Triple Negatif Meme Kanserinde Neoadjuvan Tedavi Yaklaşımları
Özet
TNMK, östrojen, progesteron ve HER2 reseptörlerinden yoksun olup tüm meme kanserlerinin yaklaşık %15-20’sini oluşturur. BRCA1 mutasyonu taşıyan olgularda sık görülür ve agresif seyirlidir. Neoadjuvan tedavi, tümör boyutunu küçültmek, meme koruyucu cerrahiyi mümkün kılmak ve patolojik tam yanıt (pCR) oranını değerlendirmek amacıyla uygulanır. Endikasyonlar arasında lokal ileri hastalık (evre III, T3-T4), klinik nod pozitif olgular ve cerrahiye geçici kontrendikasyon durumları yer alır. Tedavi öncesinde biyopsiyle tümör biyolojisi belirlenir, lezyon klipslenir ve evreleme için uygun görüntüleme yapılır. Standart neoadjuvan protokoller antrasiklin-taxan kombinasyonlarıdır. Platin ajanlar (özellikle karboplatin), BRCA mutasyonu veya homolog rekombinasyon yetmezliği bulunan olgularda pCR oranlarını artırır; ancak sağkalım üzerindeki katkısı sınırlıdır. PARP inhibitörleri (ör. veliparib) platin temelli kemoterapiye eklenmiş ancak ek fayda sınırlı kalmıştır. İmmünoterapi, son yıllarda tedavinin temel unsuru hâline gelmiştir. KEYNOTE-522 çalışması ile pembrolizumab, pCR oranını %65’e çıkararak FDA onayı almıştır. IMpassion031 (atezolizumab) ve GeparNUEVO (durvalumab) çalışmaları da immünoterapinin pCR ve sağkalımda anlamlı iyileşmeler sağladığını göstermiştir. Sonuçta TNMK’de neoadjuvan tedavi stratejileri, klasik kemoterapiden moleküler ve immün hedefli yaklaşımlara evrilmiş; kişiselleştirilmiş tedavi, biyobelirteç temelli seçim ve uzun dönem sağkalımda belirgin ilerleme sağlamıştır.
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