Fig. 2

Anti-estrogen and radiation in combination slows the growth of TC11 ER+ mammary tumors. A Schematic of treatment timeline. FVB/N mice with TC11 tumors in the caudal mammary fat pads received weekly treatments with fulvestrant (Fulv) or oil control, initiated 3 weeks after transplantation as in Fig. 1, and/or 3 doses of RT (8 Gy administered on days 6, 7, and 8 following initiation of Fulv or oil treatments). B Tumor size was measured biweekly (mean ± SEM, n = 6 for single treatments, n = 9 for RT+Fulv). C Comparison of mammary tumor volumes in animals receiving RT and RT+Fulv on day 46 after transplantation, the last time when animals in all treatment groups were still alive. Differences among treatments were determined by one way ANOVA, followed by Tukey post tests, *, p < 0.05; **, p < 0.01; ***, p < 0.001. D Comparison of mammary tumor volumes in animals receiving RT and RT+Fulv on day 53 after transplantation, the last time when the RT-treated group was alive. Unpaired t test, *, p < 0.05. E Tumor growth curves in individual mice shown in (B). F Kaplan Meier analysis of survival (log-rank tests, **, p < 0.01; ****; p < 0.0001). G Fulvestrant does not affect the clonogenic response to RT in TC11 cells in vitro. 24 h after plating, TC11 cells were treated ± Fulv for 24 h, followed by a single dose of increasing RT (0–8 Gy). Clonogenic analyses were performed as described in the Materials and Methods. H Fulvestrant does not alter the type I IFN response following RT in vitro, which has been reported to occur downstream of cGAS/STING activation, but this treatment strongly reduces transcripts for Greb1, a well characterized estrogen target gene. TC11 cells were treated ± 8 Gy RT, ± Fulv for the times shown, and transcripts analyzed by qPCR as described in the Materials and Methods. Differences among treatments were determined by one way ANOVA, followed by Tukey post tests (*, p < 0.05; **, p < 0.01)