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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Continuous administration of gonadotrophin-releasing hormone (GnRH-)analogues leads to a receptor-down regulation of pituitary GnRH-receptors and subsequently inhibits ovarian hormone production. Since October, 1984, 118 evaluable pre- and perimenopausal patients (median age 42, range 25-55 years) with metastatic breast cancer were entered into an open phase II multicenter trial to evaluate efficacy of this new treatment modality. Patients were treated with the GnRH-analogue Goserelin (3.6 mg depot s.c. every 4 weeks) as first line therapy and followed up until progression. Mean serum gonadotrophins LH and FSH were significantly suppressed by Goserelin. Within 2-3 weeks, mean serum E2 values decreased to values seen in castrated women (less than 30 pg/ml). Overall objective response with complete and partial remissions (CR + PR) was achieved in 44.9% of patients with a median time to progression (mTTP) of 59 weeks, (range 20-163 weeks), no change (NC) in 28.0% with a mTPP of 27 weeks (range 16-101 weeks), and progression (P) in 27.1%. Responses were seen in ER-positive as well as ER-negative tumors, and in patients with different sites of metastases (locoregional, bone, visceral, multiple). The value of different prognostic factors in relation to response rates, time to progression and time to death (overall survival) is discussed. Median overall survival (time from beginning of palliative Goserelin treatment to death) was 148 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The depot GnRH analogue goserelin in the treatment of premenopausal patients with metastatic breast cancer--a 5-year experience and further endocrine therapies. Cooperative German Zoladex Study Group. 182 49

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

Hormonal changes induced by the pure antiandrogen flutamide were studied in three postmenopausal metastatic breast cancer patients. The drug was administered at a dose of 250 mg, three times a day for 3-6 months. In each patient a sharp decrease of about 50% was observed in the circulating levels of DHT and DHEAS, irrespective of pretreatment values. A concomitant, although less pronounced, reduction in circulating testosterone, androstenedione and estradiol was found. A decrease in circulating steroids was associated with a 30% decrease in SHBG concentrations in two patients; in the third patient a 30% increase occurred. Androgens in urine, namely testosterone, androstanediol and 17-KS, decreased accordingly. In addition, a marked decrease in 17-OHCS occurred in two of the patients. These data indicate that flutamide is an effective antiandrogen in women and suggest two possible mechanisms by which the drug exerts its antiandrogenic activity: (a) inhibition of conversion of testosterone into the more active DHT, and (b) inhibition of synthesis of the adrenal precursors of active androgens. Minor variations in circulating LH and FSH were observed. Pretreatment prolactin values, which were higher than normal, dramatically decreased by 90% in one patient who had a partial remission of her disease, and they further increased in another patient who relapsed while on therapy.
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PMID:Hormonal changes induced by the pure antiandrogen flutamide in postmenopausal women with advanced breast cancer. 297 45

Both medroxyprogesterone acetate (MPA) and megestrol acetate (MA) are effective in the treatment of metastatic breast cancer. Although the dose-dependent mode of actions of MPA have been extensively clarified, there is still some uncertainty regarding the mode of actions and dosage of MA. Thirty-three patients with metastatic breast cancer were treated with various dosages of MA under a phase-II study. Eight patients were given 200 mg, 9 X 400 mg, 10 X 600 mg and 6 X 800 mg MA daily per os. The LH, FSH, TBI, T3, T4, TSH, ACTH, aldosterone, testosterone, prolactin and cortisol levels were determined regularly during treatment to enable the investigation of the pharmacodynamics of MA. A complete remission was achieved in two patients, a partial remission in seven patients and there was no change in eight patients (total responder rate 51.5%). The clinical and endocrine changes therefore suggest that the dose-dependent mode of actions of MPA and MA are identical. Equivalent dosages of MPA are 1000-1500 mg per os and of MA 160-200 mg. Furthermore, similar relationships between the endocrine changes and remission behaviour of MA and MPA have been observed. Persisting tumour remissions are inevitable under cortisol suppression and normal prolactin, aldosterone and ACTH levels.
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PMID:[Megestrol acetate in various doses in the treatment of metastatic breast carcinoma--clinical and endocrinologic studies]. 298 1

We determined serum levels of estradiol, FSH and LH over a period of six to eight weeks after ovarian irradiation for castration with different doses (2 x 2.5 Gy/3 x 2.5 Gy/4 x 2.5 Gy) in 15 patients with metastatic breast cancer as compared to changes after ovariectomy in five patients. The time course of the changing estradiol-, FSH and LH-serum levels significantly depends on the ovarian dose. After radiological castration with a dose of 4 x 2.5 Gy = 10 Gy in four days the estrogen levels decrease within two to three weeks, and the FSH- and LH-levels increase after three to four weeks into the postmenopausal range. Therefore, the time course is not very different from changes after ovariectomy.
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PMID:[Changes in the serum level of female sex hormones following radiocastration using different total doses]. 312

Based upon preliminary observations that tumor response to MPA was correlated to cortisol suppression 42 patients were treated with MPA at different dose levels. 1500 mg MPA p.o. almost completely suppressed endogenous cortisol production in 23 out of 23 patients. Consequently, 51 patients with advanced stage metastatic breast cancer were treated with Medroxyprogesteroneacetate (HD-MAP) at a dosage of 1500 mg p.o. daily or 500 mg i.m. on 5 days per week. There were 5 complete and 7 partical remissions, 23 patients with no change and 10 with progressive disease. 7 patients were not evaluable. Clinical results correlated to plasma cortisol and prolactin blood levels bot not to LH, FSH, TSH, TBI, T3, T4, ACTH and aldosterone measurements. There was no patient with relapse and suppressed cortisol or normal prolactin measurements. The development of pituituary resistance to MPA is suggested. HD-MPA was equally effective in estrogen and/or progesterone receptor positive as in receptor negative patients. It is proposed that cortisol and prolactin determinations are useful to monitor for effective MPA treatment and the early detection of MPA resistance.
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PMID:[High dose medroxyprogesteroneacetate in metastasizing breast cancer: correlations between course of the disease and hormone profiles]. 622 46

The calcitonin-like immunoreactivity (CT-like immunoreactivity) was measured in blood aspirated from the vascular bed of the anterior pituitary gland during transsphenoidal surgery in 33 patients with PRL-producing microadenomas, 2 patients with Cushing's disease, and 1 patient with metastatic breast cancer with a normal pituitary gland. The mean level of CT-like immunoreactivity in the pituitary vascular bed was 2-3 times higher than in peripheral blood (2.4 +/- 0.9 ng/ml vs. 0.69 +/- 0.19 ng/ml), and the difference was highly significant (P less than 0.001). However, the serum ACTH, hGH, TSH, PRL, and FSH in the pituitary vascular bed was 1000 times or higher than that found in the peripheral blood. The serum CT-like immunoreactivity levels in the pituitary bed in the two patients with Cushing's disease were similar to that found in other patients. Our investigations indicate: 1) CT-like immunoreactivity in man is higher in the blood obtained from the pituitary vascular bed than that found in the peripheral blood; 2) the serum CT-like immunoreactivity level in the pituitary vascular bed is much less than ACTH or the other hormones secreted by the pituitary gland; 3) there is no correlation between CT-like immunoreactivity and ACTH levels.
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PMID:Calcitonin-like immunoreactivity in the pituitary vascular bed of man. 627 Jan 88

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


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