The complex nature of oestrogen signalling in breast cancer: enemy or ally?

The pleiotropic nature of oestradiol, the main oestrogen found in women, has been well described in the literature. Oestradiol is positioned to play a unique role since it can respond to environmental, genetic and non-genetic cues to affect genetic expression and cellular signalling. In breast cancer, oestradiol signalling has a dual effect, promoting or inhibiting cancer growth. The potential impact of oestradiol on tumorigenesis depends on the molecular and cellular characteristics of the breast cancer cell. In this review, we provide a broad survey discussing the cellular and molecular consequences of oestrogen signalling in breast cancer. First, we review the structure of the classical oestrogen receptors and resultant transcriptional (genomic) and non-transcriptional (non-genomic) signalling. We then discuss the nature of oestradiol signalling in breast cancer including the specific receptors that initiate these signalling cascades as well as potential outcomes, such as cancer growth, proliferation and angiogenesis. Finally, we examine cellular and molecular mechanisms underlying the dimorphic effect of oestrogen signalling in breast cancer.