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)

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

In this pilot clinical trial conducted in 10 postmenopausal women with advanced breast cancer, we evaluated the endocrine effects and toxicity of combined somatostatin analog and dopaminergic therapy in the attempt to suppress both growth hormone (GH) and prolactin (PRL) secretion. The patients' mean age was 63 years (range: 54-77) and the average number of previous treatments was 4.8 +/- 2 (SD). All patients were treated with the somatostatin analog SMS 201-995 (100-200 micrograms s.c. in a.m. and h.s.) and bromocriptine (2.5 mg orally twice a day). During treatment, GH levels following provocative testing (either L-DOPA or insulin-induced hypoglycemia) were suppressed in 7/9 patients. Basal somatomedin-S (Sm-C) levels declined in 6/9 women. Both GH and Sm-C levels decreased in 4 patients, while in the remaining 5 only one of the two parameters was lowered on treatment. PRL secretion (during provocative TRH testing) was almost totally abolished in 8/9 patients. The treatment did not affect circulating levels of FSH, LH, E1, E2, E1-S, T4, T3RU, or cortisol. Seven patients experienced no side effects. Nausea occurred in 3, but was severe enough in only one to require discontinuation of therapy. One patient experienced disease stabilization consisting of less than 50% regression of skin nodules and pleural effusion, a decline in CEA titer, and an improved performance status lasting 7 months. We conclude that combined SMS 201-995 and bromocriptine therapy is safe and frequently suppresses GH and PRL secretion. Its role in the treatment of metastatic breast cancer should be tested in patients with less advanced disease.
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PMID:Endocrine effects of combined somatostatin analog and bromocriptine therapy in women with advanced breast cancer. 257 6

Buserelin represents one of the main LHRH analogues. It appears to be effective in untreated metastatic breast cancer, whereas its activity in pretreated advanced patients remains to be established. To evaluate endocrine and clinical effects of buserelin in pretreated advanced mammary carcinoma, 14 postmenopausal women with metastatic breast cancer, which had been previously treated with hormones and/or chemotherapy, entered the study. Buserelin was subcutaneously injected at a daily dose of 1.5 mg for 7 days, then intranasally at a daily dose of 1.2 mg until progression. Before and after the 7 days of subcutaneous administration of the LHRH analogue, FSH, LH, estradiol, testosterone basal serum levels, and PRL response to TRH were examined. After the 7 days of buserelin subcutaneous injection, a significant decrease in FSH, LH and estradiol values was observed, whereas testosterone was not affected. PRL response to TRH did not change after buserelin subcutaneous treatment in 8 patients, it decreased in one and was completely abolished in the last 5 cases. All patients whose PRL response to TRH did not decrease had a progression within the first month of therapy, whereas only 1 of 6 patients whose PRL response to TRH was reduced or abolished following buserelin administration showed a progression. Among the other 5 cases, 2 minor responses and 3 stable diseases were achieved. These preliminary results suggest that buserelin has only a limited effectiveness in metastatic breast cancer patients who have been previously treated with hormones and/or chemotherapy, and that its activity in the control of tumor growth is associated with a reduction in PRL secretion.
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PMID:Endocrine and clinical effects of an LHRH analogue in pretreated advanced breast cancer. 284 Jul 64

In 120 Patients with metastatic breast cancer prolactin stimulation tests with 200 mcg TRH i.v. were done. The mechanism of the TRH-induced prolactin release was characterized in vitro. Basal prolactin levels were stimulated in all patients with an average increase of 400% (means basal level 441 mU/l, after stimulation 1753 mU/l). Hyperprolactinemic patients showed the highest absolute prolactin levels following stimulation. Patients with basal prolactin levels under 500 mU/l showed the highest relative increase of prolactin levels (delta = 550%). The prolactin stimulation tests with TRH had no diagnostic advantage compared to the basal prolactin levels in predicting the activity of the disease (basal values: sensitivity 12%, specificity 100%, stimulated values: sensitivity 10%, specificity 99%). During inhibition of plasmaprolactin with bromocriptine, an 330% increase of plasmaprolactin following TRH was observed in vivo. The same was shown in vitro: Pituitary cells cultured in vitro with 10(-6) M dopamine showed an increase of prolactin secretion after coincubation with 10(-7) M TRH. There was a linear increase of the prolactin concentration during the incubation period in dopamine-free cell cultures. The increase of prolactin concentration in vitro was constant during the whole incubation period (5 h), not influenced by the basal prolactin concentration and was seen as early as 30 min in incubation. The in vivo and in vitro results are in agreement with the hypothesis of a rapid, dopamine-independent effect of TRH on the secretion of stored prolactin in the pituitary.
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PMID:[Stimulation of prolactin secretion with thyroliberin (TRH). In vivo and in vitro studies of metastatic breast cancer]. 314 3

Megestrol acetate (MA) is of therapeutic value in breast cancer patients. This study was designed to evaluate the effects of different dosages of MA on endocrine events potentially influenced by the drug in relation to plasma level of MA and clinical effects in patients with advanced breast cancer. Eighteen postmenopausal patients were randomly distributed over six groups to receive daily 90, 180 or 270 mg of MA (niagestin) orally in a cross-over study consisting of 3 periods of 6 weeks. Complete remission was observed in 1 patient, partial remission in 9, no change in 4 and failure in 4 patients. During the 18 weeks of treatment plasma levels of MA gradually increased, irrespective of the dose administered. Significant rises of the basal and TRH-stimulated plasma PRL and basal insulin levels were observed, whereas LH and FSH, estradiol, SHBG and the pituitary-adrenal axis were suppressed. None of these metabolic effects showed a correlation with the clinical response. We concluded that treatment of metastatic breast cancer with 180 mg MA/day is effective and causes minimal adverse effects.
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PMID:Treatment of metastatic breast cancer patients with different dosages of megestrol acetate; dose relations, metabolic and endocrine effects. 636 95

Six postmenopausal patients with metastatic breast cancer, who responded to megestrol acetate after 6 weeks of treatment, were treated with the combination of megestrol acetate and tamoxifen during the next 6 weeks. The study was oriented towards the endocrine effects of this combination since it was known from our previous studies that megestrol acetate induces suppression of serum gonadotropins and of the pituitary-adrenal axis, a decrease of peripheral concentration of SHBG and of estradiol, and an increase of basal and TRH-stimulated plasma prolactin concentration. Tamoxifen, on the other hand, produces a decrease of prolactin and gonadotropins, whilst estradiol remains unaffected. Although the role of prolactin in the growth of human breast cancer has not been elucidated yet and there is no unequivocal evidence that a decrease in plasma prolactin could be of benefit for treatment of metastatic breast cancer, we tested whether addition of tamoxifen to the treatment regimen eliminated megestrol acetate-induced hyperprolactinaemia. The results show that addition of tamoxifen to megestrol acetate treatment annihilated the hyper-response of prolactin to TRH stimulation, while basal prolactin levels remained unaffected. The negative effect on plasma gonadotropin concentration appeared to be amplified, while estradiol and cortisol were not affected and SHBG increased. The results of these endocrine investigations merit a further study, directed to antitumor effects of this combination modality.
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PMID:Endocrine effects of the combination of megestrol acetate and tamoxifen in the treatment of metastatic breast cancer. 643 15