Uptake of oestrogens into breast tissue and their subsequent metabolism can be studied by infusing radio-labelled steroids into volunteer patients. Such studies show that oestradiol is preferentially accumulated in breast tumours, oestradiol concentrations exceeding those of oestrone. This contrasts with plasma, in which oestrone concentrations in postmenopausal women are greater than those of the oestradiol. This observation suggests that tissue factors can modulate local oestrogen metabolism, and thus local steroid concentrations.
We have studied the local production of oestrogens from androgen, and also the interconversion of the major oestrogens, oestrone and oestradiol. Using isotopic techniques, it is possible to calculate the proportion of endogenous oestrogen produced from androgen, as opposed to uptake from the circulation. These studies suggest that a very variable proportion of tissue oestrogen derives from endogenous synthesis. After administration of aromatase inhibitors, aromatase activity is substantially inhibited, both in vivo and in vitro.
Relative oestrogen concentrations are determined in part by the activity of oestradiol dehydrogenase. In breast tissue, dehydrogenase activity is present and this is modified by various factors, including androgens. In addition, we have demonstrated that normal, benign and malignant breast tissues produce factors which can modulate both growth and dehydrogenase activity of cancer cells in vitro.
We conclude that breast tissue is a site of synthesis of oestrogens, and that a number of factors can affect their local concentration. Tumour cells produce growth factors which can influence steroid metabolism, and may thus be able to enhance favourably their own endocrine environment.