J. Steroid Biochem. Molec. Biol. Vol. 41, No. 3-8, pp. 541-543, 1992 0960-0760/92 $5.00 + 0.00 Printed in Great Britain. All fights reserved Copyright © 1992 Pergamon Press plc INFLUENCE OF TAMOXIFEN, AMINOGLUTETHIMIDE AND GOSERELIN ON HUMAN PLASMA IGF-I LEVELS IN BREAST CANCER PATIENTS E. A. LIEN, l* D. C. JOHANNESSEN, 2 A. AAKVAAG 3 and P. E. LONNING2 tMedical Department B, 2Department of Therapeutic Oncology and 3Department of Biochemical Endocrinology, Haukeland University Hospital, 5021 Bergen, Norway Summary--Plasma insulin-like growth factor-I (IGF-I) was measured in breast cancer patients before and during treatment with tamoxifen, goserelin or aminoglutethimide. 24 out of 27 postmenopausal women treated with tamoxifen 20 or 30 mg daily experienced a decrease in plasma IGF-I levels (mean levels before treatment 14.8 nM, during treatment 10.2nM, P < 0.001). In 8 out of 12 premenopausal breast cancer patients there was a reduction in plasma IGF-I during treatment with goserelin (mean levels before treatment 23.3 nM, during treatment 19.4 nM, P = 0.052). Contrary, 15 out of 17 postmenopausal women treated with the aromatase inhibitor aminoglutethimide had an increase in plasma IGF-I level (mean level before treatment 17.0 nM, during treatment 21.1 nM, P < 0.01). These preliminary results indicate that different forms of endocrine treatment of breast cancer may influence plasma IGF-I levels in different directions. INTRODUCTION Insulin-like growth factor-I (IGF-I, formerly named Somatomedin C) is a potent mitogen in several breast cancer cell lines in vitro [1, 2]. Several studies have documented IGF-I recep- tor sites in breast cancer specimens [3-5]. This suggests a biological role of this growth factor in breast cancer [6, 7]. The anti-estrogen tamoxifen is the endocrine treatment modality most frequently used for breast cancer today. Two recent studies re- ported suppression of plasma IGF-I by tamox- ifen in breast cancer patients [8, 9]. This effect could be of biological importance. Firstly, it may reduce the amount of IGF-I supplied from plasma to the tumor cells. Secondly, as IGF-I is synthesized by non-tumor cells [6], the possi- bility exists that mechanisms similar to those with an effect on plasma IGF-I may also influ- ence IGF-I synthesis in tumor vicinity. The mechanism(s) by which tamoxifen sup- press plasma IGF-I are not known. Oral estro- gen administration has been found to suppress plasma IGF-I in postmenopausal women [10]. Therefore, the possibility exists that tamoxifen suppresses plasma IGF-I levels through its es- Proceedings of the lOth International Symposium of the Journal of Steroid Biochemistry and Molecular Biology, Recent Advances in Steroid Biochemistry and Molecular Biology, Paris, France, 26-29 May 1991. *To whom correspondence should be addressed. trogen agonistic properties. Cells may respond to estrogen stimulation in vitro by secreting IGF-I-like activity into the medium [11]. In the present study we wanted to compare the effect of estrogen depletion with anti-estrogen treat- ment on IGF-I levels in breast cancer patients. The former effect was achieved with a luteiniz- ing hormone releasing hormone (LHRH) analogue in premenopausal women, and an aromatase inhibitor in postmenopausal women. Anti-estrogen treatment was achieved by use of tamoxifen. PATIENTS AND METHODS Three groups of patients were investigated: (1) 27 postmenopausal breast cancer patients (mean age 64.7 years, range 48 to 84 years) had tamoxifen either as 20mg o.d. (adjuvant therapy, n = 9) or 30 mg o.d. (metastatic dis- ease, n = 18); (2) 17 postmenopausal patients (mean age 70.3 years, range 56 to 78 years) had aminoglutethimide 250 mg q.i.d, with cortisone acetate 25 mg b.d. for metastatic breast cancer. All of these patients had previously been treated with tamoxifen, 10 of these patients also had previous therapy with high dose progestins (medroxyprogesterone acetate or megesterole- acetate) (Table 1); and (3) 10 premenopausal patients (mean age 40.0 years, range 33 to 51 years) had treatment with the LHRH analogue 541