title: Total body aromatization in postmenopausal breast cancer patients is strongly correlated to plasma leptin levels.
abstract: The adipocytokine leptin has recently been shown to enhance the expression of aromatase via promoter II and I.3 using an AP-1 motif. Thus, we evaluated the correlation between plasma leptin concentrations and total body aromatization (TBA) as well as plasma levels of estrone (E(1)), estradiol (E(2)) and estrone sulfate (E(1)S) in postmenopausal breast cancer patients. Twenty-two postmenopausal women with metastatic breast cancer, participating in tracer studies for the measurement of total body aromatization (TBA) in vivo, were available. In addition, blood samples for plasma estrogens and leptin measurements were available from another 22 breast cancer patients and 114 healthy postmenopausal women participating in the mammography-screening program. Values for TBA varied from 1.46 to 4.72% while plasma leptin levels ranged from 1.83 to 95.51 ng/ml in the same group of patients. All plasma estrogen levels were in the normal range expected for postmenopausal women. We found a significant correlation between pretreatment leptin levels and TBA (r(s) 0.452, P=0.01). In contrast, basal levels of TBA did not correlate to body mass index (BMI) in the same group of patients. Plasma leptin levels correlated to plasma levels of estradiol (r(s) 0.659, P=0.007), and estrone sulfate (r(s) 0.562, P=0.01) in the group of breast cancer patients (n=44) as well as in the group of healthy postmenopausal women (estradiol, r(s) 0.363, P< or =0.001, estrone sulfate r(s) 0.353, P< or =0.001). In conclusion, we found plasma leptin levels to correlate to TBA in breast cancer patients and to plasma levels of estradiol and estrone sulfate in breast cancer patients as well as in healthy postmenopausal females. These findings suggest that leptin may influence on aromatase activity in vivo, providing a possible link between body weight and plasma estrogen levels as well as breast cancer risk.
authors.affiliation: Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisler
authors.forename: Ben
authors.initials: B
authors.lastname: Haynes
authors.forename: Dagfinn
authors.initials: D
authors.lastname: Ekse
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
mesh_terms: D000368:Aged; D000735:Androstenedione / Q000008:administration & dosage / Q000378:metabolism; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000494:pharmacology; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000201:enzymology*; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause
chemical_list: D047072:Aromatase Inhibitors; D020738:Leptin; D004970:Estrone; D000735:Androstenedione; D004958:Estradiol; D001141:Aromatase; C017296:estrone sulfate