The use of gonadotrophin-releasing hormone (GnRH) agonists in early and advanced breast cancer in pre- and perimenopausal women

Abstract

Gonadotrophin-releasing hormone (GnRH) agonists, in particular goserelin (‘Zoladex’), are increasingly being used for the treatment of breast cancer in women with functioning ovaries. They act by downregulating pituitary GnRH receptors, thereby suppressing the release of luteinising hormone (LH) and follicle stimulating hormone (FSH), which, in turn, reduce the main source of oestradiol production in the ovaries. GnRH agonists have been shown to be as effective therapeutically as surgical ovarian ablation in pre- and perimenopausal women with advanced breast cancer. The combination of a GnRH agonist such as goserelin with the peripheral oestrogen antagonist, tamoxifen, may be used to produce ‘combined oestrogen blockade’. In advanced breast cancer, this regimen prolongs progression-free survival and increases both the response rate and duration relative to the use of a GnRH agonist alone. In patients with early breast cancer, the addition of goserelin to ‘standard treatment’ (i.e. surgery±tamoxifen, chemotherapy or radiotherapy) results in a significant benefit in recurrence-free survival and overall survival. This benefit was most apparent in patients with oestrogen receptor (ER) +ve tumours. Goserelin, when used either alone or in combination with tamoxifen as an adjuvant systemic therapy in women with ER +ve tumours, has been shown in clinical trials to produce recurrence-free survival rates equivalent to cytotoxic chemotherapy such as cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Evidence suggests that at least part of the effect of adjuvant cytotoxic chemotherapy in premenopausal women is produced by ovarian ablation. Endocrine therapy with goserelin or goserelin plus tamoxifen should now be considered a treatment option in the management of premenopausal women with ER +ve early breast cancer.