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.
e13008 Background: TNBC is associated with aggressive behavior and poor prognosis. TNBC is the most common subtype seen in patients with hereditary BRCA associated breast cancer. Because of defects of homologous recombination these tumours may be extremely sensitive to DNA-damaging agents such as platinum. Little is known about influence of different germline BRCA mutations on response to chemotherapy. Previously we have shown that somatic BRCA1 mutations may determine different responses to platinum-based chemotherapy. Now we analyse efficacy of dose-dense schedule of doxorubicin, cisplatin and paclitaxel in pts with hereditary BRCA associated TNBC. Methods: Twenty eightpts with early (cT1-2N0-1M0) and locally advanced (cT2-4N2-3M0) hereditary BRCA associated TNBC were treated with dose-dense combination of doxorubicin, cisplatin and paclitaxel followed by surgery. Mutations distribution is summarized in table 1. Pathological response was evaluated according to the Chevallier classification. Results: Median agewas 37 (25-56) years, 45% of pts had tumor Grade 3, median Ki67 was 70%. All pts completed chemotherapy and underwent surgery. Pathological complete response (pCR) was achieved in 18 pts (64,3%). All pts with BRCA2 mutations, with BRCA1 LOH, BRCA1 185delAG and majority (12/17) of pts with BRCA1 5382insC mutations achieved pCR. Whereas all pts with BRCA1 C61G, BRCA1 4094T>G and 2/3 pts with BRCA1 4153delA mutations had residual disease. Conclusions: BRCA mutations may predispose different responses to platinum-based chemotherapy. Clinical trials with larger number of pts are required. Mutations distribution. BRCA mutation N=28 n (%) Pts with pCR n/N BRCA1 5382insC 17 (60,7) 12/17 BRCA1 185delAG 1 (3,6) 1/1 BRCA1 C61G 2 (7,1) 0/2 BRCA1 4153delA 3 (10,7) 1/3 BRCA1 4094T>G 1 (3,6) 0/1 BRCA1 loss of heterozygosity (LOH) 2 (7,1) 2/2 BRCA2 N372H 1 (3,6) 1/1 BRCA2 6174T/delT 1 (3,6) 1/1
Nab-паклитаксел представляет собой наночастицу паклитаксела, связанную с альбумином. В отличие от стандартных таксанов (паклитаксел, доцетаксел), в составе nab-паклитаксела отсутствуют растворители, что снижает риск развития реакций гиперчувствительности и других побочных явлений. При использовании nab-паклитаксела не требуется проведения премедекации глюкокортикоидами и антигистаминными препаратами. Кроме того, в ряде экспериментов было показано, что применение nab-паклитаксела позволяет создать более высокую концентрацию препарата в опухоли. В статье освещены основные исследования применения nab-паклитаксела в различных дозах и режимах введения при метастатическом раке молочной железы. Приведен возможный алгоритм оптимального режима введения nab-паклитаксела для различных клинических ситуаций.
In recent years, there has been a wide range of treatment options for patients with metastatic HER2-positive breast cancer, resulting in the highest life expectancy for these patients among all subtypes. The addition of pertuzumab to trastuzumab and docetaxel has been shown to increase overall survival and is therefore recognized as the standard first-line treatment. The most optimal second-line treatment option is trastuzumab emtansine. In addition, various combinations of cytostatics and anti HER2 targeting agents can be used. The choice of treatment options in heavily pretreated patients is of great interest. If they have not previously received pertuzumab, is it worth to use it and which combination is the best? One possible option is the combination of eribulin with the dual anti-HER2 blockade with trastuzumab and pertuzumab. Eribulin is an anti-microtubule agent that irreversibly blocks mitosis. In addition, it has non-mitotic effects – in vivo and in vitro experiments demonstrated its ability to restore normal tumor vascularization, reduce the area of hypoxia and, as a consequence, decrease tumor cells migration and invasion. This article represents a clinical case of the use of eribulin with double anti-HER2 blockade in the 6th line of treatment in a patient with metastatic HER2-positive breast cancer. Long-term control of the disease (within 2 years) with a satisfactory quality of life has been demonstrated.
One of the common stages of technological processing of products is refining. In the refining process, socalled "ballast substances" are removed from the initial product. As a rule, vitamins, microelements, amino acids and other useful biologically active substances - antioxidants get into the ballast, and food is loaded with trans-fats, saturated fatty acids, etc. The purpose of the work was to assess the impact of nutrition features on some indicators of free radical status in EBC. The study involved young people (20 students) aged 22 to 35 years. During the experiment, the collection of EBC from patients took place several times: after a diet without refined foods and after a diet with a large number of refined foods. In the course of the work, the determination of the total concentration of nitrates/nitrites, as NO metabolites, and the level of iron in EBC was carried out. Antioxidant activity was assessed by catalase activity in EBC. As a result of this work, it was found that a diet with a large number of refined products leads to an increase in the body9s SRO processes (the concentration of nitrates / nitrites increases 3 times - from 2.91 ± 0.23 μM to 8.87 ± 0.32 μM ( P <0.05), and the concentration of iron is 2 times (from 1.29 ± 0.1 μM to 2.74 ± 0.16 μM (P<0.05)). Increased catalase activity in EBC with 0.161 ± 0.119 units. to 0,243 ± 0,019 units. (P <0.05) speaks of the activation and antioxidant system. Thus, the use of a large number of refined, processed products increases the production of free radicals, which is reflected in the performance of EBC. At the same time, an increase in the antioxidant indices of EBC occurs.
According with the present-day ideas, sequential lines of hormone therapy including those in patients with visceral metastases and multiple lesions form the basis of the treatment of HER2-negative metastatic hormone-dependent breast cancer. These measures make it possible to exercise the long-term control of the disease and maintain a good quality of life. In recent years, the clinical practice comprises the next-generation drugs that potentiate the effect of hormone therapy. These include cyclindependent kinases 4/6 inhibitors. Palbociclib (Ibransa, Pfizer) is the first representative of this class approved in Russia for the treatment of disseminated hormone-dependent breast cancer. The PALOMA-2 study demonstrated the high efficacy of the palbociclib combined with letrozole as a first-line hormone therapy. In the palbociclib and letrozole combination arm, the median time to progression was 27,6 months compared to 14,5 months in the letrozole monotherapy arm (p <0,001). The presented clinical case demonstrates the possibility of long-term successful control of the disease using palbociclib combined with letrozole hormone therapy.
e12573 Background: Compared to other breast cancer subtypes, patients (pts) with triple-negative breast cancer (TNBC) have a lower recurrence-free and overall survival, regardless of disease stage at diagnosis. One of the ways to improve the results of treatment of locally advanced (LA) TNBC is intensification of induction chemotherapy regimens. We performed a prospective trial to evaluate efficacy of two consequent induction chemotherapy regimens: рaclitaxel, сarboplatinum weekly, then metronomic doxorubicin, cyclophosphamide and capecitabine (NCT01969032). Methods: Pts with LA TNBC (cТ2-4 N 2-3 M0) were treated with 2 consequent chemotherapy regimens: рaclitaxel 60 mg/m2 IV weekly plus сarboplatinum AUC2 IV weekly for 9 weeks, then doxorubicin 25 mg/m2 IV weekly plus cyclophosphamide 50 mg per os q.i.d. plus capecitabine 500 mg t.i.d for 9 weeks. Pathological response was evaluated according to the Chevallier classification. Results: Forty one pts were included in the study in 2011-2013. Median agewas 50 years (27-69), 33.3% of pts had tumor Grade 3, Ki67 was > 20% in 100% of cases. Forty pts completed chemotherapy. Overall response rate was 87.5% with 14.6% of complete responses and 73.2% of partial responses. Forty pts underwent surgery. Twenty-four pts (60%) achieved pCR. With median follow-up of 37,8 (10.2–55.8+) months, 12/14 (29%) pts had a disease progression: 5/12 (41.6%) with pCR, 6/12 (50%) with residual tumor. Оne pt had a disease progression during chemotherapy and was switched to 2nd-line chemotherapy. Death was registered in 7 (17%) pts.Three-year disease-free survival was 71% and overall survivalwas 82%. The dose-limiting toxicities were neutropenia (22.2% grade 3-4), mucositis (8.3% grade 3) and hand-foot syndrome (5.6% grade 3). In 11 pts treatment was discontinued early due to toxicity. Conclusions: Two consequent induction chemotherapy regimens: рaclitaxel, сarboplatinum weekly, then metronomic doxorubicin, cyclophosphamide and capecitabine shows promising activity in treatment of LA TNBC with acceptable toxicity. Clinical trial information: NCT01969032.
