Abstract 3302: Subtype-specific radiation response in a mouse model of human breast cancer

Abstract

Abstract Radiation therapy is an important component of multimodal treatment for women with breast cancer. However, breast radiotherapy is currently delivered uniformly, regardless of breast cancer subtype. Recent clinical data have suggested that different subtypes of breast cancer may respond differently to radiation. Understanding the intrinsic variation of radiation response in breast cancer subtypes would lay the foundation for individualized radiotherapy designed to limit toxicity in those with radiation responsive cancers. Furthermore, identification of molecular targets can be used to modulate treatment outcomes in patients with radiation resistant tumors. Our previous in vitro studies have identified an association between breast cancer subtype and gene expression profiles in response to radiation in breast tumor cell lines. Cell lines with the greatest response to radiation were luminal subtype and exhibited preferential induction of genes involved in programmed cell death, such as FAS. In this study, we investigated tumor growth and FAS induction in response to radiation in a mouse model of breast cancer. MCF7 (luminal) or SUM159 (basal) cells were implanted orthotopically into the dorsal mammary fat pad of athymic nude mice. These mice were then treated with different doses of radiation. Our results showed that radiation treatment inhibited MCF7 tumor growth in a dose-dependent manner, while radiation treatment had little effect on SUM159 tumor growth. In addition, FAS was induced in MCF7 tumors 24 hour after radiation, but there was no change in FAS expression in SUM159 tumors. However, injection of FAS-stimulating antibody intratumorally led to downstream caspase 8 and PARP activation, suggesting that the FAS signaling pathway remains intact and can be used to modulate radiation response in the resistant SUM159 cells. In conclusion, these results suggest that there is intrinsic variation in radiation response among breast cancer subtypes and that stimulation of FAS may have the potential to modulate radiation response. Citation Format: Chen-Ting Lee, Yingchun Zhou, Sharareh Siamakpour-Reihani, Kingshuk R. Choudhury, Mark W. Dewhirst, Janet K. Horton. Subtype-specific radiation response in a mouse model of human breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3302. doi:10.1158/1538-7445.AM2015-3302