The relevance of local oestrogen metabolism within the breast

Abstract

SynopsisOvarian oestrogens appear to have a central role in the development of the breast. However, peripheral tissues including the breast and its tumours have the potential to synthesise and metabolise oestrogens. When ovarian secretion of hormones is low, for example, after the menopause, such extra-gonadal steroidogenesis may assume biological significance.While no individual steroid conversion in the breast has been shown to correlate with levels of endogenous oestrogens, certain positive associations have been observed between enzyme activities and the presence, stage and hormone dependence of breast cancer.Thus biosynthesis of oestrogen (aromatisation) in breast fat is significantly higher in patients with breast cancer as compared to that from women with benign breast disease. Within the breasts of women with cancer, oestrogen biosynthesis is enhanced in quadrants bearing tumour. In contrast, levels of 17β-hydroxysteroid dehydrogenase are not associated with the presence of malignancy, but in women with breast cancer, activity is significantly higher in breast fat of patients with large tumours and those with nodal metastasis. There is also evidence that oestrogen sulphurylation in breast cancer is associated with hormone dependence and among postmenopausal patients with oestrogen-receptor-positive tumours, response to the aromatase inhibitor, aminoglutethimide, is restricted to cancers possessing aromatase activity.