LUTEINIZING-HORMONE-RELEASING HORMONE ANALOGS THE RATIONALE FOR ADJUVANT USE IN PREMENOPAUSAL WOMEN WITH EARLY BREAST-CANCER

Current standard adjuvant therapies for early breast cancer include ta moxifen and chemotherapy, depending on the disease prognosis and menop ausal status. Luteinizing hormone-releasing hormone (LHRH) analogues o ffer a different approach to the management of early breast cancer in pre- and perimenopausal women. The most widely studied LHRH analogue i s goserelin. It acts on the hypothalamic-pituitary axis to suppress ov arian function, decreasing luteinizing hormone and oestradiol levels t o post-menopausal values. Pooled data from 228 premenopausal and perim enopausal patients with advanced breast cancer enrolled in 29 studies worldwide demonstrated an objective response rate for goserelin, 3.6 m g, of 36.4%, with a median duration of response of 44 weeks. These res ults fall well within the ranges of reported response rates for ovaria n ablation and for tamoxifen in similar patient populations, By virtue of its mode of action, goserelin does not stimulate the ovaries and i s unlikely to have detrimental effects on the endometrium. In addition , given that goserelin has no oestrogen agonist-like effects, unlike t amoxifen, there is no potential for tumour stimulation in those patien ts becoming resistant to treatment. Goserelin is generally well tolera ted, and the main side-effects are related to ovarian suppression, whi ch is potentially reversible. Preliminary results in premenopausal wom en with early breast cancer indicate that endocrine treatment with gos erelin plus tamoxifen may be as effective as standard combination chem otherapy (cyclophosphamide-methotrexate-5-fluorouracil) but has signif icantly less acute toxicity. A number of large, randomized trials are now in progress to assess the potential role of goserelin as adjuvant therapy for early breast cancer.