Estrogen receptor-positive (ER+) breast cancer can undergo metastatic spread to the brain, which occurs in up to 15% of HER2-/ER+ metastatic breast cancer patients. Although endocrine therapy is not explicitly approved for brain metastasis and clinical trials are lacking, anecdotal reports of clinical responses by endocrine agents motivate further investigation. One such agent is the ER antagonist tamoxifen, which has previously been shown to reach high levels in brain tissue and ER+ brain metastases in patients with breast cancer*. We previously reported that OP-1250, a novel, oral complete ER antagonist (CERAN), penetrates the brain and is efficacious at shrinking tumors in a xenograft brain metastasis model in which patient derived human ER+ tumors were intracranially transplanted into immunocompromised mice**. Here we compare the ability of OP-1250 to shrink brain tumors in this model with tamoxifen and other agents. Whereas tamoxifen indeed had therapeutic effects in this brain xenograft model, the effect was not as profound as that of OP-1250, which was able to completely clear the tumors in many animals, as determined by MRI.

* Lien et al. Distribution of tamoxifen and metabolites into brain tissue and brain metastases in breast cancer patients. Br. J. Cancer, 1991, 63, 641-645.**Hodges-Gallagher, et al. OP-1250 a complete estrogen receptor antagonist that penetrates the brain and prevents lethality from an intracranial xenograft tumors expressing mutant ESR1, abstract, AACR 2020

Citation Format: Leslie Hodges-Gallagher, Alison D. Parisian, Richard Sun, David C. Myles, Pamela M. Klein, Cyrus L. Harmon, Peter J. Kushner. The complete estrogen receptor antagonist (CERAN) OP-1250 shrinks ER+ brain metastases in an intracranial xenograft tumor model expressing mutant ESR1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB122.