The Effects of Hormonotherapy Following Concomitant Use of Trastuzumab and Radiation Therapy on Late Skin Toxicity

Abstract

To investigate whether hormonotherapy followed by concomitant use of trastuzumab (T) and radiation therapy (RT) contributes to the development of radiation-induced skin fibrosis. 70 healthy female rats divided into seven groups: Control group (C) underwent no procedure. RT group underwent thoracic radiation (TR). T group was administered T. T+RT+Tx group was administered concomitant T and TR, followed by tamoxifen. T+RT+Le group was administered concomitant T and TR, followed by letrozole. T+RT+An group was administered concomitant T and TR, followed by anastrazole. T+RT+Ex group was administered concomitant T and TR, followed by exemestane. Trastuzumab was administered in 6 mg/kg. TR was performed two hours after T administration. Hormonotherapy was given at one week following RT. Rats were sacrificed at 24 weeks. Skin was scored in histopathological examination. Skin inflammation was most commonly seen in the RT, T+RT+Tx and T+RT+Le group. Skin fibrosis was present in all subjects exposed to RT. Control group, T and T+RT+Ex group had the lowest vascular damage scores, while RT, T+RT+Tx and T+RT+Le had the highest scores. The RT, T+RT+Tx and T+RT+Le group had the highest muscular fibrosis scores. Muscular fibrosis was lesser in T+RT+An and T+RT+Ex group. The rate of vascular damage in muscular tissue was the highest in RT, T+RT+Tx and T+RT+Le group. No vascular damage was observed in T and T+RT+Ex group. Our study results suggested that tamoxifen and letrozole following concomitant use of T and RT increased skin fibrosis, while anastrazole and exemestane reduced radiation-induced skin fibrosis.Key Words: Skin, Fibrosis, Radiation therapy,Trastuzumab, Hormonotherapy ÖZET Radyoterapi ile Eşzamanlı Trastuzumab Tedavisinden Sonra Verilen Hormonoterapinin Ciltte Gelişen Geç Toksisite Üzerine EtkisiRadyoterapi ile eşzamanlı trastuzumab tedavisinden sonra verilen hormonoterapinin ciltte radyasyon fibrozisi gelişimine katkısı olup olmayacağını araştırmaktır. 70 adet erişkin sağlıklı sıçan, 7 gruba ayrıldı. K grup (Kontrol grubu); RT grubu (Sadece radyoterapi uygulanan); T grubu (Sadece trastuzumab verilen); T+RT+Tam grubu (RT ile eş zamanlı T verildikten sonra tamoksifen verilen grup); T+RT+Le grubu (RT ile eş zamanlı T sonrası letrozol verilen); T+RT+An grubu (RT ile eş zamanlı T sonrası anastrazol verilen); T+RT+Ex grubu (RT ile eşzamanlı T sonrası exemestan) verilen grup olarak belirlendi. Trastuzumab, 6 mg/kg verildi. RT, T'den iki saat sonra, göğüs duvarına tek fraksiyonda ışınlama yapıldı. RT'den bir hafta sonra hormonoterapi ilaçları 6 ay süre ile verildi. 24 hafta sonra sıçanlar sakrifiye edildi. Deri dokusu histopatolojik olarak incelendi. Deride inflemasyon en fazla RT, T+RT+Tam ve T+RT+Le gruplarında görüldü. RT alan grupların hepsinde deride fibrosizin oluştuğu görüldü. Deride vasküler hasar skorlaması en düşük kontrol, T ve T+RT+Ex gruplarında en yüksek skorlama RT, T+RT+Tam ve T+RT+Le gruplarında bulundu. Kasta fibrosiz skorlaması en yüksek RT, T, T+RT+Tam, T+RT+Le gruplarında bulundu. T+RT+An and...