EFFECT OF ACUTE AND CHRONIC ADMINISTRATION OF TAMOXIFEN ON GH RESPONSE TO GHRH AND ON IGF-I SERUM LEVELS IN WOMEN WITH BREAST-CANCER

Tamoxifen, an estrogen antagonist, is usually employed in the treatmen t of breast cancer. Its mechanism of action is not well known because an antiproliferative effect of the drug has been shown also in estroge n receptor negative tumors, most likely mediated by the inhibition of local growth factors and particularly IGF-I. However, the action of ta moxifen on the GH-IGF-I axis is still open to investigation, We have i nvestigated the influence of acute and chronic treatment with tamoxife n on GH response to GHRH and IGF-I serum levels in six postmenopausal women with metastatic breast cancer. A GHRH test (50 mu g i.v. at time 0, GH determinations at 0, 15, 30, 60, 90 and 120 min) was performed (a) basally, (b) 3 h after 40 mg oral administration of tamoxifen and (c) after 8 weeks of 20 mg twice a day oral tamoxifen treatment. IGF-I was measured basally and after chronic tamoxifen therapy. No signific ant modifications in GH response to GHRH were observed after acute or chronic treatment with tamoxifen vs the basal test. On the contrary, c hronic tamoxifen treatment induced a significant decrease in serum IGF -I levels. Basal pretreatment levels of 123 +/- 18 mu g/l were suppres sed to 65 +/- 11 mu g/l (mean suppression 47%, P < 0.001). These preli minary data confirm the inhibitory effect of tamoxifen on IGF-I produc tion but seem to exclude the possibility that this effect may be due t o an inhibition of GH secretion.