Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Steroid hormone action in the normal human breast and in breast cancer (#73)

Heidi Hilton 1
  1. Westmead Millennium Institute, Westmead, NSW, Australia

The epithelium of the human breast is made up of a branching ductal-lobular system, which is lined by a single layer of luminal cells surrounded by a contractile basal cell layer. The co-ordinated development of stem/progenitor cells into these luminal and basal cells is fundamentally important for breast morphogenesis. The ovarian steroid hormones, estrogen (E) and progesterone (P),which signal through their receptors, ER and PR, are critical in driving this normal breast development. However, the cumulative exposure to the cycling levels of E and P throughout a woman’s reproductive life significantly influences the overall risk of developing breast cancer, and women exposed to progestin-containing hormone replacement therapy (HRT) have an increased breast cancer risk compared to women taking estrogen (E) alone, or no HRT at all. How exposure to these hormones increases breast cancer risk, however, is unknown. We have shown that P treatment increases proliferation and expands the human breast bipotent progenitor cell compartment, and that P stimulates progenitor cells in human breast cancer cell lines and expands the breast cancer stem cell-like population. In addition, we have shown that PR is expressed in different epithelial populations compared with ER in the normal human breast, and that PR becomes highly correlated with ER in breast cancer, supporting the view that the mechanisms of E and P action are distinct in the normal breast, but that they converge in breast cancer. These findings challenge the established paradigm that ER and PR are co-expressed in normal breast, and have significant implications regarding not only our understanding of normal biology in the human breast, but also regarding diagnosis, prognosis and/or treatment options in breast cancer patients.