Journal of Steroid Biochemistry & Molecular Biology 104 (2007) 27–34 Total body aromatization in postmenopausal breast cancer patients is strongly correlated to plasma leptin levels  J¨ urgen Geisler a,c , Ben Haynes b , Dagfinn Ekse a , Mitch Dowsett b , Per Eystein Lønning a,c,∗ a Department of Oncology, Haukeland University Hospital, Bergen, Norway b Academic Department of Biochemistry, Royal Marsden Hospital, London, UK c Section of Oncology, Institute of Medicine, University of Bergen, Norway Received 3 March 2006; accepted 17 September 2006 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 95.51ng/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 ≤ 0.001, estrone sulfate r s 0.353, P ≤ 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. © 2007 Published by Elsevier Ltd. Keywords: Breast cancer; Leptin; Estrogens; Aromatase; Androgens 1. Introduction Obesity is a well-established risk factor for breast can- cer development in postmenopausal women [1–5]. Although adipose tissue is one of the major sites for the conver- sion of androgen precursors into estrogens (“aromatization”) in postmenopausal women, and elevated plasma estrogen  Presented in part at the 28th Annual San Antonio Breast Cancer Sym- posium, December 8–11, 2005, San Antonio, TX, USA. ∗ Corresponding author. Tel.: +47 55 97 2010; fax: +47 55 97 3599. E-mail address: per.lonning@helse-bergen.no (P.E. Lønning). levels have been associated with an increased breast can- cer risk [6–8], the direct link between obesity and breast cancer has not yet been identified. Recently, a variety of adipocyte-derived polypeptides (“adipocytokines”) [9] like leptin, adiponectin, tumor necrosis factor-alpha (TNF- ), interleukin-6 (IL-6), heparin-binding epidermal growth factor-like growth factor (HB-EGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) have been suggested to exert paracrine and endocrine effects on normal and neoplastic breast tissue [10]. The current publication focuses on leptin, a 16 kda pro- tein encoded by the LEP (previously called ob for obesity) 0960-0760/$ – see front matter © 2007 Published by Elsevier Ltd. doi:10.1016/j.jsbmb.2006.09.040