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For patients with the metastatic subtype of luminal HER-2-negative (HR+/HER2-) breast cancer (mBC) in the absence of visceral crisis, the gold standard of treatment is a combination of CDK4/6 inhibitors and aromatase inhibitors, regardless of their menopausal status and the sites of metastasis. The effectiveness of this approach was confirmed in the MONARCH, PALOMA, MONALEESA study cycles for the drugs abemaciclib, palbociclib and ribociclib, respectively. Metastasis in the central nervous system (CNS) in breast cancer complicates the treatment of patients and leads to the search for new approaches to the choice of therapy. To date, neurosurgical and radiosurgical techniques are actively used, however, drug therapy still stands for the leading positions. Data on the use of CDK4/6 inhibitors or aromatase inhibitors in patients with CNS metastases are limited. Most studies did not include patients with CNS metastases, only PALOMA-2,3 and MONALEESA-3 studies allowed the inclusion of patients with either “inactive” CNS metastases or after exposure to local treatment methods (for example, radiosurgery, radiotherapy, or surgery). In the study of real clinical practice of combined endocrine therapy with ribociclib (CompLEEment-1) allowed the inclusion of patients with active brain metastases (n = 51), while the subgroup analysis demonstrated the benefits of using a combination of ribociclib and aromatase inhibitors in patients in this difficult clinical situation. In the article, the authors review the available data from randomized clinical trials and real clinical practice, and also illustrate with their own observation.

Introduction. Probability of development of multiple primary tumors in patients who received treatment due to head and neck cancers varies between 5.6 and 35.9 % per different sources. moreover, treatment capabilities are severely limited by postoperative anatomical changes and previous radiation therapy, and the second tumor frequently causes death in these patients.The study objective is to identify the epidemiological features of the development of synchronous and metachronous primary multiple tumors in the head and neck.Materials and methods. The article analyzes data on 103 patients with multiple primary tumors who received treatment due to tumors of the head and neck between 1991 and 2020 at the N.N. Blokhin National medical Research Center of Oncology and A.S. Loginov Moscow Clinical Scientific Center.Results. During the study, typical locations of metachronous tumors in patients who received treatment due to primary malignant tumors of the head and neck were determined, duration of development of multiple primary tumors, treatment methods and survival rates were analyzed.Conclusion. Due to high risk of multiple primary tumors in patients who received treatment due to malignant tumors of the head and neck in the next 5 plus years, it is expedient to observe these patients during their whole lifetime. Considering typical locations of metachronous tumors, examination during dynamic observation should include instrumental methods such as panendoscopy. Surgical treatment should involve the whole spectrum of minimally invasive interventions including CO2 laser surgery and transoral robot-assisted interventions.

Over the past two decades, the surgical treatment of breast cancer (BC) has changed from standard radical mastectomies to organ-preserving and reconstructive plastic surgeries using endovideosurgical and robotic technologies. Robot-assisted radical subcutaneous mastectomy, as a minimally invasive method of surgical treatment of BC in the early stages, is recognized as safe and effective.The results of robot-assisted radical subcutaneous mastectomy and radical subcutaneous mastectomy with endoprosthesis in 27 patients with histologically verified BC are presented. A comparative assessment of postoperative complications of robot-assisted radical subcutaneous mastectomy with endoprosthesis and radical subcutaneous mastectomy with endoprosthesis was performed. It was found that the postoperative period in robotic interventions is more favorable, which confirms the low need for analgesics, the absence of signs of the formation of hematomas of the surgical wound, as well as a decrease in the frequency of inflammatory infiltrates and gray soft tissues in the area of the postoperative suture. Performing a robot-assisted radical subcutaneous mastectomy with endoprosthesis can significantly improve the surgical and aesthetic results of BC treatment in the early stages of this disease.

Introduction. Сombination of alpelisib plus fulvestrant is approved in patients with hormone receptor positive, HER2-negative, PIK3CA-mutated advanced breast cancer (ABC) after progression on hormonotherapy. Efficacy data of alpelisib in heavily pretreated patients with HR+/HER-2-, PIK3CA-mutated advanced breast cancer are limited, only results from phase I trial are available. Here we report our results of alpelisib efficacy in 19 heavily pretreated patients.Object: to evaluate efficacy and safety of combination alpelisib plus fulvestrant in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer in initial and later lines of therapy in real clinical practice.Materials and methods. Combination of alpelisib plus fulvestrant was investigated in 19 patients with HR+/HER2-, PIK3CAmutated ABC, alpelisib at a dose of 300 mg per day plus fulvestrant at a dose of 500 mg i.m. every 28 days and once on day 15. Treatment continued until disease progression or unacceptable toxicity.Results. From February 2021 19 patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer were treated with alpelisib plus fulvestrant. The data cut off is October 2021. Median lines of treatment in advanced disease was five, including 19 (100%) patients received CDK4/6, 14 (74%) – fulvestrant and/or everolimus and 15 (79%) – chemotherapy. 4 (21%) received alpelisib in a second line, 15 (79%) – in subsequent lines. Median progression-free survival was 7 months. The response was evaluated in 18 patients: partial response was achieved in 5 (28%) patients, stable disease – in 9 (50%), disease progression – 4 (22%). The most frequent adverse events were hyperglycemia – 74% (grade 3 – 22%), creatinine increased – 42% and rash – 37% (grade 3 – 22%). Only one patient has discontinued the treatment due to Quincke`s edema.Conclusions. Combination of alpelisib with fulvestrant is an effective option both in initial and later lines of therapy in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer including fulvestrant, CDK4/6 inhibitors and/or everolimus – pretreated patients.

Relevance. Data on the efficacy of endocrine and chemotherapy regimens in patients with hormone-resistant metastatic breast cancer (mBC) after progression with CDK4/6 inhibitors are limited; the search for an effective therapy regimen in this clinical situation is an urgent task of clinical oncology. Aim. Evaluate the efficacy and safety of eribulin therapy in patients with HR+/HER2- mBC after progression with CDK4/6 inhibitors; compare the results of the Russian study and the EMPOWER observational study in the USA. Materials and methods. The Russian observational study included 54 patients (pts) with HR+/HER2- mBC, who were treated with eribulin after CDK4/6 inhibitors in 24 Russian Cancer hospitals. The median age of pts was 56 years; 75.9% of them had recurrent BC, 24.1% de novo BC stage IV; 51.9% of pts had progression with CDK4/6 inhibitors in the first 6 months of therapy (primary endocrine resistance); 48.1% of patients had progression in the period from 6 to 38 months; 89.1% had visceral site of metastases (liver MTS 65.5%, lung MTS 52.8%, brain MTS in 7.5%). Eribulin was used after anthracyclines and taxanes in 94.4% of cases. The efficacy and safety of eribulin therapy in patients with HR+/HER2- mBC after progression with CDK4/6 inhibitors was studied, as well as subgroup analysis according to age, sites of metastasis, and previously treatment options. Results. Eribulin was prescribed in the standard regimen of 1.4 mg/m2 on days 1 and 8, the interval between cycles was 21 days, the number cyclys of chemotherapy was 144 (median 8, the mean number of cycles 10.5). With a median follow-up of 11.5 months (from 3 to 36 months), 30 patients (55.6%) continue therapy with eribulin at present; therapy was cancelled in 24 patients due to progression in 22 (40.7%) cases, and due to intolerable toxicity in 2 (3.7%) patients. The maximum response to eribulin therapy included partial response (in 11 cases, 24.4%), stable disease (in 30 cases, 66.7%) and progression in 4 (8.9%) patients. Median PFS with eribulin therapy was 10.0 months; the 6-month, 1-year, and 2-year PFS were 79.5%, 44.8% and 26.5%, respectively. Eribulin therapy was equally effective in different subgroups (p0.05) and did not depend on the age of patients, the previously received treatment, the presence of visceral MTS and liver damage. The best response to chemotherapy with eribulin was observed in lung metastases: median PFS 24 months vs 9.1 months, p=0.056. The safety profile was favorable; adverse events were registered in 34.5% of patients, which required dose adjustment in 18.5% of cases. With a median follow-up of 11.5 months, 92.6% of patients remain alive. Conclusion. Eribulin has demonstrated high efficacy and favorable safety profile in hormone-resistant HER2- mBC in patients with progression when receiving CDK4/6 inhibitor.

Background: CompLEEment-1 (NCT02941926) is an ongoing Phase IIIb trial of ribociclib (RIB) in combination with letrozole (LET) in the first-line setting for patients (pts) with HR+, HER2- ABC, reflecting a real-world clinical setting by including a more diverse pt population than those included in the pivotal MONALEESA trials. Here we report further analyses of the primary endpoint of safety from the completed Core Phase of the trial. Methods: CompLEEment-1 included women of any menopausal status and men with HR+, HER2- ABC treated with ≤1 line of prior chemotherapy and no prior hormonal therapy for advanced disease. Pts received RIB (600 mg QD, 3 weeks on/1 week off) in combination with LET (2.5 mg QD, continuous). Premenopausal women and men received a luteinizing hormone-releasing hormone agonist (3.6 mg goserelin or 7.5 mg leuprolide, Q28D). The primary endpoints were safety and tolerability. Updated analyses included dose reduction/interruption or treatment discontinuation due to adverse events (AEs), clinical impact of AEs of special interest (AESI), and exposure-adjusted incidence/occurrence rates (IRs) for AESI. Results: At data cutoff (November 8, 2019) 3,246 pts had been evaluated (median follow-up of 25.4 months), and median duration of exposure to RIB was 17.5 months; 1,301 (40.1%) pts completed Core Phase treatment, 415 of whom moved to the Extension Phase. Overall, 1,945 (59.9%) pts permanently discontinued treatment, mostly due to progressive disease (34.2%) and AEs (15.5%). Treatment-related AEs were reported in 3,091 (95.2%) pts, leading to dose modification in 2,235 (68.9%) pts. Dose modification occurred most often in pts with grade ≥3 neutropenia (dose interruption, 1,671 [51.5%] pts; dose reduction, 480 [14.8%] pts); treatment discontinuation occurred most frequently in pts with grade ≥3 increased alanine aminotransferase (ALT; 116 [3.6%] pts) or aspartate aminotransferase (AST; 68 [2.1%] pts). Grade ≥3 neutropenia occurred in 1,856 (57.2%) pts, with the median time to first occurrence of 4.1 weeks and median duration of first occurrence of 1.1 weeks. As measured by laboratory values, grade ≥2 increased ALT and AST occurred in 453 (14.0%) and 380 (11.7%) pts, respectively. Grade ≥2 QTcF prolongation was infrequent, occurring in 101 (3.1%) pts, leading 8 (0.2%) pts to discontinue from treatment. AESI rarely led to hospitalization (0 to 0.3%) and none were fatal. Exposure-adjusted IRs for AESI per 100 patient-years of exposure show that with increasing RIB exposure, the IR and the event rates for AESI decreased by a factor of ×2 to ×8 from 0-1 years compared with 1-2 years (Table 1). Conclusions: AEs associated with RIB + LET combination therapy were manageable, consistent with previous Phase III trials of RIB + LET - and adjusted IRs for AESI notably decreased from Year 1 to Year 2 of treatment. These data further support the use of RIB + LET for first-line treatment of HR+, HER2- ABC in both men and women of any menopausal status and in a broader and more diverse patient population. Table 1. Exposure-adjusted IRs for selected AESI per 100 patient-years of exposure0-1 years1-2 yearsAESIIR per 100 PTYaEvents per 100 PTYbIR per 100 PTYaEvents per 100 PTYbNeutropenia276.76410.2292.43200.83ALT increased20.3741.663.796.32AST increased17.5133.272.944.61QTcF prolongation8.4410.221.081.26aIR per 100 PTY: n/100 PTY, number of patients with an event divided by the corresponding sum of the exposure duration for patients, where duration of exposure in patient treatment-years (PTY) is counted up to the first qualifying event (or duration of exposure in time interval for patients without an event).bEvents per 100 PTY: n/100 PTY, number of events divided by the corresponding sum of the exposure duration, where duration of exposure in patient treatment-years (PTY) is duration of exposure in time interval. Citation Format: Janice Lu, Paul Cottu, Miguel Martín, Claudio Zamagni, Aleix Prat, Stephen Chia, Guy Jerusalem, Senthil Rajappa, Constanta Timcheva, Lyudmila Zhukova, Katie Zhou, Jiwen Wu, Lakshmi Menon-Singh, Michelino De Laurentiis. Ribociclib + letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) advanced breast cancer (ABC): Expanded safety analysis of the phase IIIb CompLEEment-1 trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-05.

The editorial touches upon the problem of the possible impact of COVID-19 on CKD patients, mediated by the forced reorganization of the health care system in a whole, the redistribution of its resources in the context of the COVID-19 pandemic. Lack of regular outpatient monitoring, delayed diagnosis and therapy in patients with kidney dysfunction are factors of adverse clinical outcomes - accelerated disease progression, ESKD development and the need for KRT, life-threatening complications, reduced quality of life and survival. The data of a pooled analysis of the impact of the pandemic on specialized renal care and its availability in a number of regions of the Northwest Federal District of Russia and the Moscow Region are presented: a fall in hospital admissions, outpatient consultations and a decrease in the use of hospital beds (on average, by 37 %, 40 % and 32 %, respectively). Principles and conditions of the functioning of health systems associated in the COVID-19 pandemic have been discussed. The main approaches to maintaining the standard level of renal patients care have been formulated, aimed at preventing an unfavorable patient-oriented CKD outcomes. © 2021 Patristica et Mediaevalia. All rights reserved.

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.

Background. We previously found that a decrease in the number of NKT cells and activated CD 25+ peripheral blood lymphocytes (PBLs) before neoadjuvant chemotherapy was associated with an increased likelihood of disease progression in patients with locally advanced triple-negative breast cancer (TN BC).The purpose of this study was to determine the relationship between the initial number of NKT-and CD 25+ PBLs and relapsefree survival (RFS)/overall survival (OS ) in patients with TN BC who received neoadjuvant chemotherapy with cisplatin and paclitaxel followed by surgery.Material and Methods. The study included patients with stage II and III TN BC. The follow-up time was 36 and 66.9 months. Immediately before chemotherapy, the percentage of CD 3+CD 16+CD 56+ (NKT) -, CD 25+- and CD 8+ PBLs was determined by flow cytometry. Statistical analysis of the data was carried out using the Statistics 7 software package. The Kaplan-Meier method was used to determine the relationship between immunological parameters and RFS/ OS .Results. The decreased level of NKT cells before treatment was associated with a decrease in the 3-year RFS [Me: 20.1 (0.533 and 39.7) months] compared to that observed in patients with higher percentage of these cells than in the control (Me was not achieved). There were no statistically significant differences in the 3-year OS between the groups. The initially reduced number of CD 25+ lymphocytes in comparison with the control was associated with decreased rates of both RFS and OS . The difference in DFS and OS was more significant between the groups of patients who simultaneously had an increased initial number of both NKT and CD 25+ cells and patients in whom both cell populations were below normal levels.Conclusion. The initial (prior to chemotherapy) number of NKT and activated CD 25+ PBLs can apparently be a predictive factor in TN BC patients, who received neoadjuvant chemotherapy with cisplatin and paclitaxel.

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 Conclusions. Our data suggest that studied regimen could be an option for patients with stage II–III TN BC. The assessment of the predictive and prognostic factors will help improve the treatment results for patients with stage II–III TN BC.

The use of CDK4/6 inhibitors in combination with endocrine therapy (aromatase inhibitors and fulvestrant) allowed us to radically change our understanding of opportunities in the treatment of hormone-positive HER2-negative advanced breast cancer and determine optimal therapy sequencing. The results of randomized clinical trials and over 5-years accumulated international experience in the use of CDK4/6 inhibitors in real clinical practice prove that the use of combinations with CDK4/6 inhibitors can achieve significant efficacy results and increase the survival rates when prescribed in 1 and 2 lines of treatment.In this paper, we present the results of a survey conducted in July–October 2019 among 48 oncologists in Moscow, that were asked to choose, in their opinion, the most preferable patient’s profile and molecular and biological features of hormone-positive HER2-negative advanced breast cancer, in which the use of combination therapy with CDK4/6 inhibitors will provide the greatest benefit.Conflict of interest. MD M.A. Mukhina is the medical director of oncology in the Eurasia and Baltic region of Pfizer Innovations Company

Background. Triple negative breast cancer (TNBC) is the most aggressive molecular subtype. It is mostly observed in younger patients, however, substantial proportion of patients are above age of 60. Despite that, this group of patients was not studied and analyzed separately in previous studies. Objectives. To establish efficacy of neoadjuvant chemotherapy in elderly patients with stage II-III TNBC and patterns of progression for this group of patients. Methods. Since 2014 we treated 92 patients with histologically confirmed stage II-III TNBC. Neoadjuvant therapy included 6 cycles of Cisplatin 75mg/m2 day 1 and Paclitaxel 80mg/m2 days 1, 8, 15, every 4 weeks according to local protocol. After neoadjuvant chemotherapy patients proceeded to radical breast surgery with assessing pathological response. Then we analyzed clinical characteristics of patients and their survival according to the pathological response achieved. Results. In our analysis were included 92 patients, 22 of them were elderly patients (above 60). Pathological complete response was achieved in 57,6% of all patients. In the elderly group we observed significantly higher proportion of tumors with advanced stages (N3: 40,9% vs 20,0%, p Table 1. Survival outcomes.SurvivalBelow 60 y.o.Above 60 y.o.Recurrence-free survival Conclusion. In our analysis elderly patients with early and locally advanced TNBC demonstrate decreased response, another safety profile and lower survival rates. Different efficacy could be explained with lower number of cycles of neoadjuvant chemotherapy administered and more advanced stages upon presentation. Different metastatic patterns which we observed in younger and elderly patients should be further studied. Citation Format: Olga Gordeeva, Irina Kolyadina, Lyudmila Zhukova, Inna Ganshina, Dmitry Komov, Andrey Meshcheryakov. Patterns of survival and efficacy of chemotherapy in elderly patients with triple-negative breast cancer treated in the neoadjuvant setting [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-34.

Aim. To search early signs of cardiotoxicity in patients receiving anticancer therapy and evaluate the effectiveness of cardioprotection with an angiotensin-converting enzyme inhibitor, beta-blocker and myocardial cytoprotector.Material and methods. The study included 98 patients with high and very high risk of cardiotoxicity according to the Mayo Clinic scale (USA). Cancer patients with hypertension were offered cardioprotective treatment with a fixed-dose combination of perindopril and bisoprolol, and patients with very high risk and concomitant coronary artery disease additionally trimetazidine.The patients were divided into 2 following groups: the experimental group (n=50), where patients were prescribed cardioprotective therapy, and the control group (n=48), which consisted of patients who refused or had contraindications to cardioprotection. All patients underwent an examination, including the collection of complaints and anamnesis, physical examination, electrocardiography and echocardiography with an assessment of left ventricular (LV) global longitudinal strain before chemotherapy and 1, 3, 6, 9 and 12 months after initiation of anticancer therapy.Results. In patients of the control group, by the end of the follow-up, the left atrial volume index and LV end-diastolic volume index significantly increased. In the main group, these indicators did not change significantly. In the control group, by the final visit, the LV ejection fraction significantly decreased in comparison with the initial value and the value in the first group. After 6, 9 and 12 months, there was a significant decrease in the LV global longitudinal strain in the control group, while in the main group this indicator remained within the normal range. The mortality rate in the control group was significantly higher (15% vs 2% in the experimental group). In the experimental group, cardiotoxic complications occurred in 28%, while in the control group — in 78% of patients.Conclusion. The study demonstrated the significant importance of cardiac monitoring and primary drug prevention of cardiotoxicity of anticancer therapy. A sig nificant deterioration in LV systolic function was shown in patients with a high and very high risk of cardiotoxicity who did not receive cardioprotective therapy, while its high efficiency was demonstrated in patients of the experimental group.

Up until recently, neoadjuvant and adjuvant treatment regimens for breast cancer (BC) were considered equivalent in their effect on long-term treatment outcomes. Despite the fact that additional information on the prognosis of patients (achievement or failure to achieve complete drug pathomorphosis) was obtained during neoadjuvant therapy, we could not change this prognosis, since there was no evidence that any variant of adjuvant therapy could improve survival of patients, who did not achieve complete morphological tumour regression. In December 2018, investigators presented the results of the first planned interim analysis of invasive disease-free survival (iDFS) of patients with early HER2-positive breast cancer, who had residual tumour after neoadjuvant anti-HER2-containing therapy, depending on the adjuvant treatment option: either trastuzumab emtansine (n = 743) or trastuzumab (n = 743). The expected 3-year iDFS in patients, who received trastuzumab emtansine as adjuvant therapy, was 88.3%, while that in the standard trastuzumab group accounted for only 77% (RR = 0.50; 95% CI 0.39–0, 64; h

The results of treatment of localized (early) pancreatic cancer are unsatisfactory despite all achievements of modern clinical and surgical oncology. Nevertheless, certain success was achieved even in these extremely unfavorable patients regarding their prognosis. The authors analyzed evolution of adjuvant therapy, as well as new concepts in the treatment of borderline resectable and resectable pancreatic cancer. Modern anticancer therapy with acceptable toxicity profile significantly improved the outcomes. However, further research is needed to improve the effectiveness of treatment despite favorable current results.

Palbociclib is the first-in-class drug of CDK 4/6 inhibitors group. The use of palbociclib in combination with endocrinotherapy (ET) opens up new possibilities for the treatment of metastatic hormone receptor-positive (HRP+) HER2-negative (HER2-) breast cancer (mBC). Palbociclib has gained world attention and is included in all clinical guidelines, both international and domestic, as a new standard of first- and second-line therapy of HRP+ HER2- mBC. The article presents the updated results of PALOMA-2 and PALOMA-3 studies and the results of use of palbociclib in combination with ET in real clinical practice.

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.

Background Coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO on 11 March 2020 and global surgical practice was compromised. This Commission aimed to document and reflect on the changes seen in the surgical environment during the pandemic, by reviewing colleagues’ experiences and published evidence. Methods In late 2020, BJS contacted colleagues across the global surgical community and asked them to describe how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had affected their practice. In addition to this, the Commission undertook a literature review on the impact of COVID-19 on surgery and perioperative care. A thematic analysis was performed to identify the issues most frequently encountered by the correspondents, as well as the solutions and ideas suggested to address them. Results BJS received communications for this Commission from leading clinicians and academics across a variety of surgical specialties in every inhabited continent. The responses from all over the world provided insights into multiple facets of surgical practice from a governmental level to individual clinical practice and training. Conclusion The COVID-19 pandemic has uncovered a variety of problems in healthcare systems, including negative impacts on surgical practice. Global surgical multidisciplinary teams are working collaboratively to address research questions about the future of surgery in the post-COVID-19 era. The COVID-19 pandemic is severely damaging surgical training. The establishment of a multidisciplinary ethics committee should be encouraged at all surgical oncology centres. Innovative leadership and collaboration is vital in the post-COVID-19 era.

Chemotherapy is among the primary methods of treating advanced breast cancer. It was shown that clinical efficacy of various chemotherapeutic agents in many cases depends not only on their direct cytostatic and/or cytotoxic effect upon tumor cells, but also on their ability to modulate phenotype of the tumor cells and to influence anti-tumor immune response. Initial state of the immune system and its response to treatment is crucial. Antitumor response involves cells of innate and adaptive immunity (NK, NKT, T cells). These populations are heterogeneous and contain, e.g., cells with antitumor activity and regulatory (suppressor) cells that suppress immune response and promote tumor progression. The aim of this work was to determine the relationship between the initial state of cellular immunity of patients suffering from locally advanced breast cancer with triple negative phenotype, and clinical effect of chemotherapy (cisplatin + doxorubicin/paclitaxel), and studying effects of the therapy upon subpopulation profiles of peripheral blood lymphocytes in the patients. We registered the terms of the disease progression as well as overall survival and progression-free survival. The disease progressed in 25 of 53 cases (47.2%) whereas 28 of 53 patients (52.8%) remained progression-free. The observation period was 35.5 months. Laboratory examination of the patients included immunophenotyping of peripheral blood lymphocytes and determination of NK cell cytotoxic activity before and after chemotherapy. Percentages of effectors and regulatory lymphocyte populations were determined. The results obtained showed that, for some lymphocyte subsets, the pre-treatment differences of cell percentage deviations from control were found between the progression-free groups and patients with progression of the disease. The differences in percentages of NKT cells and lymphocytes expressing CD25 activation marker proved to be most significant. Decreased number of NKT cells and activated CD25+ lymphocytes prior to chemotherapy was associated with increased probability of disease progression. Reduced percentage of NKT cells against control was observed in 56% of patients from the progression group (PD), and only 21.4% in the group free of disease progression (DF). [OR = 4.6 (95% CI 1.4 to 15.4)]. Percentage of CD25+ lymphocytes was decreased from 68.2% in the PD group, and 28.6% for DF patients [OR = 5.4 (95% CI 1.6-18.1)]. We studied relationships between the overall survival (OS) and percentage of perforin-containing NK, NKT, and T cells, and mean perforin fluorescence density (PFD) in these lymphocyte subsets in 26 of the 53 patients before treatment. A statistically significant positive correlation was revealed between OS and perforin PFD in all the three cell populations under study. Normalization of the parameters altered before treatment, and an increase of T cell numbers was observed in the disease-free patients.

The main method of treatment of local stages of clear cell renal cancer is surgical. The question of conducting adjuvant irradiation and chemotherapy after radical operations is open. Patients with solitary distant metastases and a favorable prognosis may become candidates for surgical treatment. Surgical removal of isolated solitary metastases allows to achieve 35–60 % of 5-year overall survival. The patient, observed in N.N. Blokhin National Medical Research Center of Oncology with metastasis of renal cancer in the pancreas, and then in the breast is an extremely rare clinical case presented in this article.

To evaluate the influence of clinical and morphological factors and HER2 copy numbers on pathologic complete response (pCR) rates in patients with HER2-positive stage II-III breast cancer (BC).Treatment results were studied in 73 patients with HER2-positive Stage II-III BC, who received treatment at the N.N. Blokhin National Medical Research Center of Oncology in 2015 to 2018. Treatment included neoadjuvant chemotherapy (NACT) with HER2-blockade and radical surgery followed by the evaluation of a pathologic response in the primary tumor and regional lymph nodes. The patients` age varied from 29 to 71; its median was 51.5; 45.2% of patients had primary operable stages (TA breast pCR (bpCR) was achieved in 57.4% patients; bpCR and lymph node CR (lnCR) were noted in 48.9% patients. The rates of bpCR significantly depended on female age, chemotherapy regimen, addition of Pertuzumab, and HER2 copy number. That of bpCR in women less than 35 years of age, in those aged 36-50 years, and in those aged older than 50 years was 22.2, 57.7 and 71.9%, respectively (p=0.026). The maximum bpCR rate observed with the TCH±P regimen was 80.0%, that with anthracycline-containing regimes was 52.8% (p=0.045), and the addition of Pertuzumab increased complete response rates up to 88.9% (that with Trastuzumab was 54.2% (p=0.049). The relationship of bpCR rates to the detection of cluster amplification turned out to be highly significant (81% in its detection and 48.9% in its absence (p=0.013). In addition, clustered HER2 amplification was the only significant predictive factor for complete regression in the primary tumor and lymph nodes: in its presence, the tpCR rate reached 68.8% versus 38.7%.Clustered amplification of the HER2 gene is the most significant factor of sensitivity to anti-HER2 therapy for Stage II-III BC, and is associated with the maximum rate of both bpCR and total pCR. Further study of this factor may assist in optimizing the treatment algorithm for HER2 + BC.Оценить влияние клинико-морфологических факторов, а также количества копий гена HER2 на частоту достижения полного патоморфоза (pCR) у больных с HER2+ раком молочной железы (РМЖ) II-III стадии.Изучены результаты лечения 73 больных РМЖ II-III стадии, получивших комплексное лечение в ФГБУ 'НМИЦ онкологии им. Н.Н. Блохина' с 2015 по 2018 г. (неоадъювантная химиотерапия (НАХТ) с анти-HER2-блокадой и радикальное хирургическое лечение с оценкой лечебного патоморфоза первичной опухоли и регионарных лимфатических узлов). Возраст пациенток составил от 29 лет до 71 года, медиана - 51,5 года; 45,2% пациенток имели первично-операбельные стадии (T1-3N0-1) и 54,8% - местно-распространенные. Степень анаплазии G2-G3 была у всех больных, люминальный HER2-положительный РМЖ был диагностирован у 41,1% пациенток, у 58,9% опухоли были гормононегативными; Ki-67 ≥20% имели 91,5% пациенток. Предоперационная системная терапия включала антрациклинсодержащие режимы у 75,3% женщин (4 цикла химиотерапии по схеме АС с переключением на 4 цикла паклитаксела в дозе 175 мг/мПолный регресс опухоли молочной железы (bpCR) отмечен у 57,4%, полный ответ в опухоли молочной железы и в лимфатических узлах (tpCR) - в 48,9% случаев. Частота достижения bpCR значимо зависела от возраста женщин, режима химиотерапии, добавления к лечению пертузумаба и количества копий гена HER2. Частота достижения bpCR у женщин до 35, 36–50 и старше 50 лет составила 22,2, 57,7 и 71,9% соответственно; p=0,026. Максимальная частота bpCR отмечена при применении режима TCH±Р - 80%, при антрациклинсодержащих режимах 52,8%; p=0,045, добавление пертузумаба увеличивало частоту полных ответов до 88,9% (при применении трастузумаба 54,2%; p=0,049). Высокодостоверной оказалась зависимость частоты bpCR от обнаружения кластерной амплификации (81% при ее обнаружении и 48,9% при ее отсутствии; p=0,013). Кроме того, кластерная амплификация гена HER2 была единственным значимым фактором-предиктором достижения полного регресса первичной опухоли и лимфатических узлов: при ее наличии частота tpCR достигла 68,8% против 38,7%.Наличие кластерной амплификации гена HER2 является наиболее значимым фактором чувствительности к анти-HER2-терапии при РМЖ II-III стадии, ассоциируется с максимальной частотой достижения полного лечебного патоморфоза как первичной опухоли в молочной железе, так и регионарных метастазов. Дальнейшее изучение данного фактора может помочь оптимизации лечебного алгоритма при HER2 + РМЖ.

Molecular and biological features of triple negative breast cancer (TN BC) determine the limited possibilities of systemic therapy and, as a consequence, the more aggressive course of the disease. Taxanes are one of the most effective chemotherapies used in breast cancer therapy. The special form of paclitaxel nab-paclitaxel makes it possible to obtain an objective and a subjective effect, which is especially important in the pre-treated patients. In addition, the drug has a favourable safety profile and a well-controlled toxicity.The article contains a review of the literature on the prospects for the use of nab-paclitaxel in breast cancer, especially in its triple negative version, and a description of the clinical case of therapy with a combination of cisplatin and nab-paclitaxel in a young patient with BRCA-1-associated TN breastcancer.

The survival of patients even with disseminated disease reached 7–8 years after introduction of imatinib and sunitinib for the treatment of gastrointestinal stromal tumours (GIST) into everyday clinical practice. These drugs efficacy is largely determined by the presence and any mutations of C-KIT and PDGFR genes. It was established that new mutations appear in most tumours against the background of tyrosine kinase inhibitors therapy, which causes the development of secondary resistance and the progression of the disease in most cases. The search for opportunities to overcome the newly developed or initially existing resistance caused by different gene mutations continues to be of vital importance. One of such drugs is regorafenib, which has demonstrated antitumour activity against progression on imatinib and/or sunitinib. The paper reviews the studies of the efficacy of regoraphanib in patients with disseminated GIST, taking into account the presence and any mutations of C-KIT and PDGFR genes, and presents a description of their own clinical case of prolonged use of the drug in a patient who have received earlier both imatinib and sunitinib.

Background.Working out of the second line chemotherapy of advanced gastric adenocarcinoma is a promising approach to cancer therapy. Ramucirumab, an anti-angiogenic agent specifically targeting vascular endothelial growth factor receptor-2 (VEGFR-2). In April 2014, the FDA approved ramucirumab as a single agent or in combination with paclitaxel for treatment of advanced gastric or gastroesophageal junction adenocarcinoma that has progressed on or after prior fluoropyrimidineor platinum containing chemotherapy based on data of REGARD and RAINBOW trials.Materials and Methods: From June 2016 to 15Jan 201837 pts with advanced GC were treated with ramucirumabin the second line treatment as single agent (11 pts) or in combination with paclitaxel (26 pts) in N.N.Blokhin National medical research center of oncology.Results: edian PFS (MPFS) and median OS (MOS) was 1,8 and 7,6 mons for monotherapy group. For combination group MPFS was 4,0mons, MOS -10,6 mons. Ramucirumab had an acceptable safety profileConclusions:ur data are similar to the data of international randomized trials.

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.

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.

Renal cancer morbidity grows in most of the developed countries. Incidence of bilateral renal cell carcinoma, per various authors, amounts to 2–6 % of all cases of this disease. The study included 160 patients with bilateral kidney cancer who received surgical treatment at the N.N. Blokhin National Medical Research Center of Oncology in the period from 1996 to 2014. Median follow-up duration for all patients included in the analysis was 81.05 ± 46.7 months. In our study, the groups for synchronous and metachronous cancer were equal (n = 80) and constituted 3.5 % of all cases of kidney cancer. For synchronous and metachronous cancer types, the most common concomitant disease was arterial hypertension. The most common morphological variant for the first, as well as the second, kidney tumor was clear cell carcinoma. Smoking and ischemic heart disease as a concomitant pathology negatively affected relapse-free and overall survival. Overall 5-year survival for synchronous renal cancer was 84.4 ± 4.2 %, for metachronous – 64.8 ± 9.3 %.

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

The HannaH study showed that neoadjuvante-adjuvant subcutaneous and intravenous trastuzumab have similar efficacy and tolerability in patients with early HER2-positive breast cancer. The analysis of the results of the subcutaneous and intravenous trastuzumab usage in Russian population showed the favorable association between tpCR anf EFS. tpCR achiviement is associated with clinical benefit in HER2 positive breast cancer. For patients with difficult venous access who do not require intravenous chemotherapy currently, Subcutaneous trastuzumab allows to receive effective treatment without the risk of complications, which involves catheterization of a Central vein.

Tamoxifen is the drug of choice for endocrine therapy of hormone receptor- positive breast cancer in women in the reproductive period. The metabolic activity of tamoxifen is determined by the activity of the enzyme CYP2D6, encoded by the gene of the same name: under the action of the enzyme, tamoxifen passes into the metabolically active form, endoxyphene. Pharmacogenetic testing of the CYP2D6 gene in patients with hormone-positive breast cancer can help predict the effectiveness of therapy and assess the risk of side effects with the aim of improving long-term treatment outcomes.

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.

Treatment of patients with metastatic breast cancer (BC) with a triple-negative phenotype represents the most difficult challenge for clinicians. The optimal chemotherapy regimens for triple-negative BC (TNBC) have not been determined for a long time. However, in the later periods were found molecular agents of application (6 subtypes of TNBC) for the specific therapeutic agent and were performed many studies and subunit analysis, examined appropriate drugs for TNBC. Cell lines of these subtypes have different anticancer drug sensitivity. The results of further studies of targeted drugs using as monotherapy or in combination with chemotherapy in patients with TNBC, in spite of molecular genetic evidence for their application, have fallen short of expectations, although have shown increase in progression-free survival and overall survival. The development of eribulin (nontaxane microtubule dynamics inhibitor) in 2010 significantly increased the possibility of therapy in patients with locally advanced and metastatic BC who had already received chronic treatment. According to the joint analysis of the randomized phase III EMBRACE trial and Study 301, which included data about 1864 patients, it was demonstrated that eribulin statistically significant improve overall survival compared with other drugs using as monotherapy in the general population and among patients with TNBC [statistically significant differences in overall survival was associated with the subgroup of TNBC in patients who had been treated with eribulin, in comparison with the control arm: 12.9 and 8.2 months, respectively (relative risk 0.74; 95% confidence interval, 0.60 to 0.92, p=0.006)]. This article deals with the own experience of successful and long-term eribulin application in young woman with TN metastatic BC who have had already received chronic treatment.

Treatment of patients with metastatic breast cancer (BC) with a triple-negative phenotype represents the most difficult challenge for clinicians. The optimal chemotherapy regimens for triple-negative BC (TNBC) have not been determined for a long time. However, in the later periods were found molecular agents of application (6 subtypes of TNBC) for the specific therapeutic agent and were performed many studies and subunit analysis, examined appropriate drugs for TNBC. Cell lines of these subtypes have different anticancer drug sensitivity. The results of further studies of targeted drugs using as monotherapy or in combination with chemotherapy in patients with TNBC, in spite of molecular genetic evidence for their application, have fallen short of expectations, although have shown increase in progression-free survival and overall survival. The development of eribulin (nontaxane microtubule dynamics inhibitor) in 2010 significantly increased the possibility of therapy in patients with locally advanced and metastatic BC who had already received chronic treatment. According to the joint analysis of the randomized phase III EMBRACE trial and Study 301, which included data about 1864 patients, it was demonstrated that eribulin statistically significant improve overall survival compared with other drugs using as monotherapy in the general population and among patients with TNBC [statistically significant differences in overall survival was associated with the subgroup of TNBC in patients who had been treated with eribulin, in comparison with the control arm: 12.9 and 8.2 months, respectively (relative risk 0.74; 95% confidence interval, 0.60 to 0.92, p=0.006)]. This article deals with the own experience of successful and long-term eribulin application in young woman with TN metastatic BC who have had already received chronic treatment.

e12581 Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Pathologic complete response (pCR) achievement during neoadjuvant chemotherapy (NACT) is very important for these pts as it correlates with long-term outcome. Predictive and prognostic factors for this group of pts are needed. Methods: Since 2014 we treated 98 pts with histologically confirmed stage II-III TNBC with following regimen of NACT: 6 cycles of Cisplatin 75mg/m2 day 1 and Paclitaxel 80mg/m2 days 1, 8, 15, every 4 weeks according to local protocol. After NACT pts proceeded to radical breast surgery with assessing of pathological response. Before the treatment we assessed TILs in biopsy samples of all patients. We also conducted subpopulation analysis of lymphocytes in peripheral blood before treatment. We analyzed CD8+, CD25+, NK and NKT cells as they were reported to be significant earlier. We compared results with median value in reference group (mRG) of healthy women. Results: Among all 98 pts 86 (87%) were operated, pCR was achieved in 60,5% of operated pts. pCR strongly correlated with TILs level: 38,5% for pts with TILs < 5% and 69,8% for pts with TILs > 5% (p = 0,05). We also found that NKT population was associated with pCR: 77,8% vs 45,8% among patients with NKT above mRG and up to mRG, respectively (p = 0,01). It correlated also with tpCR: 22,2% vs 70,6% (p = 0,01). When both CD25+ and NKT population were above mRG pCR rate achieved in 85,7% pts vs 50,0% pts if it was up to mRG (p = 0,049). NK, CD8+ and CD25+ did not show any correlation with pCR. Survival results are presented in table below. NK, NKT and TILs did not show any correlation with survival. Interestingly, CD8+ were also associated with lower incidence of visceral metastases: 42,1% in pts with normal CD8+ and 15,7% in pts with CD8+ above normal (p = 0,19). Conclusions: Not only TILs, but also NKT and CD25+/NKT population in the peripheral blood could be possible predictive factors for patients with stage II-III TNBC receiving NACT. CD8+, CD25+ and NKT populations could be further studied as prognostic markers for this group of patients. [Table: see text]

e12613 Background: Breast cancer is in first place among malignant diseases in women in Russia. We can provide, in most cases, breast-conserving surgery (BCS), due to progress in early diagnosis. Evaluation of positive margins is still one of the most important objectives in breast-conserving surgery. Objectives: To assess the benefits of IDSR in BCS of patients with “carcinoma in situ”. Methods: The results of treatment of 55 patients with breast cancer “carcinoma in situ” in our clinic were evaluated in two comparable groups. Group A included 28 patients, who were operated on from January 2019 to June 2019 and had breast-conserving surgery without IDSR. Group B included 27 patients, who were operated on from June 2019 to January 2020 and had breast-conserving surgery with the evaluation of margins by IDSR. Results: In a planned histological examination positive margins were detected in group A in 4 cases (14%) and required reoperation. In group B all margins were clear. After IDSR, 6 (22%) patients out of 27 in this group showed microcalcifications in the resection margins or at a distance of less than 1 mm and required intraoperative additional excision to obtain clean margins. Conclusions: IDSR reduces the frequency of reoperation due to increased detection of positive margins, allows to correct scope and duration of surgery because of impact on the time of the surgical decision-making process.

The aim of this study was to investigate the relationship between the original amount of basic lymphocyte subpopulations in peripheral blood and the results of therapy in patients with HER2+ and triple negative breast cancer. Before treatment was conducted immunophenotyping of peripheral blood lymphocytes by flow cytometry using a panel of monoclonal antibodies to surface markers and intracellular lymphocyte antigen FOXP3 and determining the cytotoxic activity of NK-cells. Cytotoxic activity was determined with MTT colorimetric test against K-562 cells. Revealed some differences in the composition of the population of lymphocytes and the number of regulatory T cells in patients with HER2+ and triple negative breast cancer (BC). Discuss the relationship between the number of suppressor cells and the degree of therapeutic pathomorphosis of tumor.

5–10 % of breast cancer cases are hereditary, 30 % of them are caused by BRCA1 and BRCA2 mutations (breast / ovarian cancer syndrome). Average cumulative risks of breast and ovarian cancer in BRCA1 mutation carriers run up to 87 % and 44 %, correspondingly. The risk for contralateral breast cancer is also high: after 25 years, 62.9 % of patients with BRCA1 mutation who were younger than 40 years of age at first breast cancer develop contralateral breast cancer. The role of single nucleotide polymorphisms in BRCA1 and BRCA2 genes modifying breast and gynaecological cancer risks is actively studied. Genetic testing is performed as a part of genetic counselling. The main inclusion criteria are multiple affected family members with breast / ovarian cancer, breast cancer at young age (under 35–50 years), ovarian cancer at any age, male breast cancer, morphological features of breast cancer (triple-negative, medullar tumors), ethnicity (Jewish ancestry). High-risk individuals carrying BRCA mutations undergo specific surveillance, chemoprophylaxis and surgery protocols. Prophylactic bilateral mastectomy reduces breast cancer risk by 90–94 %.

In breast cancer, bone metastases are detectable in more than 60 % of patients. Bone metastasis-related complications (BMRCs), such as chronic pain, immobilization, and pelvic dysfunctions due to spinal cord compression, considerably worsen quality of life in patients. Intra- venous formulations of bisphosphonates (zoledronic acid, pamidronate, ibondronate, and clodronate) could reduce the risk of BMRCs by 16-40 % and increase time to the first skeletal complication up to 12–13 months. However, despite the explicit clinical efficacy of bisphospho- nates, the latter can seemingly prevent only some BMRCs. Denosumab, a fully human monoclonal antibody to RANKL, suppresses the forma- tion and functional activity of osteoclasts, thus inhibiting bone resorption.The results of a registration study have indicated that denosumab is not only as effective as zoledronic acid, but also can reduce the risk of BMRCs and significantly delay time to the first and further skeletal complications, including the need for radiotherapy, the development of hypercalcemia and pathological fractures. Denosumab is an effective, well-tolerated drug that can increase a chance of preventing BMRCs in breast cancer.

e12102 Background: Effect of neoadjuvant chemotherapy (NACT) is extremely important for patients with HER2-positive breast cancer stage II-III as it correlates with long-term outcomes. However, predictive factors for achieving complete pathologic response (pCR) remain unclear. Aim of the study: Assess an impact of clinical, morphological and genetic factors on pCR achievement in patients with HER2-positive breast cancer stage II-III treated by biosimilar of trastuzumab. Methods: We studied treatment results in 73 patients with HER2-positive breast cancer (BC) stage II-III (aged 29-71, median – 51 years), treated with NACT with anti-HER2 therapy and radical surgery in “N.N. Blokhin National Medical Research Center of Oncology” оf the Ministry of Health of the Russian Federation in 2015-2018. After radical surgery pathologic response was assessed. Initially operable tumors were observed in 45,2% patients, locally advanced - in 53,4%. Luminal HER2-positive BC was diagnosed in 41,1%, non-luminal HER2-positive in 58,9%. Ki67 was high (≥ 20%) in 91,5%. NACT included anthracycline and non-antracycline regimens with addition of biosimilar of trastuzumab ± pertuzumab. Radical mastectomy was performed in 78,8% patients, 21,2% had breast-conserving surgery. We studied biopsies obtained before the start of treatment in all women, HER2 amplification was detected by HER2 IQFISH pharmDx (DAKO) kit in accordance with ASCO/CAP 2018 guidelines. In 87,1% HER2+ status was defined as ASCO/CAP 2018 category 1; cluster amplification was detected in 30,1% patients. We analyzed the rate of bpCR и tpCR achievement depending on clinical, pathological data and amplification of HER2. Results: Pathologic complete response in primary tumor (bpCR) was achieved in 57,4%, both in primary tumor and lymph nodes (tpCR) – in 48,9% patients; bpCR achievement depended on age, NACT regimen, addition of pertuzumab and HER2 copy number ( < 0,05). The highest rate of bpCR was noted in women aged 50 and older (71,9%, p = 0,026); in patients received TCH±Р regimen (80,0%, p = 0,045); with addition of pertuzumab (88,9%, p = 0,049); and if cluster amplification was detected (81%, p = 0,013). Cluster amplification was the only one significant predictive factor for achieving tpCR: with cluster amplification - 68,8%, without - 38,7% (p = 0,049). Conclusions: Cluster amplification of HER2 is the most significant factor of especial sensitivity for NACT with biosimilar of trastuzumab in HER2-positive BC stage II-III.

OBJECTIVE To evaluate the influence of clinical and morphological factors and HER2 copy numbers on pathologic complete response (pCR) rates in patients with HER2-positive stage II-III breast cancer (BC). MATERIAL AND METHODS Treatment results were studied in 73 patients with HER2-positive Stage II-III BC, who received treatment at the N.N. Blokhin National Medical Research Center of Oncology in 2015 to 2018. Treatment included neoadjuvant chemotherapy (NACT) with HER2-blockade and radical surgery followed by the evaluation of a pathologic response in the primary tumor and regional lymph nodes. The patients` age varied from 29 to 71; its median was 51.5; 45.2% of patients had primary operable stages (T1-3N0-1) and 54.8% had locally advanced tumors. All the patients had grade 2-3 anaplasia; luminal HER2-positive BC was diagnosed in 41.4% of patients; hormone-negative tumors were seen in 58.9%; 91.5% of patients had Ki-67 ≥20% in 75.3% of patients, preoperative systemic therapy included anthracycline-containing regimens (4AC + 4 x paclitaxel 175 mg/m2/12 × weekly administrations of paclitaxel 80 mg/m2; trastuzumab therapy was simultaneously performed with the administration of taxanes in the standard regimen) and anthracycline-free regimen TCH ± Pertuzumab regimen in 24.7% of cases. After NACT patients underwent surgery (radical mastectomy in 78.1%, breast-sparing treatment in 21.9%) with the assessment of morphological findings. Biopsy specimens obtained before the treatment was restudied; HER2 amplification was detected using a Dako HER2 IQFISH pharmDx kit according to its instruction and the 2018 ASCO/CAP guidelines. In 87.1% of cases, the HER2-positive status corresponded to the first category of the 2018 ASCO/CAP criteria for HER2-positive BC; clustered HER2 amplification was found in 30.1% of cases. The authors analyzed the frequency of bpCR and tpCR attainment by various clinical and morphological factors, as well as the impact of a HER2 amplification level on pCR rates. RESULTS A breast pCR (bpCR) was achieved in 57.4% patients; bpCR and lymph node CR (lnCR) were noted in 48.9% patients. The rates of bpCR significantly depended on female age, chemotherapy regimen, addition of Pertuzumab, and HER2 copy number. That of bpCR in women less than 35 years of age, in those aged 36-50 years, and in those aged older than 50 years was 22.2, 57.7 and 71.9%, respectively (p=0.026). The maximum bpCR rate observed with the TCH±P regimen was 80.0%, that with anthracycline-containing regimes was 52.8% (p=0.045), and the addition of Pertuzumab increased complete response rates up to 88.9% (that with Trastuzumab was 54.2% (p=0.049). The relationship of bpCR rates to the detection of cluster amplification turned out to be highly significant (81% in its detection and 48.9% in its absence (p=0.013). In addition, clustered HER2 amplification was the only significant predictive factor for complete regression in the primary tumor and lymph nodes: in its presence, the tpCR rate reached 68.8% versus 38.7%. CONCLUSION Clustered amplification of the HER2 gene is the most significant factor of sensitivity to anti-HER2 therapy for Stage II-III BC, and is associated with the maximum rate of both bpCR and total pCR. Further study of this factor may assist in optimizing the treatment algorithm for HER2 + BC.

Objectives: discussion of modern treatment options for metastatic breast cancer (MBC), the determining of the optimal treatment for subgroups of patients with poor prognosis.

e13025Background: HER2 amplification/overexpression is a prognostic and predictive factor for the development of breast cancer (BC) metastases to central nervous system. Anti-HER therapy improve ov...