Metastatik Triple Negatif Meme Kanserinde Sistemik Tedavi
Özet
Meme kanseri, dünya genelinde kadınlarda en sık görülen malignite olup, triple negatif alt tip tüm olguların yaklaşık %15-20’sini oluşturur. Hormon reseptörleri (ER/PR) ve HER2 proteini ekspresyonu bulunmayan TNMK, yüksek proliferasyon oranı, erken metastaz eğilimi ve kötü prognozuyla dikkat çeker. Özellikle visseral organ metastazı sıklığı ve düşük sağkalım oranları, bu hasta grubunda tedavi yönetimini zorlaştırmaktadır. Son yıllarda TNMK’ de yapılan çalışmalar sonucunda standart sistemik kemoterapi dışında da immunoterapi, antikor-ilaç konjugatları, PARP inhibitörleri güncel tedavi seçenekleri içerisinde yerini almıştır. TNMK’ de tedavi stratejisinin belirlenmesinde genel hatlarıyla visseral kriz durumu, PD-L1 ekspresyonu ve germline BRCA1/2 mutasyon varlığı temel belirleyicilerdir. PD-L1 pozitif hastalarda kemoterapiyle birlikte pembrolizumab eklenmesi progresyonsuz ve genel sağkalımı uzatırken, BRCA mutasyonu taşıyan hastalarda PARP inhibitörleri (olaparib, talazoparib) etkili tedavi seçenekleri sunmaktadır. PD-L1 negatif ve BRCA mutasyonu olmayan olgularda ise taksan veya platin bazlı tek ajan kemoterapi genellikle ilk tercih olmaktadır. İleri basamak tedavilerde Trop-2 hedefli antikor-ilaç konjugatı sakituzumab govitekan ve HER2-low alt grupta fam-trastuzumab-derukstekan anlamlı klinik fayda sağlamıştır. Ayrıca MSI-H, TMB-H, NTRK veya RET pozitif hastalarda immün ve hedefe yönelik tedaviler umut verici sonuçlar göstermektedir. Bu gelişmeler, TNMK’de kişiselleştirilmiş tedavi yaklaşımlarının ve moleküler hedeflerin gelecekte daha da önem kazanacağını ortaya koymaktadır.
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