Aromatase inhibitors decrease radiation-induced lung fibrosis: Results of an experimental study.
OBJECTIVE
In 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.


METHODS
60 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.


RESULTS
Mean 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.


CONCLUSIONS
In this study, we found that AI decreased RT-induced lung fibrosis to the control group level suggesting protective effect.
Department of Radiation Oncology, Medipol University, Medical School, TEM Avrupa Otoyolu Goztepe cikisi, No:1 Bagcilar, Istanbul, Turkey. Electronic address: ayseyildirimaltinok@gmail.com.
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Altinok
Department of Pathology, GATA Haydarpasa Training Hospital Selimiye Mh., Tibbiye Cd., 34668, Uskudar, Istanbul, Turkey. Electronic address: syildirim@gata.edu.tr.
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Yildirim
Department of Experimental Animal Breeding and Research Laboratory, Cerrahpasa Medical School, Istanbul University, Turkey.
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Altug
Department of Biostatistics, Trakya University, Medical School Balkan Yerleskesi, 22030, Edirne, Turkey. Electronic address: nsut@trakya.edu.tr.
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Department of Radiation Oncology Cerrahpasa Medical School, Istanbul University Cerrah Pasa Mh., Cerrahpasa Tıp Fk., No:53, 34098 Fatih/Istanbul, Istanbul, Turkey. Electronic address: aober@superonline.com.
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Ober
Department of Radiation Oncology, CHUV,CH-1011, Lausanne Rue du Bugnon 46, 1011, Lausanne, Switzerland. Electronic address: mahmut.ozsahin@chuv.ch.
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Ozsahin
Department of Radiation Oncology, CRLC Val d'Aurelle, 31, Rue Croix Verte, 34000, Montpellier, France. Electronic address: David.Azria@valdorel.fnclcc.fr.
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Azria
Department of Radiation Oncology Cerrahpasa Medical School, Istanbul University Cerrah Pasa Mh., Cerrahpasa Tıp Fk., No:53, 34098 Fatih/Istanbul, Istanbul, Turkey. Electronic address: nuranbese@superonline.com.
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Bese
D000077384:Anastrozole; D000730:Androstadienes / Q000627:therapeutic use*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005260:Female; D000077289:Letrozole; D009570:Nitriles / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use*
D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; D000077289:Letrozole; C056516:exemestane
Aromatase inhibitors; Breast cancer; Radiation therapy; Radioprotective effect