Endocrine effects of the combination of megestrol acetate and tamoxifen in the treatment of metastatic breast cancer.

Six postmenopausal patients with metastatic breast cancer, who responded to megestrol acetate after 6 weeks of treatment, were treated with the combination of megestrol acetate and tamoxifen during the next 6 weeks. The study was oriented towards the endocrine effects of this combination since it was known from our previous studies that megestrol acetate induces suppression of serum gonadotropins and of the pituitary-adrenal axis, a decrease of peripheral concentration of SHBG and of estradiol, and an increase of basal and TRH-stimulated plasma prolactin concentration. Tamoxifen, on the other hand, produces a decrease of prolactin and gonadotropins, whilst estradiol remains unaffected. Although the role of prolactin in the growth of human breast cancer has not been elucidated yet and there is no unequivocal evidence that a decrease in plasma prolactin could be of benefit for treatment of metastatic breast cancer, we tested whether addition of tamoxifen to the treatment regimen eliminated megestrol acetate-induced hyperprolactinaemia. The results show that addition of tamoxifen to megestrol acetate treatment annihilated the hyper-response of prolactin to TRH stimulation, while basal prolactin levels remained unaffected. The negative effect on plasma gonadotropin concentration appeared to be amplified, while estradiol and cortisol were not affected and SHBG increased. The results of these endocrine investigations merit a further study, directed to antitumor effects of this combination modality.