Abstract
Current standard adjuvant therapies for early breast cancer include tamoxifen and chemotherapy, depending on the disease prognosis and menopausal status. Luteinizing hormone-releasing hormone (LHRH) analogues offer a different approach to the management of early breast cancer in pre- and perimenopausal women. The most widely studied LHRH analogue is goserelin. It acts on the hypothalamic-pituitary axis to suppress ovarian function, decreasing luteinizing hormone and oestradiol levels to post-menopausal values. Pooled data from 228 premenopausal and perimenopausal patients with advanced breast cancer enrolled in 29 studies worldwide demonstrated an objective response rate for goserelin, 3.6 mg, of 36.4%, with a median duration of response of 44 weeks. These results fall well within the ranges of reported response rates for ovarian ablation and for tamoxifen in similar patient populations. By virtue of its mode of action, goserelin does not stimulate the ovaries and is unlikely to have detrimental effects on the endometrium. In addition, given that goserelin has no oestrogen agonist-like effects, unlike tamoxifen, there is no potential for tumour stimulation in those patients becoming resistant to treatment. Goserelin is generally well tolerated, and the main side-effects are related to ovarian suppression, which is potentially reversible. Preliminary results in premenopausal women with early breast cancer indicate that endocrine treatment with goserelin plus tamoxifen may be as effective as standard combination chemotherapy (cyclophosphamide-methotrexate-5-fluorouracil), but has significantly 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.
Highlights
A number of large, randomized trials are in progress to assess the potential role of goserelin as adjuvant therapy for early breast cancer
This paper provides a brief review of the mechanism of action of goserelin and its potential benefits in early breast cancer
The role of Luteinizing hormone-releasing hormone (LHRH) analogues such as goserelin in the adjuvant and this may be associated with detrimental effects on the treatment of early breast cancer in premenopausal women remains endometrium (Barakat, 1996) and sometimes on the tumour itself to be defined
Summary
Goserelin acts on the hypothalamic-pituitary axis, achieving ovarian suppression by receptor down-regulation. LHRH binds to a proportion of the LHRH receptors on the surface of pituitary cells. The occupied receptors form clusters and pass through the cell surface into the cell itself. As not all receptors are occupied by the pulse of LHRH, and because there is constant receptor resynthesis, pituitary cells can respond to a subsequent LHRH stimulus (Clayton and Catt, 1981). Administration of goserelin initially leads to occupation of a high proportion of LHRH receptors (Figure 1). There is a short-lived rise in serum LH concentration, resulting in increased oestradiol production by the ovaries (Thomas et al, 1986). The occupied LHRH receptors again form clusters and gradually disappear into the cell, but chronic administration of
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