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Эволюция представлений о тройном негативном раке молочной железы: от биологии опухоли к современному лекарственному лечению

https://doi.org/10.18027/2224-5057-2017-1-5-17

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Аннотация

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.

Об авторах

О. В. СМИРНОВА
Московский государственный медико-стоматологический университет им. А.И. Евдокимова, Онкологический Клинический Диспансер № 1
Россия
аспирант 3 года обучения ,онкологии и лучевой терапии,  врач-онколог химиотерапевтического отделения стационара


В. Е. БОРИСОВ
Онкологический Клинический Диспансер № 1
Россия
д.м.н., профессор, зав. отделением амбулаторной химиотерапии с дневным стационаром


Г. П. ГЕНС
Московский государственный медико-стоматологический университет им. А.И. Евдокимова
Россия
д.м.н., доцент кафедры онкологии и лучевой терапии


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Для цитирования:


СМИРНОВА О.В., БОРИСОВ В.Е., ГЕНС Г.П. Эволюция представлений о тройном негативном раке молочной железы: от биологии опухоли к современному лекарственному лечению. Злокачественные опухоли. 2017;(1):5-17. https://doi.org/10.18027/2224-5057-2017-1-5-17

For citation:


SMIRNOVA O.V., BORISOV V.I., GENS G.P. The evolution of knowledge of triple-negative breast cancer: from biology to novel drug treatment. Malignant tumours. 2017;(1):5-17. (In Russ.) https://doi.org/10.18027/2224-5057-2017-1-5-17

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ISSN 2224-5057 (Print)
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