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 was evaluated as initial hormone therapy for metastatic breast cancer in 85 premenopausal patients. Tamoxifen responders continued on tamoxifen, while tamoxifen failures and initial responders who later progressed were to receive ovarian ablation next. Of 74 evaluable patients, 5 had complete responses (CR) and 15 had partial responses (PR) while 12 remained stable (ST), giving response rates of 27% (CR + PR) or 43% (CR + PR + ST). Of the 23 patients who initially responded (CR + PR + ST) to tamoxifen but then progressed and received ovarian ablation alone, 15 are assessable. Nine (60%) responded (CR + PR + ST) to ovarian ablation. Sixteen patients who failed tamoxifen had ovarian ablation alone, and of 14 assessable patients 2 had ST while 12 progressed. Thus response to tamoxifen strongly predicted response to ovarian ablation (P = 0.021). Serial follicle stimulating hormone, prolactin, and estradiol levels suggested that tamoxifen does not act by induction of a "medical ovariectomy" or by alteration of prolactin levels in premenopausal patients.
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PMID:Role and mechanism of action of tamoxifen in premenopausal women with metastatic breast carcinoma. 308 82

Tamoxifen, an antiestrogen, is a competitive inhibitor of estradiol, blocking its effects on the target organs. During the 10 years it has been used in the United States it has become preferred over estrogens for treating postmenopausal women with metastatic breast cancer. Recently, tamoxifen has been used in treating premenopausal women with recurrent breast cancer, and its efficacy has been proved equal to that of ovarian ablation. In comparative trials, tamoxifen has been as effective as alternative endocrine treatments, and has greatly reduced toxicity and no irreversible side effects. Because of the high risk for systemic relapse in patients with breast cancer with regional lymph node metastases, (stage II), tamoxifen has been evaluated as adjuvant therapy after local treatment of the tumor. The results of these trials have shown a significant increase in the disease-free survival of postmenopausal women treated with tamoxifen, particularly in patients with hormone-receptor-positive tumors. Tamoxifen has not been as useful as adjuvant treatment in premenopausal women, for whom combination chemotherapy is the treatment of choice.
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PMID:Tamoxifen in the treatment of breast cancer. 329 59

Sixteen patients with clinically localized breast carcinoma who had been receiving tamoxifen 20 mg twice daily for between 3 and 38 months (median, 14 months) were studied. Several parameters of coagulation (antithrombin III, protein C, fibrinopeptide A and in vitro monocyte procoagulant activity) were investigated in this group and compared to a group of 15 patients with clinically localised breast carcinoma not given tamoxifen. Tamoxifen did not induce significant changes in these parameters to account for the reported thromboembolic events associated with this therapy. The reduced antithrombin III activity previously described in patients receiving tamoxifen for metastatic breast cancer may reflect disease activity rather than a direct effect of tamoxifen on blood coagulation.
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PMID:Effects of tamoxifen on blood coagulation. 334 87

Thirty-four postmenopausal patients with advanced breast cancer had an overall objective response rate of 47% when treated with aminoglutethimide and hydrocortisone initially and a response rate of 24% when crossed over to therapy with tamoxifen after progression on aminoglutethimide. A similar group of 32 patients experienced a response rate of 28% when treated with tamoxifen first and a 19% objective response rate on subsequent therapy with aminoglutethimide. Patients who failed to respond to the first therapy seldom responded on cross-over to the alternate therapy. Toxicities were acceptable with both forms of therapy. Tamoxifen and aminoglutethimide used sequentially are effective forms of palliative hormonal therapy in metastatic breast cancer.
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PMID:Cross-over comparison of tamoxifen and aminoglutethimide in advanced breast cancer. 617 5

Thirty-eight metastatic breast cancer patients were treated with aminoglutethimide. All patients had progressive metastatic disease following initial response to Tamoxifen therapy. Thirty-two patients were evaluable for response, of these, two patients (6%) had complete remission, 13 patients (41%) had partial response, and six patients (19%) had stable disease. Eleven patients (34%) had progressive disease. The most common side effects were transient skin rash, lethargy or dizziness. Four patients' (11%) treatment was discontinued because of either skin rash or dizziness within the first two weeks of the study. These data show that aminoglutethimide is an effective agent following tamoxifen therapy.
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PMID:Treatment of advanced breast cancer with aminoglutethimide after therapy with tamoxifen. 618 Aug 20

From June 1958 to June 1982, 22 men with metastatic breast cancer were treated with endocrine therapy. All 22 patients were initially treated by bilateral orchiectomy, and objective response was seen in 11 (50%) patients for 15 months. Bilateral adrenalectomy was performed subsequently in 10 patients, and 8 (80%) patients had a mean duration of objective response of 15 months. Five of seven orchiectomy responders and 3 of 3 orchiectomy nonresponders subsequently responded to bilateral adrenalectomy. Tamoxifen was tried in three patients after relapse following adrenalectomy; all three patients responded with a mean duration of 9 months. One patient was successfully treated with aminoglutethimide for 7 months following orchiectomy failure. In this patient bilateral adrenalectomy was performed on disease relapse and again resulted in objective remission. In this review, a sequential endocrine therapy program provided palliation in men. Further study is required to determine the timing of the various endocrine modalities.
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PMID:Metastatic breast cancer in males. Assessment of endocrine therapy. 619 69

A 44-year-old premenopausal woman with metastatic breast cancer to the bones was treated with tamoxifen and tegafur followed by a minimal dose of tamoxifen alone, with complete response for more than 90 months. Initially, tamoxifen was given with a dose of 20 mg daily in combination with 600 mg daily of tegafur for 22 months, a remission of low back pain and recalcification of the lytic lesion in the pelvis. After reduction of tamoxifen dose to 10 mg/daily and withdrawal of tegafur, regression of the disease continued for another 68+ months. Bone metastasis completely disappeared, and the patient is still in remission. No significant side effects from tamoxifen were encountered. Tamoxifen appears to be a useful and safe treatment for recurrent breast cancer.
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PMID:[A case of recurrent breast cancer responding to long-term administration of tamoxifen]. 643 1

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

Thirty-one of 62 consecutive premenopausal women with primary cancer of the breast completed a 1-year investigation period, receiving either 30 mg tamoxifen daily (15 patients) or placebo (16 patients). They were examined at the operation (t0) and at 3-month intervals (t1, t2, t3, and t4). Bone mineral content (BMC) was measured at operation and after 12 months. Fifty-six patients with benign tumors were included as healthy controls. All values of both cancer treatment groups and of the benign tumor group were comparable at the time of operation. BMC decreased significantly in both cancer patient groups when 12-month values were compared to the initial level (tamoxifen, -3.2%, P less than 0.001 and placebo -2.5%, P less than 0.01). However, no significant difference in BMC changes was noted between tamoxifen and placebo treatment. The serum phosphate was significantly decreased in the tamoxifen treatment group at each examination. In the placebo group, the alkaline phosphatase level increased significantly at each examination, whereas the serum magnesium fell at the 6- and 12-month examinations. All other biochemical indices of calcium metabolism were basically unchanged. It is concluded that BMC is reduced in metastatic breast cancer through osteolytic metastatic bone foci. Tamoxifen also decreases the BMC. It is, however, unclear if this effect is due to a progression of the disease in spite of the treatment or if it is caused by a direct action of tamoxifen on bone.
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PMID:The effect of tamoxifen on bone mineral content in premenopausal women with breast cancer. 669 87

Tamoxifen (T) was given in doses of 40-120 mg/day to 11 premenopausal women with stage IV breast cancer. Objective remission occurred in five, the disease did not progress in one, and five failed to respond. Duration of remission is 19+ months. Five patients underwent ovariectomy after receiving T: of two who responded to T and then relapsed, one responded to ovariectomy; three who failed to benefit from T also failed to improve after ovariectomy. The effect of T on the menstrual cycle ranged from no effect to complete cessation of menses, usually observed in patients who received larger doses. T induced a marked rise in serum estrone and estradiol, reaching levels up to 2500 pg/ml; serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels remained in the normal premenopausal range or were slightly elevated. In two patients in whom amenorrhea was induced with larger doses of T, both serum estrogen and gonadotropin levels were elevated. We conclude that T is effective in treating premenopausal patients with stage IV breast cancer. Because of the stimulating effect of T on ovarian function. escalated doses of T or castration plus T may be necessary in those patients who respond to T.
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PMID:Antiestrogen-induced remissions in premenopausal women with stage IV breast cancer: effects on ovarian function. 677 8


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