posters International Association for Breast Cancer Research 2014

Targeting the nuclear receptor superfamily for treatment and prognosis in breast cancer (#30)

Dinny Graham 1 , Peter J. Fuller 2 , John W. Funder 2 , Evan R. Simpson 2 , Peter J. Leedman 3 , Wayne D. Tilley 4 , George E.O. Muscat 5 , Christine L. Clarke 1
  1. University of Sydney at the Westmead Millennium Institute, Westmead, NSW, Australia
  2. Prince Henry’s Institute of Medical Research, Clayton, VIC, Australia
  3. Laboratory for Cancer Medicine, Centre for Medical Research, Western Australian Institute for Medical Research and School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
  4. Dame Roma Mitchell Cancer Research Laboratories, Hanson Institute, University of Adelaide, Adelaide, SA, Australia
  5. Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia

It is well established that breast cancer is a hormone-dependent disease. Treatments that target the estrogen receptor (ER) signalling pathway, represent standard of care for the 70% of cases in which ER is expressed. Moreover, tumour expression of ER and progesterone receptor (PR) is a favourable marker of disease outcome, and ER+/PR+ cancers are generally better differentiated and slower growing. However, tumours that lack ER and PR generally fail to respond to hormonal treatment. Moreover, approximately one quarter of ER+ cancers will recur within 10 years, due to the development of treatment resistance and emergence of ER- disease. ER and PR are members of a large family of related transcription factors whose influence spans every aspect of normal human physiology. Expression of several NRs is altered in breast cancer, and subgroups of NRs are associated with histologic grade and predict metastasis-free survival in ER+ disease. The existence of ligands for many of these NRs, which are often approved for therapeutic use in other settings, creates a compelling argument for their further exploration as potential treatment targets in breast cancer. We measured protein expression of 10 NRs, which we previously identified as altered in breast cancer at the transcript level, in a cohort of 45 breast tissues (15 normal, 15 ER+, 15ER- breast cancers) and correlated intensity and positivity with tissue type, ER status and tumour grade. Protein levels of six NRs were significantly altered in cancer relative to normal tissue. Moreover, there was a consistent inverse relationship between NR expression and grade that was specific to ER- cases, suggesting that these NRs may together predict outcome in this subgroup. Our data demonstrate the utility of NRs in defining subsets of breast cancer and suggest potential treatment targets in cases where ER-targeted treatments are not effective.