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Abstract Estrogen receptor (ER) signaling is the main driver of tumorigenesis in ER+ breast cancers by inducing proliferation and survival through genomic and non-genomic means, therefore inhibition of ER signaling has been a mainstay of treatment for decades. Roughly 30 percent of patients will develop treatment-refractory recurrence or metastasis within their lifetime, which may include metastasis to the bone, lung, liver, and brain. Although advances in treatment approaches have prolonged average progression free survival, metastatic breast cancer remains incurable. A new endocrine therapy, Elacestrant, has been approved by the FDA for the treatment of ER+, ESR1-mutant advanced or metastatic breast cancer. The mechanism of action of Elacestrant involves both degradation of ER and modulation of ER signaling through non-degradative means. The central hypothesis of this study was that Elacestrant may prolong progression free survival in animal models of breast to bone metastasis, because modulation of ER in the bone would decrease the incidence of osteoporosis which is induced by other endocrine therapies. However, we discovered that prolonged Elacestrant treatment induces destruction of the trabecular bone structure and increased adipocyte mass within the bone, consistent with an osteoporotic phenotype. Ongoing studies will seek to determine if other endocrine therapies will provide better protection to the bone architecture while reducing metastatic burden in animal models. Additionally, we will evaluate organotropic efficacy of new endocrine therapies on multi-organ metastasis to determine if utility is contingent upon the metastatic site. Citation Format: Emily Kate Zboril, Julia E. Altman, Nicole S. Hairr, Rachel K. Myrick, Amy L. Olex, Mikhail G. Dozmorov, J. Chuck Harrell. Assessment of new generation endocrine therapies for the treatment of breast to bone metastasis abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 6269.
Zboril et al. (2024) studied this question.