tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2017-1-5-17tumors-321Research ArticleФУНДАМЕНТАЛЬНАЯ ОНКОЛОГИЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАFUNDAMENTAL ONCOLOGY AND EXPERIMENTAL MEDICINEЭволюция представлений о тройном негативном раке молочной железы: от биологии опухоли к современному лекарственному лечениюThe evolution of knowledge of triple-negative breast cancer: from biology to novel drug treatmentСМИРНОВАО. В.SMIRNOVAO. V.

аспирант 3 года обучения ,онкологии и лучевой терапии,  врач-онколог химиотерапевтического отделения стационара

MD, student, Department of Oncology and Radiology

OlgaSmirnova198@mail.ruБОРИСОВВ. Е.BORISOVV. I.

д.м.н., профессор, зав. отделением амбулаторной химиотерапии с дневным стационаром

MD, PhD, DSc, professor, head of Outpatient Clinic

okd1@zdrav.mos.ruГЕНСГ. П.GENSG. P.

д.м.н., доцент кафедры онкологии и лучевой терапии

MD, PhD, DSc, Department of Oncology and Radiology

gelena974@gmail.comМосковский государственный медико-стоматологический университет им. А.И. Евдокимова, Онкологический Клинический Диспансер № 1РоссияMoscow Oncological Clinical Dispensary № 1, Moscow State University of Medicine and Dentistry named after A. I. EvdokimovRussian FederationОнкологический Клинический Диспансер № 1РоссияMoscow Oncological Clinical Dispensary № 1Russian FederationМосковский государственный медико-стоматологический университет им. А.И. ЕвдокимоваРоссияMoscow State University of Medicine and Dentistry named after A. I. EvdokimovRussian Federation20170107201701517Copyright © СМИРНОВА О.В., БОРИСОВ В.Е., ГЕНС Г.П., 20172017СМИРНОВА О.В., БОРИСОВ В.Е., ГЕНС Г.П.SMIRNOVA O.V., BORISOV V.I., GENS G.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/321

Тройной негативный рак молочной железы (ТНРМЖ) характеризуется отсутствием  экспрессии рецептором эстрогенов, прогестерона и HER2. Клинически ТНРМЖ отличается агрессивным течением, ранним метастазированием в отдаленные органы, плохими показателями общей выживаемости по сравнению с другими подтипами рака молочной железы. Молекулярно-генетические исследования позволили выделить различные молекулярные подтипы ТНРМЖ (базальноподобный, подтип с низкой экспрессией клаудина), продемонстрировали наличие так называемых «иммуно-активированных» подтипов, которых отличает более благоприятный прогноз. Кроме того, дальнейшие исследования охарактеризовали ТНРМЖ с молекулярной точки зрения, включая высокую частоту TP53 мутаций, активацию PI3K и MEK сигнальных путей, отсутствие функции RB1 белка, генетическое сходство с раком яичников, заключающееся в инактивации BRCA сигнального пути. Знания о генетической неоднородности ТНРМЖ привело к многообещающим открытиям в лекарственном лечении, включая использование при этих опухолях ДНК- повреждающих агентов (препараты платины и PARP ингибиторы), а также иммунотерапию в настоящее время. Препараты платины становятся стандартными компонентами в схемах химиотерапии при метастатическом ТНРМЖ. Наилучшие результаты при лечении препаратами платины получены у пациентов с выявленной BRCA-мутацией. Кроме того, использование препаратов платины в неоадъювантных режимах у пациентов с ТНРМЖ приводит к повышению частоты полного ответа. Присутствие в тканях тройных негативных опухолей инфильтрирующих лимфоцитов несет прогностически значимую роль. Использование ингибиторов контрольных точек, включая ингибиторы PD-1 и PD-L1, активно исследуется при метастазах ТНРМЖ. Для и PD-L1, активно исследуется при метастазах ТНРМЖ. Для клиницистов большое значение имеет возможность назначать пациентам с ТНРМЖ оптимальные схемы лекарственного лечения, основанные на знаниях о различных подтипах ТНРМЖ, что в итоге позволит достичь высоких показателей общей и безрецидивной выживаемости.

Triple-negative breast cancer (TNBC) is definied by the lack of expression of the estrogen receptor, progesterone receptor and HER2. TNBC has been characterized by aggressive course,early development of metastases, poor overall survival rates compared to other subtypes of breast cancer. Molecular genetic studies have allowed to discover different molecular subtypes of TNBC (i. e., basal-like, claudin-low), demonstrated the presence of «immune-activated» subtypes with better disease outcome. In addition, further studies have characterized molecular features characteristic of TNBC, including a high rates of TP53 mutations, MEK and PI3K pathway activation, loss RB1 protein function, genetic similarities to serous ovarian cancers, including inactivation of BRCA pathway. Understanding of the genetic heterogeneity of TNBC led to promising therapeutic approaches, including DNA-damaging agents (i. e., platinum salts and PARP inhibitors) and immunotherapy currently. Platinum  salts became a standard component in the chemotherapy regimens for patients with metastatic TNBC. The best outcomes are observed among patients with BRCA-mutation. Furthermore, the use of platinum salts in neoadjuvant regimens showes higher pathologic complete response rates. The presence of tumor infiltrating lymphocytes in TNBC carries prognostic role. The use of checkpoint inhibitors, including PD‑1 and PD-L1 inhibitors, actively investigated in the setting of metastatic TNBC. For oncologists it’s very important to have ability to assign the optimal therapeutics regimens, based on knowledge of the heterogeneity of TNBC, that would led to improve patient outcome.

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The authors declare that there are no conflicts of interest present.