Abstract A146: Preclinical models relevant to the treatment of post-menopausal breast cancer.

The past decades have witnessed immense progress in the treatment of hormone-sensitive breast cancer. However, despite the success of agents targeting estrogen activity, a significant proportion of patients will experience relapse due to endocrine therapy resistance. In order to better understand the underlying causes and enable successful targeting of implicated pathways, preclinical models that recapitulate the post-menopausal setting are essential. To this end, we have developed a panel of estrogen receptor (ER+) models with varying senstivity to endocrine therapies. Our panel includes models of long-term estrogen-deprivation (LTED), a surrogate for longterm exposure and relapse on aromatase inhibitors. Using both xenograft (MCF7LTED, HCC1428LTED) and primary tumor models (BR0555fLTED and CTC-174LTED), we have utilized them to benchmark standard of care treatments and test the efficacy of novel agents. Importantly, we demonstrate that these models closely mimick the post-menopausal hormonal millieu found in patients and recapitulate pharmacodynamic responses observed in the clinic. As such, these are instrumental tools to uncovering endocrine resistance mechanisms and provide a potentially predictive platform for clinical efficacy. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A146. Citation Format: Ermira Pazolli, Anne Marie Mazzola, Jon Curwen, Hazel Weir, Casey Kiessel, Michael Grondine, Celina D'Cruz, Mike Zinda. Preclinical models relevant to the treatment of post-menopausal breast cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A146.