Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer.

ABSTRACT:

Background

Endocrine therapy remains the mainstay of treatment for estrogen receptor-positive (ER+) breast cancer. Constitutively active mutations in the ligand binding domain of ERα render tumors resistant to endocrine agents. Breast cancers with the two most common ERα mutations, Y537S and D538G, have low sensitivity to fulvestrant inhibition, a typical second-line endocrine therapy. Lasofoxifene is a selective estrogen receptor modulator with benefits on bone health and breast cancer prevention potential. This study investigated the anti-tumor activity of lasofoxifene in breast cancer xenografts expressing Y537S and D538G ERα mutants. The combination of lasofoxifene with palbociclib, a CDK4/6 inhibitor, was also evaluated.

Methods

Luciferase-GFP tagged MCF7 cells bearing

SUBMITTER: Laine M 

PROVIDER: S-EPMC8117302 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature