659 Background: Gastrointestinal (GI) neuroendocrine carcinomas (NEC) are rare tumors and account for 3% of all NECs. Despite the differences in genetic characteristics, treatment principles of GI NECs are extrapolated from lung NECs. The standard first-line therapy is platinum and etoposide-containing regimens, which allow to achieve a median PFS of 5-6 months. A small retrospective study demonstrated the potential effectiveness of the mFOLFIRINOX regimen with a median PFS of 5.4 months, despite that the majority of patients (pts) received this regimen as second or subsequent lines. The aim of this study is to evaluate mFOLFIRINOX +/- somatostatin analogues (SA) efficacy in GI NEC subgroup. Methods: This prospective, single center phase II study used a two-stage Simon design. The primary endpoint is disease control rate (DCR) ≥ 6 months. Statistical hypothesis: investigated therapy improves DCR compared with historical control from 50 to 70%. Secondary endpoints are progression-free survival (PFS), overall survival (OS), objective response. At the first stage, enrollment of 16 pts was planned (α=0.05, power 80%). If a disease control ≥ 6 months was achieved in at least 9 of the 16 pts, it was planned to continue enrollment up to 39 pts. Here we present results of the first stage of this study. Inclusion criteria: pts ≥18 y.o. with histologically confirmed advanced GI NEC or neuroendocrine tumor (NET) G3 ki67≥55%; ECOG 0-2. Recruitment of pts was carried from 2019 to February 2024. Results: The study included 16 pts, 12 male and 4 female. The most common sites of primary tumor are stomach (N=8, 50%) and pancreas (N=5, 31.3%). 10 (62.5%) pts had large cell carcinoma, 1 – small cell carcinoma (6.3%), 5 (31.3%) – NET G3. The median ki-67 was 70% (40-95%). 15 pts (93.7%) had IV stage, 1 (6.3%) – III. The most common site of metastases is liver – 11 (68.8%), more than half of pts have isolated metastases in liver (N=9, 56.3%). ECOG status was evaluated as 0-1 in 15 (93.7%) cases. Majority of pts (N=14, 87.5%) received mFOLFIRINOX as first line therapy. 7 pts (46.7%) had positive expression of SSTR-2A or -5 and received concurrent treatment with SA. ORR was 62.5% (N=10/16), stable disease – 37.5% (N=6/16). DCR ≥ 6 months was 93.7% (N=15). With a median follow-up of 13.2 months, median PFS was 10.8 months (95% CI 7.57-14.1). One pts had serious adverse event - myocardial infarction, no grade 5 toxicity was observed. Conclusions: Chemotherapy with mFOLFIRINOX showed promising results in GI NECs or NETs G3 ki67≥55% treatment. Primary endpoint was met, enrollment of patients in the study continues.

The widespread use of anti-HER2 drugs has fundamentally changed the fate of patients with both early and metastatic HER2-positive breast cancer (BC). The results of clinical studies demonstrate a significant increase in the frequency of achieving complete pathological response (pCR) and, as a consequence, improved survival rates when using the combination of docetaxel + carboplatin + trastuzumab + pertuzumab (TCHP) in neoadjuvant chemotherapy for HER2+ breast cancer, which is reflected in modern domestic and international guidelines. The purpose of this study was to evaluate the effectiveness of the TCHP regimen, as well as to identify independent clinical and morphological factors in achieving pCR. The study included 234 patients with HER2-positive breast cancer of stages II and III who received TCHP regimen in neoadjuvant setting, 233 were operated. The rate of achieving complete pathomorphological response (pCR, RCB 0) was 63 %, in the nonluminal HER2-positive subtype – 76 %, in the luminal HER2-positive subtype – 55 %. Predictors of pCR were the absence of hormonal receptors in the tumor (OR = 1.72; 95 % CI: 1.17–2.54; р = 0,01), as well as a high (>50 %) Ki-67 proliferation index (OR = 1.4; 95 % CI: 1.01–1.98; р = 0,05). The use of granulocyte colony stimulating factor as primary prevention has reduced the risk of febrile neutropenia and mucositis. Further observation of patients will allow us to evaluate the long-term results of neoadjuvant therapy for HER2-positive breast cancer using the TCHP regimen in our population.

Introduction: Pheochromocytoma (PC) and paraganglioma (PG) are rare neuroendocrine tumors derived from adrenal chromaffin cells. The main options of systemic therapy for PC / PG are alkylating agent-based chemotherapy (ChT) and targeted therapy with sunitinib. There are no comparative data on the efficacy of these options, which became the purpose of this study.Materials and methods: This retrospective single-center study included patients over 18 y. o. who received ChT or targeted therapy for the first line treatment for metastatic PC / PG from September 2015 to August 2023.Results: The study included 33 patients (pts) who were divided into two groups — ChT (N = 18, 54.5 %) and targeted therapy (N = 15, 45.5%). In the ChT group, 12 pts (66.7%) received CVD regimen, 6 (33.3%) — temozolomide. In the targeted therapy group, 10 pts (66.7%) received sunitinib, 4 (26.7%) — pazopanib, and 1 (6.7%) — everolimus. Concurrent somatostatin analogues therapy was prescribed in 12 (66.7%) and 10 (66.7%) pts in the ChT and targeted therapy groups, respectively. Both groups were comparable by all main characteristics. Objective response was achieved in 11.11 % (N = 2) and 6.67 % (N = 1) [p=0.99], disease control > 6 months — 61.11 % and 60% (p = 0.99), biochemical response — 36.36% and 30% (p = 0.9) in the ChT and targeted therapy groups, respectively. Median PFS was 12.7 (2.9-22.3) in the ChT versus 12.9 months (2.3-26.5) in the targeted therapy group (p = 0.55). Median overall survival was not reached in both groups.Discussion: According to comparable efficacy of both treatment options and the indolent course of PC / PG, most patients do not require ChT in the 1st line of treatment. While choosing the 1st line therapy it is necessary firstly to take into account the safety profile of the drugs.

Abstract Introduction: The efficacy of dose-dense (dd) adjuvant chemo has been proved in numerous clinical trials and meta-analysis. However, it remains unclear whether the intensification of AC (doxorubicine/cyclophosphamide) regimen affects the rate of pathological complete response (pCR) in HER2+ subtype, since the efficiency of thе ddAC-THP (docetaxel/trastuzumab/pertuzumab) regimen with dual anti-HER2-blocade in the neoadjuvant (NA) setting has not been assessed. Anthracycline (A)–containing and A-free regimens (TCHP -docetaxel/carboplatin/trastuzumab/pertuzumab) are considered equivalent, although there are no direct comparative studies to date. Methods: The aim of the study was to assess the rate of pCR of ddAC (once every 2 weeks)-THP NA regimen in comparison with ACq3w (once every 3 weeks)-THP and A-free TCHP regimen in HER2+ stage II-III breast cancer (BC). The study included patients with early HER2+ BC who received NA chemo in a single center from Jan 2017 to Nov 2022. Statistical hypothesis. The study has a 2-step design. It is assumed that the rate of pCR with ddAC will be ≥65%, and with ACq3w≤50%. With a unilateral type I error (α) = 0.05 and a type II error (β) = 0.2, 170 patients should be included in each group. In the absence of significant differences between ddAC and 4ACq3w, groups may be merged into one cohort and compared with TCHP group. It is assumed that A-containing regimens (H1 - pCR 55%) are not inferior to A-free regimen (H0 - pCR 55%). A non-inferiority design is planned, with delta 15%, type I error (α) = 0.05 and type II error (β) = 0.2, 173 people in each group should be included. Here we present preliminary results. Results: A total of 400 patients were included, of which 138 received 4xddAC- 4xTHP, 102 – 4xACq3w-4 x THP, 160 – 6xTCHP. The pCR rate in the whole ddAC-THP group was 55,8%. The majority of patients (77,5%) had stage III disease. After propensity matching analysis to adjust for selection bias 102 patients in each A-containing group were included in the final analysis. The pCR rate was 50% in the ddAC group vs 48% in the ACq3w group (p=0.67). Subgroup analysis, including T, N stage, age, ER status, G, ki67 revealed no advantage of ddAC regimen. Next, both A-groups were merged and after propensity matching analysis 143 patients were included both in A- and TCHP-group. The pCR rate was 53,8% in the A-group vs 60,1% in the TCHP group (p=0.34). Subset analysis demonstrated no benefit of A-regimen across subgroups. Conclusion: Our preliminary results suggest that A-containing and TCHP regimens appear to be equivalent in terms of pCR. In case of choosing AC-THP for NA chemo there’s no need to perform the AC arm in dd way since it does not improve efficacy. Citation Format: Elena Kovalenko, Yaroslav Zhulikov, Maxim Khoroshilov, Igor Vorotnikov, Alexander Petrovskiy, Elena Artamonova. Efficacy of dose-dense and anthracycline-free regimens in neoadjuvant chemotherapy of HER2-positive breast cancer: a single-center matched-cohort study. Preliminary results [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-03.

Введение. В последние десятилетия отмечается неуклонный рост заболеваемости раком молочной железы (РМЖ). Несмотря на увеличение выявления РМЖ на ранних стадиях, по-прежнему значительная часть впервые выявленных случаев носят местно-распространенный характер. Подходы к лечению таких стадий претерпевали серьезные изменения, в результате которых общепринятым стандартом был признан комплексный (тримодальный) подход, включающий применение на первом этапе неоадъювантной лекарственной терапии и локальных методов (хирургическое лечение, лучевая терапия) на втором. При этом, несмотря на постоянно увеличивающийся объем знаний об эффективности и безопасности хирургических вмешательств, нерешенными остаются многие аспекты. В частности, открытым остается вопрос влияния сроков выполнения хирургического лечения на вероятность полной патоморфологической регрессии опухоли, а также отдаленные результаты лечения пациенток. Цель. Выработать оптимальный подход к определению сроков выполнения хирургического этапа лечения после завершения неоадъювантной химиотерапии у пациенток с местно-распространенным раком молочной железы. Материалы и методы. В данной̆ работе представлен ретроспективный сравнительный анализ данных пациентов с местно-распространенным РМЖ со стадией опухолевого процесса IIIA-IIIC, проходивших обследование и лечение в НИИ клинической онкологии ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России в период с 2000 по 2020 гг. На первом этапе всем больным была проведена неоадъювантная химиотерапия и/или эндокринотерапия, далее — хирургическое лечение. В работе описано влияние сроков хирургического лечения на частоту полной патоморфологической регрессии опухоли у пациенток с различными подтипами РМЖ; а также на безрецидивную выживаемость и частоту развития хирургических осложнений. Результаты. По результатам проведенного многофакторного анализа было показано независимое негативное влияние временного интервала (> 42 дней) до проведения хирургического лечения на вероятность констатации полной патоморфологической регрессии опухоли (р = 0,049). Факт позднего проведения хирургического вмешательства также снижает показатели безрецидивной выживаемости пациенток, в первую очередь, при высокоагрессивных опухолях молочной железы (тройной негативный, люминальный и нелюминальный HER2-позитивный варианты, р = 0,026). Кроме того, выявлено, что выполнение хирургических вмешательств в ранние сроки (до 21 дня) после завершения неоадъювантной химиотерапии ассоциируется с достоверным повышением рисков хирургических осложнений (14,5 %, р = 0,009). Заключение. Результаты нашего исследования позволили определить оптимальные сроки выполнения хирургического вмешательства у больных местно-распространенным РМЖ.

At present, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors such as palbociclib, ribociclib, and abemaciclib are widely used for the first-line treatment of locally advanced or metastatic breast cancer. However, direct comparisons of these treatment options in randomized studies have not been conducted.Aim of the work is to gather and analyze published data on the comparative effectiveness of CDK4/6 inhibitors in combination with aromatase inhibitors in postmenopausal patients with HR+/HER2– locally advanced or metastatic breast cancer. A systematic review of publications presenting results from original studies on the impact of CDK4/6 inhibitor therapy in combination with aromatase inhibitors on the survival of patients was performed. Nineteen studies with original data on progression-free survival and overall survival were identified. None of the studies found significant differences between different CDK4/6 inhibitors and aromatase inhibitors in terms of progression-free survival. A statistically significant superiority of ribociclib over palbociclib in terms of overall survival was observed in a single matching-adjusted indirect comparison, while seven other studies of various types (real-world data studies, matching-adjusted indirect comparisons, and meta-analyses) did not find significant differences between the investigated drugs in terms of overall survival.Currently, there is no compelling evidence of the superiority of one CDK4/6 inhibitor over others. The decision on the preference for a specific drug within the class can only be made after conducting direct randomized comparison trials, or accumulating sufficient real-world data on the use of palbociclib, ribociclib, and abemaciclib.

Abstract Introduction: Dose-dense adjuvant CT improves long-term outcomes, which has been proved in clinical trials and meta-analysis. However, the efficiency of thе modern dose dence (dd) anthracycline-taxane (A-T) sequential regimens in the neoadjuvant (NA) setting of ER+HER2- breast cancer (BC) has not been assessed. Tumour-infiltrating lymphocytes (TILs) play a key role in the formation of anti-tumor immunity and can be one of the markers of treatment efficacy and prognosis. Studies evaluating TILs in ER+ BC have mixed results. Materials and methods. The aim of the study was to assess the rate of RCB 0-I of 4xddAC (doxorubicine/cyclophosphamide)–T (4xdocetaxel once every 3 weeks or 12xpaclitaxel weekly) NA chemo compared to standart regimen and to study the subpopulation composition of the lymphoid infiltrate and its effect on achieving RCB 0-I. RCB 0-I as a primary end point was chosen due comparable long-term results in ER+HER2- BC as per meta-analisys. Results: The study included pts with stage II-III ER+(ER≥10%) HER2- BC who received NA A-T chemo in a single center from Jan 2017 to Aug 2022. The majority of patients (85,2%) had stage III disease. Statistical hypothesis: NA ddAC–T chemo would increase the rate of RCB 0-1 to 32% from 22% with ACq3w (once every 3 weeks)-T, with a study power of 80%, ά = 0.05, 138 patients should be included in the study. A total of 315 patients were included, 147 received ddAC-T and 168 - ACq3w-T. After propensity matching analysis 138 patients in each group were included in the final analysis. TILs were studied in core-biopsy samples before NA chemo in 79 patients by flow cytometry. The following 8 subpopulations of lymphocytes were assessed as percentage in the cell pool: CD3+, CD3+CD4+, CD3+CD8+, CD4+CD127+CD25+, CD3-CD19+, CD3-CD16+CD56+, CD3+CD16+CD5+, CD8+CD279+(PD-1). The results are presented in medians (Me) due to abnormal distribution. The RCB 0 rate was 18.8% in the ddAC-T group vs 14.5% in the ACq3w-T group (p=0.379), RCB 0-1 - 33.3% vs 21.7% respectively (p=0.04). According to subgroup analysis, significant benefit of ddAC regimen found in patients ≤ 50 y.o., cN0, with PR ≥20%. For the following populations of TILs significant differences in Me for RCB0-I vs RCB II-III were observed: CD3+CD8+, CD3–CD19+, CD3–CD19+, CD8+CD279+. In multivariative analisys CD8+CD279+(PD-1)≤Me proved to be an independent predictive factor for RCB 0-I (p=0,048). Immunological signature CD8+CD279+ ≤ Me, CD3+CD8+ ≤ Me, CD4+CD25+ > Me, CD3-CD19+ > Me was associated with the rate of 66,7% of RCB 0-I vs 0% with the signature with the opposite values. Conclusion: ddAC-T NA chemo compared to standart regimen in ER+HER2- BC increases RCB0-1 rate. CD8+CD279+(PD-1)≤Me is an independent predictive factor for RCB 0-I. Citation Format: Elena Kovalenko, Elena Artamonova, Yaroslav Zhulikov, Maxim Khoroshilov, Alexander Petrovskiy, Igor Vorotnikov, Tatiana Zabotina, Zaira Kadagidze. Efficacy of neoadjuvant dose-dense versus standard chemotherapy regimens in ER+ HER2-negative breast cancer: a single-center matched-cohort study. Exploratory analysis of immune markers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-12.

Introduction. Neoadjuvant chemotherapy (NACT) is the standard of care for II–III stages of TN BC. Complete pathomorphological response (pCR) is associated with a signifiant increase in event-free and overall survival. In addition, in the absence of pCR, post-neoadjuvant adjuvant therapy is prescribed, while if pCR is achieved, additional treatment is not carried out. Despite a large number of studies on NACT of TN BC, different NACT regimens in various clinical trials make it diffiult to interpret their results.Objective. To investigate the effiacy of 4ddAC followed by 12 weekly cycles of paclitaxel and carboplatin in TN BC (according to the RCB system and the frequency of pCR); determine the predictive factors for the effectiveness of this chemotherapy regimen, and the effect of dose intensity on the pCR rate.Methods. This prospective study included 154 patients with TN breast cancer who received dose-dence neoadjuvant chemotherapy from January 2017 to March 2022.Results. PCR rate was 53.25 % (n = 82), RCB 0–I was 66.88 % (n = 103), disease progression was observed in 3.25 % (n = 4). The frequency of germline mutations in the BRCA1/2 genes was 21.43 % (n = 33). The most common mutation was BRCA1 5382insC – 63.64 % (n = 21) of all BRCA1/2 mutations. Rare mutations detected by NGS accounted for 30.3 % (n = 10). The only factor associated with a signifiant increase in the pCR rate was age ≤50 years (p = 0.010), there was a trend towards an increase pCR rate in the subgroups T1–2 (p = 0.052) and BRCA1/2 mut (p = 0.080). There was no effect of the dose intensity on the achievement of pCR.Conclusions. This retrospective analysis is the largest study evaluating the effiacy of 4 ddAC followed by 12 PC in NACT TN BC. The regimen allows to achieve a high frequency of pCR, despite the large proportion of patients with locally advanced breast cancer. The high frequency of rare mutations in the BRCA1/2 genes and the potential therapeutic signifiance of this marker in residual disease treatment dictates the need for NGS in all patients with TN in breast cancer.

Introduction. The efficacy of dose-dense AC in adjuvant chemotherapy of luminal breast cancer (ER+ BC) compared with the standard dosing regimen followed by switching to taxanes has been proven in numerous clinical trials and in a large meta-analysis of the EBCTCG group. However, no study about efficiency of this regimen in neoadjuvant setting has been published. The aim of the study. To assess the effectiveness of dose-dense regimens of neoadjuvant chemotherapy (NAC) of ER + HER2-BC (4 AC once every 2 weeks (dose dense, ddAC), then 4 courses of Docetaxel once every 3 weeks or 12 weekly injections of Paclitaxel [4D/12P]) and their comparison with the standard ones (AC once every 3 weeks [ACq3w], hereinafter 4D/12P). Primary end points are complete response rate (pCR) and RCB0–I. Methods. This retrospective study included patients with resectable or locally advanced luminal HER2-negative breast cancer who received NAC from Janu 2017 to Aug 2022. Statistical hypothesis – the dose-dense regimen AC increases the frequency of RCB0–I from 22 to 32% compared to the standard dosing regimen with subsequent switching to taxanes, with a study power of 80%, ά = 0.05, 138 patients should be included in the study. A total of 315 patients were included in the study, of which 147 and 168 patients received dose-dense (ddAC) and standard chemotherapy (ACq3w), respectively. After propensity matching analysis 138 patients in each group were included in the final analysis. Results. The pCR rate was 18.84% in the ddAC group versus 14.49% in the AC q3w group, the differences were not statistically significant (p = 0.379). The frequency of RCB0–I was higher in the ddAC – group 33.33% versus 21.74% in the AC q3w (p = 0.040). According to the subgroup analysis, rate of RCB0–I was significantly higher in patients younger 50 years, cN0, with the expression of progesterone receptors in ≥ 20%. Conclusions. This is the first study to compare the efficacy of a ddAC NAC with a standard regimen for ER + HER2-BC. NAC with ddAC is associated with an increase in RCB0–I rate.

The heterogeneity of breast cancer (BC), which determines various clinical scenarios of the disease, is still inaccessible to our understanding. Heterogeneity is based primarily on intrinsic subtypes of breast cancer, determined using genomic tests. Currently, four intrinsic subtypes are generally recognized: luminal A and B, HER-enriched (HER2-E) and basal-like. HER2-E subtype in luminal HER-negative (ER+HER–) breast cancer accounts for 11–22 per cent of cases. The efficacy of a combination of hormone therapy (HT) and the CDK4/6 inhibitor ribociclib in the HER2-E subtype was evaluated in a large exploratory analysis of MONALEESA-2, -3, and -7 trials. The gain in progression-free survival (PFS) and overall survival (OS) from the addition of ribociclib to HT was observed in all intrinsic subtypes, except for basal-like, and reached maximum in HER2-E subtype: Ribociclib increased the median PFS to 16.4 months from 5.5 months on HT (HR = 0.389; p < 0.0001) and median OS to 40.3 months from 29.4 months (HR = 0.600; p = 0.0180). The significant frequency of occurrence of the HER2-E subtype in ER+HER-BC, the low efficiency of monoHT in this subtype is another argument in favor of prescribing combination therapy in early lines. Information about the intrinsic subtype not only brings us closer to understanding tumor heterogeneity, but may also become a significant factor in determining treatment tactics in the future.

Recent studies have shown that triple-negative breast cancer (TN BC) is characterized by the highest mutational load and immunogenicity compared to other subtypes, as well as the degree of tumor-infiltrating lymphocytes (TILs) infiltration, which play an important role in the development of antitumor immunity and treatment response. A significant disadvantage of the standard immunohistochemical method for determining TILs is the inability to fully assess the subpopulation structure of the immune infiltration, including minor populations.Aim: The evaluation of the subpopulations of breast cancer lymphoid infiltration in patients receiving neoadjuvant chemotherapy (NACT) and its influence on achieving a complete pathomorphological response (pCR = RCB 0).Materials and methods: The study included 90 patients who received NACT in following regimen: AC (doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 ) every 2 weeks, followed by 12 weekly infusions of paclitaxel 80 mg/m2 + carboplatin AUC2. The TILs subpopulations were evaluated in core-biopsy samples prior to the NACT in all patients. The analysis performed by flow cytofluorimetry. Clinical and immunological analysis was performed for the following 9 lymphocyte subpopulations: CD3+CD4+, CD3+CD8+, CD4+CD25highCD127– / low, CD3–CD19+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD4+CD25+, CD8+CD279+, CD4+CD279+.Results: The frequency of pCR was 51,1 %. The total TILs content in groups with pCR and non-pCR (RCB 0 vs RCB I–III) did not differ statistically (p = 0.271). The subpopulations analysis for CD3+CD8+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD3+CD4+, CD3–CD19+, CD4+CD25+, CD4+CD25highCD127– / low and CD4+CD279+ revealed no statistically significant differences between the median values in the groups with pCR and non-pCR. A study of the CD8+CD279+ population showed a higher level of these cells in patients achieved pCR / RCB 0 (median 18,6 % vs 12,3 % with RCB I–III) (p = 0.033). With CD8+CD279+ above the median (high, > Me), the pCR frequency was 61 % vs 35 % in the subgroup with CD8+CD279+ less than or equal to the median (low, ≤Me). Despite the absence of statistically significant differences in the content of CD3+CD16+CD56+(NKT-cells) in groups with pCR and non-pCR (p = 0.091), numerical differences in medians were revealed: 9,9 % and 8,3 %, respectively. At the same time, with CD3+CD16+CD56+(NKT) > Me (high), the pCR frequency was 63 % vs 36 % in the subgroup with CD3+CD16+CD56 + ≤Me (low). When selecting a narrow subgroup (CD8+CD279+ high and CD3+CD16+CD56+ high), the frequency of pCR was 87,5 % vs 27,3 % in the group with both low indicators.Conclusion: The high content of CD8+CD279+ and CD3+CD16+CD56+ in the tumor sample before the treatment start was a predictor of high sensitivity to NACT and is associated with a higher frequency of pCR.

Triple-negative breast cancer has no specific treatment and unfavorable prognosis. Eribulin is one of the drugs widely used in this cohort of patients. In addition to its antimitotic effect, eribulin has an immunomodulant effect on the tumor microenvironment. In this study, we discover immunological markers, such as tumor-infiltrating lymphocytes, CD8+, CD4+, FoxP3+, CD20+ lymphocytes, and their PD1 positivity or negativity, with the ability to predict benefits from eribulin within locally advanced or metastatic triple-negative breast cancer. The primary objective was to explore the association of composition of immune cells in the microenvironment with response to eribulin. The key secondary objective was overall survival. Seven-color multiplex immunofluorescence was used to phenotype lymphocytes in the primary tumor. It has been shown that the PD1-negative-to-PD1-positive B cells ratio in primary tumors more than 3 is an independent predictor of the short-term effectiveness of eribulin [OR (95%CI) 14.09 (1.29-153.35), p=0.0029] and worse overall survival [HR (95%CI) 11.25 (1.37-70.25), p=0.0009] in patients with locally advanced or metastatic triple-negative breast cancer.

Background. Triple negative breast cancer has no specific treatment sites for chemotherapy and is unfavorable in terms of prognosis. One of the drugs widely used in this cohort of patients is eribulin, which in addition to its antimitotic effect has an effect on the tumor microenvironment. The search for biological criteria that will allow predicting the effectiveness of the drug is assumed relevant since it will help to select patients who may receive the most benefit from certain therapy regimens.Objective: identification of immunological predictors of the therapeutic effectiveness of eribulin in patients with locally advanced or metastatic triple-negative breast cancer.Materials and methods. The study included 20 patients with locally advanced and metastatic triple negative breast cancer. 50 % had a short-term response (progression-free survival <3 months) to eribulin therapy, and 50 % had a long-term response (progression-free survival >6 months). Seven-color immunofluorescence was used to determine the subpopulation composition of tumor-infiltrating lymphocytes and their PD1 expression. Image acquisition and analysis were performed using the Vectra® 3.0 system and InForm® software (Akoya Biosciences, USA).Results. It has been shown that the ratio of the number of PD1-negative to PD1-positive CD20+ B-lymphocytes less than 5.5 associated with the long-term effectiveness of eribulin in patients with locally advanced or metastatic triple negative breast cancer.Conclusion. The results showed that the ratio of the number of PD1-negative to PD1-positive CD20+ B-lymphocytes can be considered as a possible marker to predict the effectiveness of eribulin in patients with breast cancer.

Background. Combination of gemcitabine, metronomic capecitabine and mitotane (GemCap + m) is the most studied regimen in second and subsequent lines of therapy for advanced adrenocortical cancer (ACC). Previously published studies do not give a definitive answer to the question- what plays a key role in realizing the response to treatment: chemotherapy or mitotane in therapeutic concentration. Aim. Evaluation the efficacy and safety of GemCap + m combination with the standard dosing regimen of capecitabine in patients with metastatic ACC. Materials and methods. This retrospective single-center clinical study included patients over 18 years of age with histologically confirmed ACC with disease progression after completion of platinum-containing therapy. They received chemotherapy regimen gemcitabine 800 mg/m 2 for days 1, 8 and capecitabine 1000 mg/m 2 orally 2 times at days 1–14 of the 21-day cycle with mitotane. we evaluated objective response, stabilization of disease, 6-months disease control rate and median progression-free and overall survival. Radiological assessment according to RECIST 1.1 criteria was carried out every 6–8 weeks of treatment. Results. The study included 25 patients. mitotane concentration above 14 ng/mL was achieved in 22 (88 %) patients, of which 21 (84 %) reached therapeutic concentration in previous treatment lines. 80 % of patients received treatment as 2 nd line, 20 % as 3 rd and subsequent lines. The objective responses and disease stabilization was observed in 1 (4 %) and 11 (44 %) of patients, respectively. Disease control for at least 6 months rate was 24 %. median progression-free and overall survival were 3.2 months and 12.17 months, respectively. Toxicity grade 3–4 was observed in 28 % of patients. gemcitabine dose reductions due to thrombocytopenia grade 1–2 were required in 2 cases (8 %), no capecitabine reductions were necessary. Conclusion. This study demonstrates the effectiveness of a new dose regimen of chemotherapy GemCap + m in the second and subsequent lines of therapy for metastatic ACC. The progression of the disease against the background of previous lines of therapy at a therapeutic concentration of mitotane in the majority of patients indicates the effectiveness of the chemotherapeutic component of gemCap in a cohort of patients resistant to platinum and mitotane.

Adrenocortical cancer is an orphan tumor with poor prognosis. The combination of EDP chemotherapy regimen and mitotane is the standard for the first‑line therapy. But there are no effective options for the second and consequent lines of therapy. The standard of second‑line therapy is the combination of gemcitabine, capecitabine and mitotane, which provides an objective response in 4–7 % of patients. Achievement of the therapeutic concentration of mitotane is the most important predictive factor of efficiency of GemCap + mitotane regimen, and, therefore, it is recommended to continue mitotane therapy after progression to mitotane. Recently, many researches regarding the efficiency of targeted and immunotherapy of adrenocortical cancer have been published. However, there are no standards for the third and subsequent lines of treatment. This review outlines the current views and perspectives of systemic therapy for advanced and metastatic adrenocortical cancer.