Pushing estrogen receptor around in breast cancer

    1. Carlo Palmieri3,*
    1. 1Garvan Institute of Medical Research and St Vincent’s Hospital, University of New South Wales, Sydney, New South Wales, Australia
    2. 2Dame Roma Mitchell Cancer Research Laboratories and Adelaide Prostate Cancer Research Centre, University of Adelaide, Adelaide, South Australia, Australia
    3. 3Institute of Translational Medicine, University of Liverpool, Clatterbridge Cancer Centre, NHS Foundation Trust, and Royal Liverpool University Hospital, Liverpool, Merseyside, UK
    1. Correspondence should be addressed to W D Tilley or C Palmieri; Email: wayne.tilley{at}adelaide.edu.au or c.palmieri{at}liverpool.ac.uk


    The estrogen receptor-α (herein called ER) is a nuclear sex steroid receptor (SSR) that is expressed in approximately 75% of breast cancers. Therapies that modulate ER action have substantially improved the survival of patients with ER-positive breast cancer, but resistance to treatment still remains a major clinical problem. Treating resistant breast cancer requires co-targeting of ER and alternate signalling pathways that contribute to resistance to improve the efficacy and benefit of currently available treatments. Emerging data have shown that other SSRs may regulate the sites at which ER binds to DNA in ways that can powerfully suppress the oncogenic activity of ER in breast cancer. This includes the progesterone receptor (PR) that was recently shown to reprogram the ER DNA binding landscape towards genes associated with a favourable outcome. Another attractive candidate is the androgen receptor (AR), which is expressed in the majority of breast cancers and inhibits growth of the normal breast and ER-positive tumours when activated by ligand. These findings have led to the initiation of breast cancer clinical trials evaluating therapies that selectively harness the ability of SSRs to ‘push’ ER towards anti-tumorigenic activity. Our review will focus on the established and emerging clinical evidence for activating PR or AR in ER-positive breast cancer to inhibit the tumour growth-promoting functions of ER.

    • Received 6 October 2016
    • Accepted 11 October 2016
    • Made available online as an Accepted Preprint 11 October 2016
    | Table of Contents