Эволюция представлений о тройном негативном раке молочной железы: от биологии опухоли к современному лекарственному лечению
Автор: Смирнова Ольга Владимировна, Борисов Василий Иванович, Генс Гелена Петровна
Журнал: Злокачественные опухоли @malignanttumors
Рубрика: Фундаментальная онкология и экспериментальная медицина
Статья в выпуске: 1 (22), 2017 года.
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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.
Тройной негативный рак молочной железы, метастазы, химиотерапия, иммунотерапия
Короткий адрес: https://sciup.org/140223025
IDR: 140223025 | DOI: 10.18027/2224-5057-2017-1-5-17
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