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Purpose: It is now well known that evading apoptosis, as a cancer hallmark, can lead to tumour initiation, progression and metastasis. As a result of genome wide association studies, an initiator protease in this pathway, caspase 8 (CASP8), has been found to be an important gene regarding breast cancer susceptibility. The alterations of the expression of this gene have been reported in breast cancer cell lines. Given that in previous studies expression analysis of this gene had only been done in breast cancer cell lines, in this study we aimed to evaluate the expression of this gene in breast cancer tissues versus adjacent normal tissues, using real-time quantitative method., Methods: Caspase 8 mRNA expression was quantified using comparative RT-qPCR in 27 fresh frozen breast tumours and 27 adjacent normal tissues. Moreover, relationship between the expression changes of CASP8 in tumour tissue and various clinical and pathological features were evaluated in an Iranian population., Results: The present study showed that expression of CASP8 was significantly reduced in tumour tissues compared to neighbouring normal tissues (p = .004). CASP8 expression was significantly correlated with the status of hormone receptors (ER and PR)., Conclusion: To the best of our knowledge, this study is the first report on reduced expression of CASP8 in breast cancer versus adjacent normal tissues. Our data support previous results obtained from cell lines and therefore highlights the seminal role of the induction of CASP8 expression, as a novel therapeutic approach, in order to sensitize tumour cells to apoptotic stimuli., (Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.)