| Title | New endocrine therapies for oestrogen-dependent breast cancer | |
| Author | George Assimakopoulos
Breast Cancer Unit, Iaso Maternity Hospital, Athens, Greece |
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| Citation | Assimakopoulos, G.: New endocrine therapies for oestrogen-dependent breast cancer, Epitheorese Klin. Farmakol. Farmakokinet. 12(3): 91-100 (1998) | |
| Publication Date | Received for publication: 20 October 1998
Accepted for publication: 10 November 1998 |
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| Full Text Language | English | |
| Order – Buy | pharmakonpress[at]pharmakonpress[.]gr | |
| Keywords | Breast cancer, early, advanced, metastatic, endocrine therapy, anti-oestrogens, LHRH analogues, progestins, anti-progestins, aromatase inhibitors. | |
| Other Terms | review article | |
| Summary | Endocrine therapy for breast cancer has a long history, dating from the last years of the past century. Today, endocrine therapy is classified in four types: (a) surgical or medical castration by LHRH analogues (such as goserelin), (b) anti-oestrogens non-steroidal derivatives of triphenylethylene (mainly tamoxifen) and steroidal derivatives of oestradiol (ICI 182,780), (c) progestins and (d) aromatase inhibitors, steroidal (formestane, exemestane) and non-steroidal (such as fadrozole, letrozole, anastrozole). Anti-oestrogens act by competitively blocking the oestrogen receptors (ER); LHRH analogues act on the hypothalamic-pituitary axis to suppress ovarian function, decreasing luteinising hormone and oestradiol levels to post-menopausal values; aromatase inhibitors are characterised by their capacity to decrease the level of circulating oestrogen and by their selective anti-aromatase action which avoid using corticoids. Data from different trials demonstrated an objective response rate for goserelin, 3.6 mg, of 36.4% in premenopausal and perimenopausal patients with advanced breast cancer. 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, but has significantly less acute toxicity. Tamoxifen is widely used in the treatment of early breast cancer and as first-line endocrine therapy in metastatic disease. In advanced breast cancer, response rates of up to 60% in women with ER+ tumours have been reported. In early breast cancer, tamoxifen can produce significant benefits in terms of reduction in relative risk of relapse or death in all patients’ subgroups except premenopausal women with ER- tumours. The major benefit is seen in women over 50 years old with ER+ tumours. The results of randomised trials suggest that the optimum duration of tamoxifen therapy is at least 5 years. Phase II trials indicated that formestane has comparable activity to other endocrine treatments, white phase III trials have shown that its efficacy matches that of both tamoxifen and megestrol acetate when used as first and second-line endocrine therapy, with 54% and 51% of patients with advanced breast cancer achieving either objective response or stable disease. Overall survival was also similar. The systemic tolerability of formestane is comparable to that of tamoxifen and better than that of megestrol acetate. Letrozole, in two phase II studies, was shown to be an effective new treatment; in a phase ill trial, letrozole 2.5 mg once daily was shown to be more effective and better tolerated than megestrol acetate in the treatment of postmenopausal women with advanced breast cancer previously treated with anti-oestrogens. In two phase III studies, Anastrozole 1 mg and 10 mg once daily were compared with megestrol acetate. The lower dose was sufficient to suppress serum oestradiol to below the detection limit of the assay used. Both trials were performed in patients who had failed tamoxifen and who had ER- or ER unknown tumors; the results of both trials were identical and there were no significant differences in response rates between the two doses or between either dose of anastrozole and megestrol acetate. The once a day dosing and lack of weight gain with anastrozole make it more attractive than megestrol acetate for treatment of patients failing therapy with tamoxifen. None of the second and third generation aromatase inhibitors in trial have the toxicity associated with aminoglutethimide. The major side-effects are mild gastrointestinal disturbance and hot flushes in approximately 40% of patients. | |
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