LHRH-agonist treatment in clinical and experimental human breast cancer

Thirty-one premenopausal patients with metastatic breast cancer were treated for 3-33 months with the potent LHRH-agonist Buserelin (Hoe 766) as a first-line therapy. Twelve women (group IA) were treated with a daily dose of 3 X 400 micrograms Buserelin intranasally and 10 women (group IB) with a daily dose of 2 X 1 mg subcutaneously after parenteral treatment with 3 mg per day in the first week. Nine patients (group II) were treated chronically with 3 X 400 micrograms Buserelin intranasally in combination with 2 X 20 mg tamoxifen (n = 5, group IIA) or 4 X 45 mg megestrol acetate (n = 4, group IIB). A great variation in hormonal response with recurrent peaks of E2 in about half of the patients was observed in groups IA and IIA, while in group IB and IIB a "chemical castration" was reached in all patients with the most pronounced suppression of E2 secretion in group IB. An objective tumour response was found in 13 (42%) and stable disease in 7 (23%) out of 31 patients. Nine out of 22 patients (41%) treated with Buserelin alone showed an objective response. In 8 of 17 patients (48%) with an estradiol receptor-positive tumour and in one of 2 patients with an ER-negative tumour we observed an objective remission. In an experimental study we found that Buserelin has a weak direct anti-estrogenic effect on the growth of human mammary tumour cells (MCF-7) in vitro. In conclusion medical treatment with high doses of Buserelin appears as effective as surgical castration in premenopausal metastatic breast cancer with an absence of serious side effects.