Poster Presentation Women's Health Forum 2021

Androgens antagonise the promotional effect of oestrogen on the mammographic density of patient-derived explants of human breast tissue (#28)

Xuan Huang 1 , Gina Reye 1 , Konstantin I Momot 2 , Tony Blick 1 , Thomas Llloyd 3 , Wayne D Tilley 4 , Theresa E Hickey 4 , Cameron E Snell 5 , Erik (Rik) W Thompson 1 , Honor J Hugo 6
  1. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
  2. Chemistry and Physics, Queensland University of Technology, Brisbane, QLD, Australia
  3. Radiology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
  4. Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, QLD, Australia
  5. Mater Pathology, Mater Hospital Brisbane, South Brisbane, QLD, Australia
  6. The University of the Sunshine Coast, Sippy Downs, QLD, Australia

Increased mammographic density (MD) is a strong and independent risk factor for breast cancer. Lifetime estrogenic exposure is associated with increased MD, whereas androgen hormonal activity has been shown to inhibit proliferation of breast epithelial cells and be protective in oestrogen receptor (ER) - positive breast cancer. The androgenic effects on MD have not been widely investigated. We studied the effect of 17β-oestradiol (E2) alone or in combination with androgen receptor (AR) agonists (5α-dihydrotestosterone [DHT] or Enobosarm), in modulating MD using a patient-derived explant (PDE) model of normal human mammary tissue. E2 alone increased MD in 3/6 cases, an effect influenced by menopausal status, whereas co-treatment with AR agonists reduced MD in all cases. Among known ER-regulated genes investigated, E2 commonly upregulated of TFF1, GREB1, CLIC6 and STMN1, and which was opposed AR agonism. A negative correlation between ER protein levels and MD change in PDEs (R2=0.4120 p=0.0023) was observed, a known feature of active ER signalling in breast cancer cells. Collectively, these findings suggest that activation of AR can oppose the promotional effects of ER on MD, and thus a potential mechanism for reducing breast cancer risk attributable to high MD.