ESTRO 2021 Abstract Book

S341

ESTRO 2021

Results In both ER positive (MCF7, T47D) and ER negative (MDA-MB231) breast cancer cells, levels of 5 uM of 4OHT induced ROS production (Fig. 1A). DNA damage increased with 4OHT as evidenced by 53BP1 foci (Fig. 1B) and an accumulating number of micronuclei (Fig. 1C). DNA damage and micronuclei both represent targets of cGAS, whose expression indeed increased in cells treated with 4OHT (Fig. 1D). STING inhibition decreased the acute induction of IFN stimulated genes (IFI27, OAS1, DDX60). Furthermore, pronounced effects were found on mitochondria, including elevated expression of mitochondrial complex 1 subunit NDUFS3 and PINK1, as a marker for mitophagy (Fig. 1E). In patients treated neo-adjuvantly with tamoxifen, an induction of NfKB and TNFa-associated genes was described (Kastrati et al. 2020). By additional pathway analyses we show significant activation of pathways involved in responses to ROS (Fig. 2), indicating clinical relevance.

Conclusion In conclusion, we show an induction of ROS signaling by 4-hydroxy-tamoxifen leading to DNA damage and micronuclei formation as targets of the DNA sensor cGAS which in turn could initiate a STING-IFN pathway response, which is known to be involved in radioresistance.

Poster highlights: Poster highlights 17: Gynaecological

PH-0442 Risk of recurrence identified by MRI and FDG-PET in locally advanced cervical cancer patients K. Skipar 1 , T. Hompland 1 , K.V. Lund 2 , E.S. Nakken 3 , K. Bruheim 3 , H. Lyng 4 1 Oslo University Hospital, The Norwegian Radium Hospital, Department of Radiation Biology, Oslo, Norway; 2 Oslo University Hospital, The Norwegian Hospital, Department of Radiology and Nuclear Medicine, Oslo, Norway; 3 Oslo University Hospital, The Norwegian Hospital, Department of Oncology, Oslo, Norway; 4 Oslo