Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Therapeutic access in the treatment of breast cancer with the antiestrogen tamoxifen has been established by world-wide clinical trials since the drug was introduced by Cole et al, in 1971. In recent years, however, a new series of antiestrogens (the derivatives of tamoxifen) such as trioxifene, toremifene and droloxifene have been studied with regard to clinical efficacy as a first-line treatment for postmenopausal patients with breast cancer and occasionally even for patients who previously responded to tamoxifen and then relapsed. Luteinizing hormone releasing hormone (LHRH) agonists are now available for premenopausal patients that will produce a medical castration, when given continuously, by down-regulation of the pituitary LHRH receptors. Four compounds, leuprolide, buserelin, tryptorelin and goserelin have been available for clinical use, but goserelin (Zoladex) is now widely used by long-acting depot preparations, which are given subcutaneously once every 4 weeks. Another series of drugs which inhibit estrogen synthesis in postmenopausal patients and are termed "aromatase inhibitors" have been developed. The pure aromatase inhibitors newly developed include two types of both a steroidal compound (4-hydroxyandrostenedione) and a non-steroidal one which is a tetrahydroimidazopyrimidine derivative (CGS 16949A). This review describes the pharmacological and clinical aspects of these new agents.
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PMID:[New drugs in endocrine treatment of breast cancer]. 132 43

333 pre- and peri-menopausal patients with breast cancer entered a programme of open studies on the effect of goserelin. Of the 333 patients, 265 patients were entered into assessable efficacy studies. Efficacy data were analysed from 228 eligible patients receiving 3.6 mg of goserelin administered as a subcutaneous injection of a depot formulation once every 28 days. Mean serum luteinising hormone (LH) and oestradiol concentrations were suppressed by day 22 after the first injection. Subjective response occurred in 68.3% of patients assessed. Objective response (UICC criteria) occurred in 36.4% of patients and the lifetable median duration of response was 44 weeks. Responses were observed in all histological grades of tumour, and regardless of oestrogen receptor status. Treatment was well tolerated with no withdrawals due to possible adverse reactions of which hot flushes (75.9%) and loss of libido (47.4%) were commonly encountered. Goserelin provides an effective well tolerated medical alternative to ovarian ablation in the management of advanced breast cancer.
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PMID:Goserelin depot in the treatment of premenopausal advanced breast cancer. 138 37

Twenty-two pre-menopausal evaluable patients with advanced breast cancer (median age 39 years; ER positive 19, unknown three; prior adjuvant chemotherapy 16) were treated with the LHRH agonist goserelin depot (Zoladex). Serum levels of 17 beta-estradiol and progesterone were suppressed by goserelin within 3-4 weeks of therapy, while serum leuteinizing hormone and follicle stimulating hormone titers remained in the low level of the normal range. Complete or partial response was documented in seven of 22 cases (32%) and occurred in all major sites of disease. Tumor response was documented in women regularly menstruating at the start of therapy. Median time to disease progression was 23 weeks; median duration of response was 64 weeks; overall survival was 141 weeks. Zoladex was well tolerated: only hot flushes in 82% and reversible cutaneous pigmentation in the site of injection in 45% of the patients were observed. In our experience the activity of Zoladex was comparable to that of oophorectomy, without the psychological trauma and the morbidity related to surgical castration.
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PMID:Treatment of pre-menopausal advanced breast cancer with goserelin--a long-acting luteinizing hormone releasing hormone agonist. 153 4

Goserelin is a synthetic analogue of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); or gonadorelin] which stimulates gonadotrophin and sex hormone release in the short term, and then causes suppression with continued administration. Goserelin is given as a subcutaneous biodegradable depot incorporating 3.6 mg of the drug, which is released continuously at an average rate of 120 micrograms/day over 4 weeks. Monthly goserelin depot therapy produces partial disease remission or stabilisation in about 75% of men with previously untreated prostatic cancer, a rate equivalent to that achieved with orchidectomy or diethylstilbestrol (stilboestrol). The response to goserelin is more rapid than to diethylstilbestrol, and goserelin is better tolerated. About 30 to 45% of premenopausal women with breast cancer responded to goserelin using objective assessment criteria, suggesting comparability to ovariectomy. In benign hormone-dependent conditions, preoperative goserelin aids surgical removal of uterine leiomyoma (fibroids) and reduces blood loss, and 6 months of therapy relieves the signs and symptoms of endometriosis. The elevation in testosterone at the beginning of goserelin therapy can result in disease 'flare' in men with prostate cancer, and sex steroid suppression with continued treatment results in hot flushes and loss of libido in most patients. Thus, goserelin is an effective alternative to surgery or estrogen therapy in prostatic cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. Other gynaecological conditions reliant on the pituitary-gonadal axis also appear amenable to hormone manipulation with goserelin.
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PMID:Goserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical use in sex hormone-related conditions. 170 53

For almost a century surgical castration represented the initial standard therapy for metastatic breast cancer in premenopausal women with hormone dependent tumors. Today the suppression of ovarian function can also be obtained by the administration of supraphysiologic doses of luteinizing hormone releasing hormone (LHRH) agonists. From April 1987 to February 1989, 23 premenopausal patients with advanced breast cancer (median age 39 years, range 28-52, ER positive 20, unknown 3; prior chemotherapy 17) were treated with the LHRH agonist goserelin depot (Zoladex) at the dose of 3.6 mg. every 4 weeks. Twenty-two patients were evaluable. Serum levels of 17 beta estradiol, progesterone, FSH and LH were suppressed by goserelin and fell to postmenopausal values within 8 weeks of therapy in 77% of cases. Complete response (CR) plus partial response (PR) was documented in 7 of 22 (32%) and occurred in all major sites of disease. Five patients achieved CR (soft tissue 3, viscera 2). Response rate was higher in patients not previously treated with chemotherapy (4/6). In the present series, all responses were seen in women greater than 35 years old, regularly menstruating at the start of treatment. Time to progression for the entire case series was 22 weeks and for responders 64 weeks. Oophorectomy was performed after disease progression in four patients without success. Goserelin was well tolerated. Local cutaneous dyschromia occurred in 45% and hot flushes in 82%. Treatment efficacy of goserelin is comparable to that of oophorectomy, without the psychological trauma and the morbidity related to surgical castration.
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PMID:Medical castration with zoladex: a conservative approach to premenopausal breast cancer. 182 40

From May 1987 to May 1989 sixty one pre- and perimenopausal women with advanced or recurrent breast cancer entered in an open non comparative study. They were treated, as a first-line therapy, with goserelin (Zoladex ICI-118630) a long acting gonadotropin-releasing hormone (LH-RH)-analogue in a depot formulation. Fifty three patients were evaluable for response; median age at entry was 41 years (range 28-56). Serum concentrations of 17 beta estradiol, LH and FSH were significantly suppressed within the first four weeks of therapy and remained suppressed for the whole duration of treatment. Subjective responses were observed, such as pain reduction and/or performance status improvement in 58% of patients. Overall objective response (CR + PR) occurred in 16 (30.2%) patients in all major sites of disease with a median time to response of 12 weeks (range 8 to 48 weeks) and a lifetable median duration of response of 36 weeks (range 16 to 76 weeks). The lifetable median time to progression was 17 weeks (range 5 to 76 weeks). Goserelin depot was well tolerated with no withdrawal due to possible adverse reactions. The observed subjective and objective response rates are comparable to those induced by surgical oophorectomy. Goserelin provides a well tolerated medical alternative to ovarian ablation, without the morbidity associated to surgery. In conclusion the present paper suggests that this innovative chemical estrogen deprivation, in premenopausal breast cancer patients, might be favorably investigated as an adjuvant therapy in future clinical trials.
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PMID:LH-RH analogue Zoladex in the treatment of pre- and perimenopausal women with metastatic breast cancer (results of the Italian Cooperative Study). 183 30

The specific binding of luteinizing hormone-releasing hormone (LH-RH) agonist in estradiol-dependent MCF-7 and estradiol-independent MDA-MB-231 human breast cancer cells has been studied using [3H]Ovurelin [(D-3H-Phe6),des-Gly10-LH-RH- ethylamide]. The results of Scatchard analyses suggest the presence of a single class of receptor sites, both in cell suspensions and membrane fractions. Evaluation of these peptide receptors appears to reflect additional characteristics of biological behaviour of these human breast cancer cells. The synthetic LH-RH agonist Ovurelin [(D-Phe6),des-Gly10-LH-RH-ethylamide] can directly interfere (25-30%) with the proliferation of MDA-MB-231 human breast cancer cells in culture. The inhibitory effect of Ovurelin in vitro was negligible in the MCF-7 cell line. In the in vivo experiments the treated immunosuppressed mice bearing either MCF-7 or MDA-MB-231 xenografts responded to the high-dose LH-RH analogue Zoladex depot and Decapeptyl depot therapy. Since the MDA-MB-231 tumour was found to be ER-negative it seems possible that the regression of this xenograft results from the direct antitumor action of the LH-RH agonist.
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PMID:Influence of luteinizing hormone-releasing hormone agonists on human mammary carcinoma cell lines and their xenografts. 200 34

The endocrinological and clinical effects of an LH-RH agonist, Zoladex, and an antiestrogen, Nolvadex, in patients with advanced breast cancer are outlined and their potential in the therapy of nonmalignant diseases of the breast and high-risk states is briefly discussed. Additional data are presented to indicate that new antiestrogens are now available for experimental studies that, unlike tamoxifen, do not possess partial estrogen-like activity and that show favorable antitumor properties against DMBA-induced mammary tumors and MCF-7 human breast cancer cells in culture. The lack of agonistic effects of this new class of pharmacological agents now allows a state of total estrogen deprivation to be approached, a previously unobtainable clinical goal.
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PMID:Estrogen deprivation in breast cancer. Clinical, experimental, and biological aspects. 214 73

The aromatase inhibitor, 4-hydroxyandrostenedione (4OHA) is an effective treatment for advanced post-menopausal breast cancer. The clinical and endocrine effects of 4OHA treatment were studied in five pre- and perimenopausal women with metastatic breast cancer. Serum oestradiol levels were not significantly reduced as a result of treatment with 500 mg of 4OHA by weekly i.m. injections and no patient had a tumour response. Four patients were subsequently treated with the luteinising hormone releasing hormone (LHRH) analogue, gosereline, and three had objective responses. The endocrine effects of combined treatment with goserelin (Zoladex), and 4OHA were studied in a further five premenopausal women. Serum oestradiol levels after treatment with goserelin alone were typical of post-menopausal women. Addition of 4OHA led to a further suppression of oestradiol to within the range observed in post-menopausal patients treated with further suppression of oestradiol to within the range observed in post-menopausal patients treated with 4OHA. Six patients whose tumours had regressed as a result of goserelin treatment and who subsequently relapsed were then given combined treatment. Four of the six experienced a second remission. We conclude that while 4OHA alone is unlikely to be a satisfactory treatment for premenopausal patients with advanced breast cancer, 4OHA in conjunction with goserelin leads to profound suppression of oestradiol. The combination of LHRH analogue and aromatase inhibitor may prove to be a superior treatment to LHRH analogue alone in these patients.
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PMID:The clinical and endocrine effects of 4-hydroxyandrostenedione alone and in combination with goserelin in premenopausal women with advanced breast cancer. 214 64

In premenopausal women with advanced breast cancer the luteinising hormone-releasing hormone agonist goserelin (Zoladex, ICI plc) will produce serum levels of oestradiol equivalent to those following surgical oophorectomy or the menopause. This paper reports our further experience of using this drug in 75 premenopausal patients with advanced breast cancer. In addition to response rates, duration of response is reported. An objective response was seen in 25 patients (33%), the median duration of which was in excess of 15 months. Seven patients (9%) showed a complete response to therapy; median duration greater than 37 months. There was no significant difference in time to disease progression (Lee-Desu statistic 18.26, 1 d.f., P = 0.43) and probability of survival (Lee-Desu statistic 3.41, 1 d.f., P = 0.07) between those patients assessed as having either static disease, or those showing a partial response at six months. Response to therapy correlates significantly with the oestrogen receptor status of the primary tumour (X2 = 20.59, 6 d.f., P less than 0.005). The modest side-effects, ease of administration and reversibility make this approach to therapy very attractive. This is to be remembered in that 53% of patients had disease progression whilst receiving goserelin. These patients thus avoided the unnecessary and irreversible morbidity associated with surgical oophorectomy. With the proven efficacy and minimal morbidity associated with goserelin we believe there is no current role for surgical oophorectomy in the management of premenopausal patients with advanced breast cancer.
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PMID:Goserelin (Zoladex) in premenopausal advanced breast cancer: duration of response and survival. 214 10


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