Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-two patients with metastatic melanoma received combination chemotherapy and hormonal therapy. Treatment included Carmustine, Cisplatin, Dacarbazine and Tamoxifen (BCDT). The overall response rate was 47%: five patients had a complete response (16%), 10 patients had a partial response (31%) and two had no response (6%). The median survival for responders was 10 months (range 2-20). The BCDT regimen was equally effective against soft tissue and visceral metastases. Neither survival or response rate was modified by pretreatment with alpha-interferon (alpha-IFN). In agreement with the results of a recent randomized trial comparing the efficacy of Dacarbazine with that of Dacarbazine plus Tamoxifen, a better survival was found in women than in men: although the response rate was identical (47%), the median duration of response was higher for women. A fall in serum soluble IL-2 receptor (sIL-2R) levels after therapy was seen in responding patients, confirming the usefulness of this parameter in monitoring disease evolution.
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PMID:Therapy for metastatic melanoma: effective combination of dacarbazine, carmustine, cisplatin and tamoxifen. 851 51

Tamoxifen, a non-steroid anti-oestrogen derivative of diethylstilboestrol, is the main drug used for hormone therapy for hormone-dependent breast cancer. This ambivalent drug has both antagonist and agonist effects. While tamoxifen blocks tumour growth it can also have an undesirable agonist effect on the genital tract. The uterus is a target organ for this paradoxical action due to proestrogenic stimulation of the endometrium and the myometrium. We observed eleven cases of uterine fibromyoma during treatment with tamoxifen which required hysterectomy due to increased tumour volume. The pathology report on the surgical specimens did not show any evidence of malignancy. Differential diagnosis is based on sarcomatous degeneration of the fibromyoma and presence of intra-myomatous metastases from the breast. Hysterectomy is indicated in menopaused patients with a symptomatic fibromyomatous uterus before starting long-term anti-oestrogen therapy for hormone-dependent breast cancer.
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PMID:[Expansive uterine myoma during tamoxifen therapy. 11 cases]. 854 98

Tamoxifen as adjuvant systemic treatment after first isolated locoregional recurrence of breast cancer has been shown to decrease the subsequent locoregional relapse rate, but it affects neither distant metastases nor survival. In metastatic disease, tamoxifen has not improved response when added to ablation of ovarian function. The cyclical sequential use of tamoxifen with megestrol acetate has not increased the response over tamoxifen alone. Aromatase inhibitors are an expanding field; formestane and vorozole are effective agents, and letrozole shows promise. In chemotherapy, major interest has focused on the use of taxoids, with high activity being reported for both paclitaxel and docetaxel, the latter being particularly effective as a second-line treatment. Reports continue to reaffirm the effectiveness of vinorelbine. The in vitro ability of quinidine to reverse resistance to anthracyclines has not been repeatable in a clinical setting. The evaluation of high-dose chemotherapy with bone marrow support continues to be explored, but this approach has thus far not been demonstrated to improve clinical outcome in advanced disease. The intra-arterial administration of chemotherapy appears to have a useful palliative role in selected patients with locoregional disease.
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PMID:Metastatic breast cancer. 854

Oestrogen levels play a major role in conditioning the rates of bone changes in women. Tamoxifen is a synthetic oestrogen antagonist commonly used as an adjuvant therapy for breast cancer. The goal of the present study was to study the amount and the elemental composition of bone minerals in the appedicular skeleton of women with breast cancer treated with adjuvant tamoxifen, as well as to investigate the possibility of increased risk for osteoporosis. Forty-two patients, aged 41-65 years, without skeletal metastases were studied. The mean duration of tamoxifen administration on a daily dose of 20 mg was 21 months (range 1-59 months). It was found that neither the amount of phosphorus in hands (HBP) nor forearm bone mineral content (BMC) differ statistically from those of age-matched healthy subjects. This was confirmed by reassessing bone mineral status after 30 months in 17 postmenopausal patients treated with tamoxifen for a mean time of 52 months. In conclusion, our data support that long-term tamoxifen treatment has no adverse or protective effect on the amount and elemental composition of the appedicular skeleton.
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PMID:Elemental composition of bone minerals in women with breast cancer treated with adjuvant tamoxifen. 875 May 83

Tamoxifen is useful in the treatment of breast cancer, but its effects in metastatic disease are rarely long term, and development of resistance to the drug is common. In vitro and in vivo data demonstrate anti-neoplastic (anti-proliferative) effects of somatostatin analogues, which may occur via binding to somatostatin receptors on the neoplastic cells, and/or via reductions in insulin-like growth factor-1 bioactivity. Moreover, several lines of evidence from in vitro and in vivo studies indicate that the long-acting somatostatin analogue octreotide enhances the anti-neoplastic effects of anti-oestrogenic agents such as tamoxifen. The anti-oestrogen-somatostatin approach appears to have a favourable long-term toxicity profile. Large-scale clinical trials are currently being planned to investigate the efficacy of combined tamoxifen plus octreotide therapy compared to tamoxifen alone in patients with breast cancer.
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PMID:Enhancement of the anti-neoplastic effects of tamoxifen by somatostatin analogues. 881 63

Hormonal agents play a critical role in the palliation of advanced breast cancer, as well as adjuvant therapy to surgery and radiation in patients with primary breast cancer. Tamoxifen appears to be the therapy of choice for the initial treatment of metastatic breast cancer in both premenopausal and postmenopausal women, although some clinicians prefer oophorectomy or the use of luteinizing hormone releasing hormone analogues in premenopausal patients. Historically, second-line hormonal therapy for metastatic disease has been with a progestin; however, due to the troubling side effects of weight gain and dyspnea, progestins may soon be replaced by aromatase inhibitors. The development of new antiestrogens lacking estrogen-agonist activity for metastatic disease is in its earliest clinical developmental phases. For adjuvant therapy in postmenopausal women, there is conflicting evidence as to whether the combination of a hormonal agent (ie, tamoxifen) plus chemotherapy provides an advantage over hormonal therapy alone. In premenopausal women areas of active investigation include combination hormonal therapy (eg, tamoxifen plus luteinizing hormone releasing hormone analogues or oophorectomy) and combination chemohormonal therapy (concomitant v sequential). Tamoxifen had been associated with rare cases of thromboembolic events and secondary endometrial cancers. The etiology of these secondary cancers is unclear and controversial; however, the benefits of tamoxifen far outweigh the risks for both palliative and surgical adjuvant therapy. The success of tamoxifen in preventing cancer recurrence in the contralateral breast has led to clinical investigation of the drug for the chemoprevention of breast cancer in women at high risk for development of the disease. The role of tamoxifen for this indication remains to be determined following completion of the National Surgical Adjuvant Breast and Bowel Project trial in North America and additional trials in the United Kingdom and Italy.
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PMID:Hormonal approaches to breast cancer treatment and prevention: an overview. 882 59

Tamoxifen (TAM) treatment following isolated locoregional recurrence of breast cancer significantly increases 5-year disease-free survival rates compared with observation alone in potentially hormone-responsive patients [J Clin Oncol 1994, 12, 2071-2077]. The treatment outcome was re-analysed by menopausal status (stratification factor) in 35 premenopausal and in 132 postmenopausal patients. Disease progression was highly reduced by tamoxifen in the postmenopausal group and was similar to control in the premenopausal group. However, the 5-year cumulative incidence analysis of the type of first failure showed TAM to be associated with increased incidence of distant metastases (P = 0.01) in premenopausal patients. TAM reduced local progression (P = 0.40) in premenopausal and both types of failure (P = 0.16 and P = 0.001, respectively) in postmenopausal patients. Administration of TAM was associated with a decrease of 5-year overall survival from 90 +/- 7% to 60 +/- 14% in premenopausal patients. Although cautious interpretation of these results is highly recommended due to the small patient numbers and the retrospective subset analyses, these findings might be worthy of further investigation in larger trials. Prospective randomised studies to test hormonal treatment outcome by menopausal status should be encouraged in breast cancer.
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PMID:Possible deleterious effect of tamoxifen in premenopausal women with locoregional recurrence of breast cancer. 901 62

Breast cancer treatment has evolved greatly within the last 25 years. Tamoxifen was first introduced for the treatment of metastatic breast cancer in the 1970s and later became accepted as standard adjuvant therapy. The emergence of tamoxifen as first-line hormonal therapy for metastatic disease and in the adjuvant setting occurred due to its efficacy in achieving prolonged overall survival as well as improved disease-free survival, the latter of which improves the psychological and physical quality of life of the patient. Tamoxifen is currently being studied for the prevention of breast cancer. Completion of this important trial is eagerly awaited.
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PMID:Tamoxifen's impact on the management of breast cancer: the oncologist's perspective. 906 28

Tamoxifen (TAM) is widely used as therapy in early breast cancer and first-line endocrine therapy in metastatic disease. Despite this therapy, many patients relapse and an important question is: What is the preferred sequence of endocrine therapies in metastatic breast cancer (MBC). While treatment with oophorectomy, aminoglutethimide or progestins have been a logical choice after failure to Tamoxifen recent research has extended the options for endocrine therapy of MBC. New selective aromatase inhibitors (AI) are now in clinical use. The first commercially available of these inhibitors is LENTARON. The active ingredient of LENTARON is a steroidal compound 4-OH-androstenedione: Formestane. It is presented as a depot formulation and applied as an i.m. injection of 250 mg every second week. Previous findings from phase II trials have indicated similar activity as other endocrine treatment modalities. Clinical investigations in properly conducted phase III trials have revealed that the efficacy of LENTARON matches the results which can be obtained with TAM and Megace in trials of first and second-line endocrine therapy. Fifty-four and 51% of MBC patients, respectively, did benefit from therapy with LENTARON in these phase III trials by achieving objective responses or stable disease. Moreover, similar overall survival was seen. The systemic tolerability of LENTARON is comparable to that of TAM, and LENTARON seems less systemically toxic than Megace. Local side effects occured in approximately 7% of the patients giving rise mainly to pain or inflammation at the injection site. In elderly patients, LENTARON therapy assures compliance and no interference with other oral medications has been observed. In conclusion, since the endocrine treatment modalities are comparable in terms of efficacy the optimal sequence of these treatments is based upon differences in tolerability. Patients previously treated with Tamoxifen and with a high probability of a further endocrine response could preferably be treated with a selective AI like LENTARON as second-line endocrine therapy followed by a progestin upon progression in responders.
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PMID:Proper sequence of endocrine therapies in advanced breast cancer. 914 64

We used enzymatic activity and immunochemical quantifications to analyse the expression and secretion of cathepsin D by human breast cancer cell lines of different invasive potentials (MCF-7/6, MCF-7/AZ, MDA-MB-231). This study does not directly prove that cathepsin D or procathepsin D is involved in human breast cancer cell invasion and metastasis but it shows that the proportion of procathepsin D (activity and antigen) secreted by the human breast cancer cell lines tested correlates with their invasive potential. In the estrogen receptor-positive MCF-7 subclones, this proportion is increased by estradiol only in the invasive MCF-7/6 variant. The cell content in procathepsin D is increased by estrogens to a greater extent in MCF-7/6 cells as compared to non-invasive MCF-7/AZ cells. Tamoxifen appears to be an estrogen agonist concerning cathepsin D regulation, whereas ICI 182,780 is a true antagonist. Our results suggest that synthesis and secretion of cathepsin D are regulated at two distinct levels and differentially affected by estrogens. Synthesis only seems to be affected in non-invasive MCF-7/AZ cells, whereas in invasive MCF-7/6 cells, both synthesis and the efficiency of secretion are increased by estrogens. Our results also confirm that the key site of regulation leading to lysosomal enzyme oversecretion is the Golgi apparatus insulin-like growth factor-II/mannose 6-phosphate receptor.
Clin Exp Metastasis 1997 Jul
PMID:Western immunoblotting and enzymatic activity analysis of cathepsin D in human breast cancer cell lines of different invasive potential. Regulation by 17beta-estradiol, tamoxifen and ICI 182,780. 921 23


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