positive rate for expression of NY-ESO was 20% (11/43).Only NY-ESO was significantly associated with PFS (p < 0,001), with a median durations of 10, 4 and 7 months for positive, negative and not tested for NY-ESO expression, respectively. The adjusted hazard ratio (HR) for NY-ESO positive patients was 2.2 (95%CI, 1.2;4.2) compared with their negative counterparts, The HR for patients not tested for NY-ESO was 2.0 (95%CI, 1.3;3.0). Among other covariates, only a combination of drugs was associated with a lower risk of progression (HR, 0.7 95%CI, 0.4;0.98) , as compared to those receiving a single chemotherapy agent. Conclusions: This first report showing prognostic significance of NY-ESO expression in soft tissue sarcoma patients, suggests that research should be focused on targeting this antigen. Participation in clinical trials for patients with positive NY-ESO expression is highly recommended, because of poor survival regardless of the type of standard treatment.