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Aromatase inhibitors decrease radiation-induced lung fibrosis: Results of an experimental study
Affiliation:1. Department of Radiation Oncology, Medipol University, Medical School, TEM Avrupa Otoyolu Goztepe cikisi, No:1 Bagcilar, Istanbul, Turkey;2. Department of Pathology, GATA Haydarpasa Training Hospital Selimiye Mh., Tibbiye Cd., 34668, Uskudar, Istanbul, Turkey;3. Department of Experimental Animal Breeding and Research Laboratory, Cerrahpasa Medical School, Istanbul University, Turkey;4. Department of Biostatistics, Trakya University, Medical School Balkan Yerleskesi, 22030, Edirne, Turkey;5. Department of Radiation Oncology Cerrahpasa Medical School, Istanbul University Cerrah Pasa Mh., Cerrahpasa Tıp Fk., No:53, 34098 Fatih/Istanbul, Istanbul, Turkey;6. Department of Radiation Oncology, CHUV,CH-1011, Lausanne Rue du Bugnon 46, 1011, Lausanne, Switzerland;7. Department of Radiation Oncology, CRLC Val d''Aurelle, 31, Rue Croix Verte, 34000, Montpellier, France;1. Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China;2. Department of Pathology, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China;1. University of Iowa Holden Comprehensive Cancer Center, Iowa City, IA, USA;2. Grupo Oncológico Cooperativo del Sur (GOCS), Argentina;3. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina;1. Department of Microwave Safety, Military Institute of Hygiene and Epidemiology, Kozielska 4, PL 01-163, Warszawa, Poland;2. Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, PL 02-091, Warszawa, Poland;3. Department of Pharmacology and Toxicology, Military Institute of Hygiene and Epidemiology, Kozielska 4, PL 01-163, Warszawa, Poland;4. Pathology Department, Center for Biostructure Research, Warsaw Medical University, Chałubińskiego 5, PL 02-004 Warszawa, Poland;5. Pediatric Clinic, Nefrology and Allergology Department, Military Medical Institute, Szaserów 128, PL 04-141, Warszawa, Poland
Abstract:PurposeIn experimental and clinical trials, tamoxifen (TAM) has been shown to increase radiation-induced lung fibrosis (RILF). Furthermore, aromatase inhibitors (AI) have been shown to be superior to TAM in the adjuvant setting and preclinical data suggest that letrozole (LET) sensitizes breast cancer cells to ionizing radiation in other studies. In this experimental study, we evaluated whether AI have any impact on the development of RILF in rats.Materials and methods60 female wistar- albino rats were divided into 6 groups: Control (group A), RT alone (group B), RT + TAM (group C), RT + anastrozole (ANA group D), RT + LET (group E), and RT + exemestane (EXE, group F). RT consisted of 30 Gy in 10 fractions to both lungs with an anterior field at 2 cm depth. Equivalent doses for 60 kg adult dose per day of TAM, ANA, LET, and EXE were calculated according to the mean weight of rats and orally administrated with a feeding tube. Percentage of lung with fibrosis was quantified with image analysis of histological sections of the lung. The mean score values were calculated for each group. the significance of the differences among groups were calculated using one way ANOVA test and Tukey HSD post-hoc test.ResultsMean values of fibrosis were 1.7, 5.9, 6.7, 2.5, 2 and 2.2 for groups A, B, C, D, E, and F, respectively (p = 0.000). TAM increased RT-induced lung fibrosis but without statistical significance. Groups treated with RT + AI showed significantly less lung fibrosis than groups treated with RT alone or RT + TAM (p = 0.000). RT + AI groups showed nearly similar RT-induced lung fibrosis than control group.ConclusionsIn this study, we found that AI decreased RT-induced lung fibrosis to the control group level suggesting protective effect.
Keywords:Aromatase inhibitors  Radiation therapy  Radioprotective effect  Breast cancer
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