title: Exploring breast cancer estrogen disposition: the basis for endocrine manipulation.
abstract: Although normal breast tissue and breast cancer estrogens are known to be elevated compared with plasma estrogen levels, the mechanism behind this phenomenon has been an issue of debate for 2 decades. If local estrogen aromatization were to be confirmed as the main estrogen source in breast cancer tissue, tissue-specific inhibition of estrogen production, avoiding systemic side effects, would become a potentially attractive option for breast cancer treatment and prevention. Based on recent results from our groups exploring tissue estrogens, together with estrogen-synthesizing and estrogen-regulated gene expression levels, we propose a new model to explain elevated breast tissue estrogen levels. Although local estrogen production may be important, the local contribution is overruled by rapid plasma-to-tissue equilibration, including active uptake of circulating estrogens or enhanced tissue binding. As for breast cancer tissue levels, elevated levels of estradiol may be explained to a large extent by estrogen receptor binding and local conversion of estrone into estradiol. This model indicates that effective suppression of benign and malignant tissue estrogens as a treatment for ER+ breast cancer requires systemic suppression and will not be markedly affected by local enzyme targeting.
authors.affiliation: Section of Oncology, Institute of Medicine, University of Bergen, and Department of Oncology, Haukeland University Hospital, Bergen, Norway. per.lonning@helse-bergen.no
authors.forename: Per E
authors.initials: PE
authors.lastname: Lønning
authors.forename: Ben P
authors.initials: BP
authors.lastname: Haynes
authors.forename: Anne H
authors.initials: AH
authors.lastname: Straume
authors.forename: Anita
authors.initials: A
authors.lastname: Dunbier
authors.forename: Hildegunn
authors.initials: H
authors.lastname: Helle
authors.forename: Stian
authors.initials: S
authors.lastname: Knappskog
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism*; D004967:Estrogens / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D015398:Signal Transduction
chemical_list: D004967:Estrogens