Современные подходы к системному лечению BRCA-ассоциированного трижды негативного рака молочной железы

BRCA-associated triple-negative breast cancer (TNBC) is characterized by high sensitivity to DNA-damaging cytotoxic drugs. The use of well-known BRCA1/2-specific antitumor agents – platinum derivatives and PARP inhibitors – has been discussed for a long time in the context of the treatment of metastatic BRCA-associated TNBC. Neoadjuvant regimens based on the use of anthracyclines and taxanes are the standard of drug therapy for primary BRCA-associated breast cancer. At present, there are few data regarding the addition of platinum drugs to anthracycline-taxane neoadjuvant chemotherapy in the treatment of primary BRCA-associated TNBC. This review details the various treatment options for both primary and metastatic BRCA-associated TNBC. It has been shown that the development of new strategies for the neoadjuvant chemotherapy of patients with primary BRCA-associated TNBC is an urgent clinical need to reduce the risks of recurrence and progression.BRCA-ассоциированный трижды негативный рак молочной железы (ТНРМЖ) характеризуется высокой чувствительностью к ДНК-повреждающим цитотоксическим препаратам. Применение известных BRCA1/2-специфических противоопухолевых средств – производных платины и PARP-ингибиторов – длительное время обсуждалось в контексте лечения метастатического BRCA-ассоциированного ТНРМЖ. Стандартом лекарственной терапии первичного BRCA-ассоциированного РМЖ является неоадъювантная химиотерапия с использованием антрациклинов и таксанов. В настоящее время имеется не так много данных о добавлении препаратов платины к антрациклин-таксановой неоадъювантной химиотерапии при лечении первичного BRCA-ассоциированного ТНРМЖ. В представленном обзоре подробно описаны различные способы терапии данного рака, как первичного, так и метастатического. Показано, что разработка новых стратегий неоадъювантной химиотерапии для пациенток с первичным BRCA-ассоциированным ТНРМЖ является насущной клинической необходимостью для снижения рисков рецидивирования и прогрессирования

Может ли блокировка андрогенных рецепторов стать основой нового способа лечения трижды негативного рака молочной железы?

Triple-negative breast cancer (TNBC) represents approximately 15% –20% of all diagnosed breast cancers. This tumor subtype characterized by the absence of expression of the estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor (HER2) protein. Tumor heterogeneity of triple negative breast cancer is the main barrier in the treatment of this tumor subtype. Although estrogen receptor (ER) and human epidermal growth factor receptor (HER2) are the mainstay therapeutic targets in breast cancer, the androgen receptor (AR) is evolving as a molecular target for cancers that have developed resistance to conventional treatments.Tрижды негативный рак молочной железы (ТНРМЖ) составляет примерно 15%-20% от всех диагностированных случаев рака молочной железы и характеризуетсяотсутствием экспрессии рецепторов эстрогена (ЭР), рецепторов прогестерона (ПР), а также отсутствием экспрессии белка человеческого эпидермального фактора роста (HER2) белка. Гетерогенность трижды негативного рака молочной железы является основным препятствием в лечении данного подтипа опухоли. Хотя рецепторы эстрогенов (ЭР) и рецептор человеческого эпидермального фактора роста (HER2) являются основными терапевтическими мишенями при раке молочной железы, рецептор андрогена (AR) в последнее время получил развитие в качестве молекулярной мишени в лечении опухолей, резистентных к стандартным способам лечения

БИОПСИЯ СИГНАЛЬНЫХ ЛИМФАТИЧЕСКИХ УЗЛОВ ПРИ РАКЕ МОЛОЧНОЙ ЖЕЛЕЗЫ

За последние десятилетия в хирургическом лечении рака молочной железы появилась тенденция к органосохраняющему и все менее травматичному и калечащему этапу в многоступенчатой терапии этого заболевания. Выполнение подмышечной лимфодиссекции часто сопровождается такими осложнениями, как лимфостаз верхних конечностей, ограничение подвижности и болевые ощущения плечевого сустава, что, в ряде случаев, ведет к инвалидизации, при излечении от рака

Новообразования молочной железы с неопределенным потенциалом злокачественности (B3): опыт применения вакуум-ассистированной биопсии под ультразвуковой навигацией

INTRODUCTION: Introduction of breast cancer screening programs has led to an increase in detection of non-palpable masses requiring core needle biopsy. Masses that fall into B3 category based on the histological results of core biopsy specimens, are of interest precisely because of their uncertain malignant potential and the lack of a final consensus on their management.OBJECTIVE: To analyze the 3-year experience of ultrasound guided vacuum-assisted biopsy (VAB) in patients with B3 breast lesions based on the results of histological examination of core biopsy specimens.MATERIALS AND METHODS: Between June 2019 and June 2022, 163 VABs were performed. The study group included patients with category 2–4 breast lesions according to the BI-RADS scoring system. The decision to perform VAB was made by the oncologist in each specific case on the basis of anamnesis, clinical data and the results of core biopsy histological examination: in cases of B3 or B2 lesions with a discordant radiologic pattern.RESULTS: In 155 (95.0%) cases, the removed lesions were benign, invasive cancer was detected in 2 (1.2%) cases, ductal cancer in situ in 6 cases (3.8%). The сomplications included: in 5 (3.1%) cases, patients had pain after the procedure, and in 37 (22.7%) cases there was a hematoma. In 5 (3.1%) patients, residual tissue was found at the site of removed lesions. CONCLUSIONS: VAB is a safe alternative to exploratory surgery in patients with B3 lesions diagnosed by core biopsy.ВВЕДЕНИЕ: Внедрение программ скрининга рака молочных желез привело к увеличению частоты обнаружения непальпируемых образований, требующих проведения трепан-биопсии. Новообразования, попадающие в категорию B3, согласно результатам гистологического исследования трепанбиоптатов, вызывают интерес именно из-за их неопределенного потенциала злокачественности и отсутствия окончательного консенсуса дальнейшей тактики.ЦЕЛЬ: Проанализировать 3-летний опыт применения вакуум-ассистированной биопсии (ВАБ) под ультразвуковым контролем у пациенток с очаговыми новообразованиями молочных желез при полученных результатах гистологического исследования трепан-биоптатов.МАТЕРИАЛЫ И МЕТОДЫ: В период с июня 2019 г. по июнь 2022 г было выполнено 163 ВАБ. В группу исследования вошли пациентки с новообразованиями молочных желез категорий 2–4 по шкале BI-RADS. Решение о выполнении ВАБ принималось онкологом в каждом конкретном случае на основании анамнестических, клинических данных и результатов гистологического исследования трепан-биоптатов: при определении образований категории В3 или В2 при дискордантной лучевой картине.РЕЗУЛЬТАТЫ: В 155 (95,0%) случаях удаленные новообразования имели доброкачественный характер, инвазивный рак выявлен в 2 (1,2%) случаях, протоковый рак in situ — в 6 случаях (3,8%). Осложнения: в 5 (3,1%) случаях после проведенной процедуры у пациенток имелся болевой симптом, а в 37 (22,7%) случаях проведение процедуры сопровождалось появлением гематомы. У 5 (3,1%) пациенток была выявлена остаточная ткань в зоне удаленных новообразований.ЗАКЛЮЧЕНИЕ: Вакуум-ассистированная биопсия является безопасной альтернативой диагностической хирургии у пациенток с поражениями категории B3, диагностированными при трепан-биопсии

COMPARATIVE ANALYSIS OF DIFFERENT NEOADJUVANT CHEMOTHERAPY REGIMENS FOR TRIPLE-NEGATIVE BREAST CANCER

Background. Breast cancer is a heterogeneous disease with a variety of phenotypic forms. Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes characterized by high sensitivity to chemotherapy and early recurrence. Due to the lack of efficiency of standard therapeutic approaches, it appears extremely important to search for new regimens of neoadjuvant polychemotherapy (NAPCT). Objective: to assess the efficiency of different NAPCT regimens for treatment of stages T1N1–3 and T2–4N0–3 locally advanced TNBC and to compare the efficiency of eribulin and paclitaxel in NAPCT of TNBC.Materials and methods. A randomized prospective study to evaluate the efficacy of TNBC treatment is being conducted in the N.N. Petrov National Medical Research Center of Oncology since October, 2015. The study included 61 patients with a median age of 45 years (range 31–76 years). Study participants were treated with 2 different NAPCT regimens: patients in the 1st group received eribulin at a dose of 1.1 mg/m2 on the days 1 and 8 of a 21-day cycle in combination with carboplatin AUC6, patients in the 2nd group received paclitaxel at a dose of 80 mg/m2 on the days 1 and 8 of a 21-day cycle in combination with carboplatin AUC6. Then all patients underwent surgery in different volume (radical mastectomy, organ-preserving surgery, reconstructive plastic surgery) with subsequent FAC adjuvant chemotherapy.Results. So far, 61 patients have been randomized (further calculations are based on the number of operated patients: 24 in the 1st group and 27 in the 2nd group). During the preoperative stage, complete clinical regression was achieved in 11 patients from the 1st group and 15 patients from the 2nd group; partial clinical regression was observed in 13 and 12 patients in groups 1 and 2 respectively. We found that the therapeutic regimen with paclitaxel + carboplatin induced a higher rate of pathologic complete responses (ypCR). After NAPCT, 51 out of 61 patients (84 %) underwent surgical treatment. Pathomorphological examination showed that the frequency of pathologic complete response was 33 % (8 cases) in the 1st group compared to 60 % (16 cases) in the 2nd group. Five patients treated with eribulin + carboplatin developed distant metastases in bones, lungs, brain, postoperative scar and lymph nodes in the neck on average 4 months after surgery.Conclusions. Higher rate of ypCR was observed in patients received paclitaxel + carboplatin

Twenty-year experience of examining biopsies of signal lymph nodes in breast cancer

Biopsy of signal (sentinel) lymph nodes (LN) has been performed at the N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia, for almost 20 years. In the first few years, contrast-visual method (1 % blue isosulfan and triphenyl methane control) was used in 640 patients with early (T1–2N0M0) breast cancer. In 150 patients from this cohort, standard axillary dissection was performed irrespectively of the results of signal (sentinel) biopsy. The rate of false positive responses varied between 4.6 and 6.6 %. Since 2012, radioisotope method of visualization of signal LN with intratumor administration of 99mТс-technephyte colloid particles has been used (in 708 patients with T1–3N0M0 breast cancer). This type of signal LN biopsy had the following diagnostic characteristics: sensitivity was 58.9 %, specificity was 96.2 %, diagnostic accuracy was 87.1 %.In parallel with this study, in 2016 a study of diagnostic accuracy and safety of biopsy of axillary LN after neoadjuvant systemic therapy was started. The study included 263 patients with T1N1–3M0, T2–3N0–3M0, T4N0–1M0 breast cancer. To evaluate clinical status of axillary LN, ultrasound, single-photon emission computed tomography, mammography at baseline and after completion of neoadjuvant chemotherapy ± targeted therapy (trastuzumab) were performed. In some patients, in the recent years a double method of signal LN labeling (radioisotope and fluorescent methods) was used.In patients with baseline cN+-status, the rate of false positive signal LN biopsy conclusions was 13.6 %, in patients with baseline cN0-status it was 7.7 %.The study of double contrast of axillary LN and targeted label of metastatic LN prior to neoadjuvant systemic therapy continues. In total, various modifications of biopsy of signal LN were performed in 2,000 patients with breast cancer.The study protocol was approved by the biomedical ethics committee of N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia.All patients gave written informed consent to participate in the study

Immediate breast reconstruction using titanised mesh

Additional covering of the lower pole with allomaterial or its synthetic analogues during immediate breast reconstruction is being performed at the N. N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia, for last 7 years. Initially, epidermal flap was the only option for lower pole coverage; later acellular dermal matrix was used as part of clinical approbation. Average complication rate ranges from 20–35 % due to blood circulatory (supply) disorders.Since 2018, a titanised mesh been used as an additional coverage of the lower pole in the department of breast tumors. Through coating characteristics and its structure the frequency of fatal complications significally decreased