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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.

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