Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tamoxifen is a synthetic nonsteroidal drug with antiestrogenic properties. This report describes the response of patients with metastatic breast cancer to tamoxifen and correlates clinical responses with tumor tissue content of cytoplasmic estrogen binding proteins (EBPs) and other biochemical parameters. Ages of patients ranged from 27 to 82 years. 7 patients were premenopausal, 63 postmenopausal, and 2 had recent endocrine ablaetion. Prior hormone therapy, radiotherapy, or chemotherapy ahd been given to all patients. Tamoxifen was given at a dose of 20 mg orally for a minimum of 4 weeks and continued if an objective remission was shown. Before therapy a biopsy specimen was taken for determination of EBP and for specific enzyme activities. Another biopsy specimen was taken for at least 8 weeks after therapy. A total of 72 patients were treated for at least 4 weeks. The overall response rate was 38%. Most frequent responses were in the over-70 age group. The median duration of response has been 9.5 months. Bony involvement responded to therapy in 21 of 28 patients. No responses were shown in 6 patients with liver metastases. Only 1 of 18 patients who had previous chemotherapy responded. Of 31 who had no prior chemotherapy, 73% achieved a remission. There was a 44% correlation between patients with a positive EBP assay and response to therapy, but none in EBP-negative patients. In this study 20 of 28 patients had normal arylsulfatase B/DNA ratios in their tumor tissue and 11 of the 20 responded to tamoxifen therapy. Patients who responded most favorably to therapy had normal G-6-PD activities. It is concluded that tamoxifen therapy may cancel the need for ablative surgery in postmenopausal patients with positive EBPs and who have had a prior response to additive hormonal treatment.
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PMID:Therapeutic use of tamoxifen in advanced breast cancer: correlation with biochemical parameters. 19 Nov 85

The antiestrogen Tamoxifen (T), given orally to 113 patients with stage IV breast cancer, induced objective remission in 50%. Duration of remission in the first 39 patients, with minimum 27 months follow up, is 18 + months; these results are equal to those of surgical hypophysectomy. T prolonged survival in responders. Older age, previous response to endocrine therapy and positive estrogen receptors predicted response to T. T was effective in hypophysectomized patients in whom serum growth hormone and prolactin were undetectable, but serum ostrogens were present in low amount, suggesting a direct stimulatory effect of estrogens at the tumor level. Hypophysectomy induced further palliation after treatment with T, indicating that pituitary hormones may also play a role in the growth of some human breast cancers. Side effects from T were minimal. T is the initial treatment of choice for postmenopausal women with hormone responsive stage IV breast cancer.
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PMID:Antihormone treatment of stage IV breast cancer. 42 Nov 71

Transsphenoidal hypophysectomy was performed in 212 consecutive patients with metastatic breast cancer: 11 died within 30 days, two of surgical complications and nine of advanced metastatic disease. Two patients were unevaluable because of inadequate follow-up in one and simultaneous radiation treatment in the other. Of 199 evaluable patients 42% had an objective remission. Duration of remission averaged 18+ months with 10 out of 84 patients still in remission. Presence of estrogen receptors in the tumor significantly predicted response to hypophysectomy. Of 156 patients in whom completeness of hypophysectomy was assessed, 128 were thought to have a complete removal as shown by the fact that their growth hormone and prolactin were undetectable after stimulation with arginine or chlorpromazine, respectively. Of 26 patients in whom TRH test was performed, TSH and prolactin were undetectable in 20. Of 23 patients where autopsy was performed only six had microscopic pituitary tissue remaining. Hypophysectomy induced remission in eight of 15 patients who had previously responded and then relapsed to the antiestrogen Tamoxifen and in four of 17 who had failed. Conversely, antiestrogen therapy induced remission in six of 26 patients who had previously responded to hypophysectomy and in whom serum estrogens were present in small amount. These data indicate that both gonadal and pituitary hormones play a role in the growth of some human breast cancers.
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PMID:Transsphenoidal hypophysectomy in breast cancer: evidence for an individual role of pituitary and gonadal hormones in supporting tumor growth. 50 1

Tamoxifen (ICI 46474), an antiestrogen, was given to 89 selected patients with stage IV breast cancer at a dose of 20 mg orally every 12 hours. Forty-seven percent of the patients had objective tumor regression averaging 11+ months with 25 of 42 women still in remission. In the first 39 patients where the minimum follow-up period is 16 months the average duration of remission is more than 15 months with 8 of 19 patients still in remission. These results are approaching those of surgical hypophysectomy, where, in our experience the average remission lasts about 18 months. Thus, Tamoxifen is a highly effective antitumor agent and is probably the initial treatment of choice for women with hormone responsive breast cancer. Antiestrogen induced objective remissions in 5 of 19 patients who had previously responded to surgical hypophysectomy, and 5 additional patients showed no progression of disease lasting 15+ months. Estradiol and estrone were detectable in the serum of these patients whereas, prolactin and growth hormone were not detectable. Thus, antiestrogen can induce remissions in some patients in the absence of the pituitary gland, and this constitutes additional palliation and provides evidence that estrogens can directly stimulate tumor growth. Four of 7 patients who obtained remissions from Tamoxifen obtained further improvement from hypophysectomy, and 1 of 8 patients who failed to benefit from antiestrogen improved after hypophysectomy. These results suggest that prolactin and growth hormone may also play a role in stimulating tumor growth in some patients.
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PMID:Treatment of breast cancer with antiestrogen: approach to medical hypophysectomy? 61 66

Tamoxifen, a phenylstilbene derivative, is currently being used to treat metastatic breast cancer. We describe an analytical method for monitoring the parent drug and its 4-hydroxylated derivative in whole blood and plasma. After extraction from biological media, the analytes are converted to highly fluorescent products by ultraviolet irradiation, and then separated by liquid-chromatography on a muBondapak CN column, with spectrofluorometric detection of components. Detection limits for tamoxifen and its 4-hydroxy derivative are 1 and 2 microgram/liter of biological fluid, respectively. Conditions have been optimized so that the reaction proceeds fast enough for convenient sample handling without jeopardizing fluorescence yield due to the photocatalyzed degradation of the fluorescent product. Evidence suggests that the fluorophore being monitored is a phenanthrene derivative.
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PMID:Clinical analysis of tamoxifen, an anti-neoplastic agent, in plasma. 68 11

The detection of specific hormone receptors in normal and tumor tissue has brought new insight into the mechanisms of action of hormones and anti-hormones. The Swiss Cooperative Cancer Study Group (SAKK) has evaluated the antitumor effect of the new antiestrogenic substance tamoxifen in metastatic breast cancer. 158 postmenopausal patients treated with 20 mg/d tamoxifen by mouth are evaluable at present time. Complete and good partial remissions were achieved in 39 patients (25%) largely with soft tissue but also lung and bone metastases. Tamoxifen was well tolerated and caused few serious complications such as thrombosis/pulmonary embolism and hypercalcemia. These results confirm already published experience with tamoxifen, which may replace the estrogens as the primary endocrine treatment in postmenopausal mammary carcinoma metastasizing to soft tissues, lung and bone.
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PMID:[Antiestrogens: a new endocrine treatment possibility in metastasizing breast neoplasms. Experiences of the Swiss Cooperative Cancer Study Group with tamoxifen]. 69 81

The antiestrogen tamoxifen is the most widely used hormonal therapy for breast cancer. The drug exerts its antiproliferative effects primarily through estrogen receptor (ER)-mediated mechanisms, although other cellular actions may augment tumor inhibition. Clinically, tamoxifen has been less well studied in premenopausal than in postmenopausal patients. The drug has complex endocrine effects that are dependent on the treatment duration and dose, menopausal status, and target organ. In postmenopausal women receiving tamoxifen, serum estrogen levels remain low, and the normally elevated gonadotropin levels decrease. In contrast, serum estrogen levels are strikingly elevated in many premenopausal women, and gonadotropin concentrations are either unchanged or slightly increased. Large systematic trials in metastatic breast cancer have established tamoxifen as the recommended hormonal therapy for postmenopausal women with ER-positive tumors. Tamoxifen is also an active agent for premenopausal metastatic disease, and response rates are comparable to those reported for oophorectomy. Clinical experience with tamoxifen in this younger age group, however, is more limited. Few premenopausal women (less than 400) have been included in phase II and phase III trials. Two randomized trials (total of 160 patients) comparing oophorectomy with tamoxifen do not definitively establish therapeutic equivalence, and a survival advantage for either treatment cannot be excluded. Many questions remain concerning the appropriate role for tamoxifen in premenopausal patients. Still, tamoxifen has an attractive toxicity profile, and it offers a favorable therapeutic alternative for premenopausal women with ER-positive metastatic breast cancer who wish to avoid surgical or radiation castration.
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PMID:Tamoxifen in premenopausal patients with metastatic breast cancer: a review. 204 68

Sequential administration of endocrine therapies can result in objective remission in a significant fraction of patients with metastatic breast cancer. Combined hormonal therapies and combined hormonochemotherapies have not resulted in better results than the sequential administration of these same therapies. Tamoxifen (an antiestrogen) given as an initial therapy results in local control of the disease in a significant fraction of patients with locally advanced breast cancer who are not candidates for cytotoxic therapy. Tamoxifen as an adjuvant therapy for operable breast cancer prolongs disease-free survival and reduces mortality in patients greater than 50 yr of age with higher estrogen receptor concentrations. The role of tamoxifen as adjuvant therapy for patients less than 50 yr of age remains unclear. Also, adjuvant tamoxifen in combination with cytotoxic drugs has not produced superior results, and the duration of adjuvant tamoxifen therapy remains to be determined. Experimental data suggest prolonged administration of tamoxifen may be needed to control micrometastases.
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PMID:Current status of endocrine treatment of carcinoma of the breast. 218 45

Testosterone is a known estrogen precursor especially in postmenopausal women. Tamoxifen, an anti-estrogen, is used in the treatment of women with breast cancer in whom metastatic disease has been demonstrated. The action of Tamoxifen is thought to be to occupy the intracellular estrogen receptor sites in target tissues and thus block the action of the biologically active estrogen, estradiol. Effects of Tamoxifen on the production and metabolism of hormones have been postulated. We studied the kinetics of testosterone metabolism by the constant infusion of 3H-testosterone in six postmenopausal women with breast cancer prior to and during Tamoxifen therapy. The Tamoxifen did not produce any significant change in the metabolic clearance rate, the plasma concentration or the calculated blood production rate of testosterone. The only significant alteration in the conversion ratio of testosterone to metabolites was the reduction (p less than 0.02) in conversion to 5 alpha-dihydrotestosterone. A significant reduction in the plasma concentrations (p less than 0.05) of dehydroepiandrosterone and of luteinizing hormone (p less than 0.02) was found. Other steroid and peptide hormones did not show any significant changes. We conclude that Tamoxifen therapy has very little effect on the kinetics of testosterone metabolism in postmenopausal women with metastatic breast cancer.
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PMID:Effects of tamoxifen on testosterone metabolism in postmenopausal women with breast cancer. 293 65

The modified therapeutic approach to metastatic breast cancer has been influenced by the realization that it cannot be cured even with the most aggressive chemotherapy. Consequently, quality of life and duration of remission have become more important parameters than judging therapeutic success only by rate of remission. The discovery of hormone receptors and of potent drugs with few side effects, which replaced ablative procedures, has led to an increased significance of endocrine therapy. Improved understanding of the endocrine mechanisms regulating malignant growth and their relationship to growth factors and tumor associated proteolysis have concurrently stimulated clinical research. Endocrine manipulation of malignant growth is based on competitive (antihormones), inhibitive (aromatase inhibitors, LHRH agonists), additive (gestagens) and ablative (ovarectomy) mechanisms. The knowledge of the optimal sequence and modality is mandatory for an individualized treatment, leading to significant advantages for the majority of patients. Premature induction of cytotoxic polychemotherapy may even cause disadvantages for subgroups of patients and should only be used as primary therapy in those situations, where urgent remission is mandatory. Only after all endocrine therapies have been tried and evaluated, one should turn to chemotherapy, whereby a trend towards "soft" chemotherapy, often as monotherapy, is favoured. The development of new substances, such as long acting LHRH analogues, "pure" antiestrogens with high receptor affinity, highly potent selective aromatase inhibitors and also the discovery of anti-progestins lead to further improvement of endocrine therapy in relation to efficacy as well as reduction of side effects. Adjuvant endocrine therapy with Tamoxifen correlates positively with the course of the disease and the survival rate in postmenopausal women. Unfortunately no effective adjuvant hormone therapy in premenopausal women exists to date.
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PMID:[Endocrine therapy of breast cancer. Status and perspectives]. 306 56


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