Endocrinology of the Breast
Local steroid metabolism in breast tissue
Breast cancer is the most common malignancy in women. The majority is estrogen-receptor-positive, and therefore the incidence of breast cancer also depends on the endo- and exogenous hormonal exposure. However, the majority of women develop breast cancer after menopause, when plasma levels of estradiol (E2) have decreased by 90% due to ovarian exhaustion. The most biologically active estrogen in breast tissue is 17β-E2. Breast tissue and mammary cancer cells possess the enzymatic systems necessary for the intratumoral biosynthesis of estrogens from precursor molecules circulating in plasma. Three main enzymes are important in this process: aromatase, which converts androgens to estrogens, estrone-sulfate (E1S)-sulfatase (STS) which hydrolyzes E1S to estrone (E1), and 17β-hydroxysteroid dehydrogenase type 1 (17βHSD-1) which reduces E1 to E2. Local estrogen formation has been shown to be higher in normal premenopausal in comparison to postmenopausal breast tissue [Stute P et al. 2007]. However, the local estrogen formation in normal breast tissue is increased by postmenopausal hormone therapy [Stute P et al. 2008 and 2006]. The hypothesis is that there is a dynamic local endocrine milieu which might be influenced by endo- and exogenous hormones thus affecting breast cancer risk. The overall aim of the research plan is to study the impact of postmenopausal hormone therapy on normal and malignant breast tissue including the regulation of mammarian stem cells and local estrogen formation.