Abstract P5-01-11: Nonclinical activity of fulvestrant in a panel of ER+ breast XPDX models representing clinically acquired and innate resistance to endocrine therapies

作者：April B. Cabang, Crystal Moreno, Johnnie R Flores, Jenna Boedeker, Alyssa Simonson, Jun Ma, Amy Lang, Gladys Rodriguez, Arthur Rosenthal, Kyriakos P. Papadopoulos, Amita Patnaik, Drew Rasco, Lon Smith, M. Beeram, Ronald Drengler, Luis Rodriguez, Steven Abbate, Scott Ulmer, Michael J. Wick · 发表于：Cancer Research · 年份：2022 · DOI：10.1158/1538-7445.sabcs21-p5-01-11 · 研究领域：Estrogen and related hormone effects、Advanced Breast Cancer Therapies、HER2/EGFR in Cancer Research

Abstract Background: Fulvestrant is a selective estrogen receptor modulator (SERM) approved as a single agent for estrogen receptor positive, HER2 negative breast cancer patients at various stages of disease and in combination with CDK4/6 inhibitors following endocrine therapy failure. Although this agent requires intramuscular injection, it has demonstrated superior activity and fewer side effects versus some oral endocrine treatments however, resistance to fulvestrant often develops. To better understand fulvestrant resistance and its utility in patients who have failed other endocrine therapies, we evaluated the agent in a panel of ER+ breast models established from patients at various stages of disease representing endocrine-sensitive and -resistant disease. Methods: Sixty-five previously developed ER+ breast XPDX models were evaluated in this study. Models were grown subcutaneously in female athymic nude mice supplemented with estradiol in drinking water when necessary. All models were characterized at early and late passages for estrogen receptor expression by immunohistochemistry and profiled using WES and RNAseq. For in vivo studies, fulvestrant was administered by subcutaneous injection at 2.5 or 5 mg per dose once weekly until study completion. In vivo study endpoints included tumor volume and time from treatment initiation with %T/C values and tumor regression reported at study completion; a %T/C of ≤ 20 versus control was considered sensitive. Tumor regression (%T...