Aromataz İnhibitörleri
Özet
Aromataz inhibitörleri (Aİ), postmenopozal kadınlarda östrojen sentezinin son adımını katalize eden aromataz enzimini bloke ederek hormon reseptörü pozitif meme kanserinin tedavisinde standart bir yaklaşım sunmaktadır. Klinik kullanımda yer alan anastrozol, letrozol ve eksemestan; steroidal (geri dönüşsüz) ve steroidal olmayan (yarışmalı) olmak üzere ikiye ayrılır. Yapılan çok merkezli faz III çalışmalar ve geniş kapsamlı meta-analizler, Aİ’lerin hem başlangıç tedavisinde hem de tamoksifenden sonraki ardışık kullanımda hastalıksız sağkalımı (HS) ve meme kanserine bağlı ölüm riskini tamoksifene kıyasla anlamlı derecede iyileştirdiğini göstermiştir. İlaçların neoadjuvan ve uzatılmış adjuvan ortamlarda da etkili olduğu kanıtlanmıştır. Genel olarak iyi tolere edilen bu ajanlar, tamoksifene göre daha düşük endometriyal kanser ve tromboembolizm riski taşırken, kas-iskelet sistemi semptomlarını, osteoporozu ve kemik kırığı oranını belirgin şekilde artırır. Bu nedenle tedavi sürecinde kemik yoğunluğu takibi ve proflaktik bisfosfonat kullanımı önerilmektedir.
Aromatase inhibitors (AIs) provide a standard treatment approach for hormone receptor-positive breast cancer in postmenopausal women by blocking the aromatase enzyme, which catalyzes the final step of estrogen biosynthesis. The current clinical agents, including anastrozole, letrozole, and exemestane, are classified into steroidal (irreversible) and non-steroidal (competitive) inhibitors. Multiple phase III trials and large-scale meta-analyses have demonstrated that AIs significantly improve disease-free survival (DFS) and reduce the risk of breast cancer-related mortality compared to tamoxifen, both as initial therapy and in sequential strategies following tamoxifen. Additionally, these agents have proven effective in neoadjuvant and extended adjuvant settings. While AIs are generally well-tolerated and carry a lower risk of endometrial cancer and thromboembolism than tamoxifen, they markedly increase musculoskeletal symptoms, osteopenia, osteoporosis, and bone fracture rates. Consequently, regular monitoring of bone mineral density and prophylactic bisphosphonate therapy are strongly recommended during the treatment period.
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