Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tamoxifen is a nonsteroidal anti-estrogen frequently used in breast cancer therapy. Side effects to tamoxifen are uncommon (2%) but should be recognized and detected early by careful follow-up. Tamoxifen adjuvant therapy is absolutely indicated in postmenopausal breast cancer with estrogen-receptor--positive nodes. Recently, this indication has been extended to negative-node postmenopausal breast cancer. Mild acute side effects are the most frequent: hot flushes, menstrual irregularity, nausea, headache, vertigo, minimal modifications in blood cell counts. However, more serious accidents can occur. Increased risk of thromboembolism is linked to a fall in the level of antithrombin III. Ocular toxicity can occur. If such ocular lesions are diagnosed early enough, they can be cured by promptly withdrawing treatment. For patients given tamoxifen, there appears to be a small increase in risk of endometrial carcinoma, especially if the daily dose is > 30 mg. This over-risk requires adequate detection based on sufficient knowledge of the usual tamoxifen-related modifications in the endometrium. Physicians should also be aware of two favorable effects. Tamoxifen therapy leads to decreased cardiovascular morbidity and mortality in postmenopausal women and is associated with a significant increase in lumbar bone density. Risk of interaction with oral anticoagulants has been reported. We discuss here practical steps in the follow-up of women treated with tamoxifen.
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PMID:[Surveillance of patients treated with tamoxifen]. 868 11

In 1985 a second randomisation was initiated for women in the treatment arm of the Scottish Tamoxifen Trial either to stop tamoxifen at 5 years or to continue indefinitely. A preliminary analysis of outcome in 342 patients at a median follow-up of 6 years suggests that a worthwhile gain in disease control from continuing adjuvant tamoxifen beyond 5 years is unlikely. [Hazard ratio for events (relapse or death without relapse) is 1.27, 95% CI = 0.87 - 1.85.] There is a suggestion that therapy for longer than 5 years may increase the risk of endometrial carcinoma (P = 0.064).
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PMID:Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. The Scottish Cancer Trials Breast Group. 868 40

Tamoxifen is an oestrogen antagonist with partial agonistic effects that is used extensively in the treatment of mammary carcinoma. We report a case of an 80 year old woman who was operated on for carcinoma of the mammary gland and developed endometrial carcinoma after ten years of tamoxifen treatment. Tamoxifen has been noted for its reportedly low incidence of side effects. Since 1985, however, several reports have associated tamoxifen with higher risk of endometrial carcinoma. We also review the relevant literature published during the last decade.
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PMID:[Tamoxifen and endometrial cancer. A case report]. 871 96

Tamoxifen (Nolvadex), a nonsteroidal antiestrogen, was first approved by the FDA for the treatment of patients with breast cancer in 1978. Large clinical trials have demonstrated a recurrence-free and overall survival benefit in both pre- and postmenopausal women. Long-term adjuvant tamoxifen is the endocrine treatment of choice for selected patients with breast cancer, and large-scale trials are currently underway to evaluate its role as a chemopreventive agent in healthy women at risk for breast cancer. Consequently, a large number of women will be subjected to both the benefits and potential risks of long-term tamoxifen therapy. One of the most significant potential complications is the development of endometrial cancer. The estimated annual risk of endometrial cancer in tamoxifen-treated patients is approximately 2 per 1,000 women. Most of these cancers will be detected at an early stage when they are highly curable. The potential benefit of tamoxifen treatment in breast cancer patients outweighs this risk; however, all patients receiving tamoxifen should undergo regular gynecologic evaluations.
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PMID:The effect of tamoxifen on the endometrium. 877 Oct 96

The involvement of the IGF system in the growth regulation of hormone-dependent (e.g. endometrial and breast) cancer cells was studied. We chose two opposing effects of tamoxifen: the paradoxical stimulation of Ishikawa endometrial cancer cells growth and its inhibitory effect on MCF-7 mammary cancer cells. The results clearly confirm our working hypothesis that the IGF system is involved in growth regulation of these cancer cells irrespective of the direction of the drug effect. The following parameters of the IGFs system were studied: IGF-I receptors, IGF-I stimulated protein tyrosine phosphorylation, and membrane-associated and secreted IGF-binding proteins (IGFBPs). In Ishikawa cells, tamoxifen, similar to estradiol, increased IGF-I stimulated tyrosine phosphorylation of cellular substrates in accordance with its effect on cell growth. This effect of tamoxifen was inverted in MCF-7 cells. Tamoxifen did not affect the number or affinity of IGF-I receptors in both Ishikawa and MCF-7 cells, however, it caused a three-fold decrease in membrane-associated IGFBPs in the endometrial cells but an increase in these proteins in breast cancer cells. Similar but much less pronounced changes in soluble IGFBPs were observed. Our results indicate that the opposing growth effects of tamoxifen an endometrial and mammary cancer cells are associated with modulation of the IGF system components, mainly with reciprocal changes in membrane-associated IGFBPs.
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PMID:Components of the IGF system mediate the opposing effects of tamoxifen on endometrial and breast cancer cell growth. 881 96

The main adverse effects of tamoxifen, aspirin, oral contraceptives (OCs) and retinoids used as chemopreventive agents in humans are reviewed and quantified here. With regard to tamoxifen, there are suggestions of some excess risk of liver, and perhaps gastrointestinal, cancers. The public health impact of such associations, if any, is still unclear. Tamoxifen use is associated with endometrial and myometrial hyperplasia. Data from five studies based on 174 cases indicate that the overall relative risk (RR) of endometrial cancer in ever tamoxifen users is 1.73 (95% confidence interval = 1.1-2.6). However, there is a significant difference between the results of American and European studies, so the relationship between tamoxifen and endometrial cancer remains open to debate. The major side-effect of aspirin is gastrointestinal lesions; the risk of these is increased two- to tenfold, depending on the dose. Aspirin is also associated with an increased risk of haemorrhagic stroke, although its protection against other types of stroke and against myocardial infarction leads to a favourable pattern of risk for all cardiovascular conditions. Short-term side-effects of OCs include vascular diseases and a moderately increased risk of breast cancer. The RR of cervical cancer and hepatocellular carcinoma are also increased in OC users, although the public health impact of such associations is small. Toxicity associated with retinoid treatment is rarely serious as most effects observed are reversible on stopping use. Side-effects include changes in the skin and mucous membranes (dry skin, hair loss, dry nose, conjunctivitis), musculoskeletal symptoms, ophthalmological effects, changes in transaminase activity, changes in clinical chemistry markers (increase in serum triglycerides and decrease in high-density lipoproteins) and, rarely, central nervous system effects. A serious toxicological aspect of retinoid treatment is teratogenesis; its use should therefore be avoided in women with childbearing potential, and, in cases of use, conception should be delayed for a long time after stopping treatment. Thus, when considering side-effects of chemoprevention, the major issues of concern are the rare long-term effects (chiefly neoplasms), and the need for more precise overall risk-and cost-benefit assessment, particularly for healthy people.
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PMID:Adverse effects of preventive therapy in humans. 892 25

Tamoxifen is a synthetic antiestrogen with both agonist and antagonist properties. It is believed to act primarily through binding to estrogen receptors in breast cancer cells, acting as a competitive inhibitor of estrogen. Tamoxifen has a wide range of systemic effects, possibly acting on every estrogen target tissue in the body. Tamoxifen therapy is associated with a significant reduction in the risk of recurrence and death in postmenopausal women with early stage breast cancer. In addition, it has been shown to effectively suppress preclinical breast cancer, as evidenced by the decrease in second primary breast cancers in adjuvant trials. Tamoxifen is also the most widely used endocrine therapy for women with metastatic breast cancer. Tamoxifen, acting predominantly as an estrogen agonist in the liver, has generally favourable effects on serum lipids in postmenopausal women. In addition, tamoxifen has been shown to preserve bone mineral density and may even decrease the risk of osteoporosis in these women. Most patients treated with tamoxifen have minimal adverse effects. Vasomotor symptoms are the most commonly reported events. Less frequently, vaginal discharge or dryness, nausea and depression have been reported. A slight increase in thromboembolic events in postmenopausal women taking tamoxifen has been suggested in some adjuvant trials. Rarely, ocular toxicity and hepatotoxicity are found. The adverse effect of primary importance is the increased incidence of endometrial carcinoma. Several studies indicate that almost all of the tumours are of low histological grade and stage, similar to those seen with exogenous estrogen use. The relative risk of endometrial cancer in women taking tamoxifen is about 2 to 4 times higher than for postmenopausal women not taking tamoxifen. The benefits of tamoxifen outweigh the risks in almost all postmenopausal women with estrogen receptor-positive early stage breast cancer and in all women with metastatic breast cancer. Should tamoxifen prove to be an effective chemopreventive agent for breast cancer, the risks and benefits of treatment will have to be more carefully assessed for this setting.
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PMID:Tamoxifen in postmenopausal women a safety perspective. 893 95

Tamoxifen is a widely used, effective, and well-tolerated agent in the treatment of primary and recurrent breast cancer. In the adjuvant setting, tamoxifen decreases the annual odds of recurrence and death by 25% and 16%, respectively. The toxicities of tamoxifen are of minor concern in the poor-prognosis group of women with metastatic breast cancer. In the more favorable group of women with early breast cancer, the benefits of tamoxifen appear to substantially outweigh the known toxicities. In retrospective analysis, tamoxifen has been consistently demonstrated to decrease the occurrence of contralateral second breast cancer and to be associated with an increased frequency of diagnosis of endometrial carcinoma. It is not known whether tamoxifen is promoting the growth of pre-existing, clinically occult endometrial carcinomas or is truly etiologic for the development of new cancers. The endometrial carcinomas that are associated with tamoxifen appear to have a biology and natural history similar to non-tamoxifen-associated endometrial carcinomas. There is no evidence supporting an association between hepatocellular carcinomas and tamoxifen in humans. Retrospective analysis of the association of colorectal carcinoma and gastric carcinoma provides little convincing evidence of a causal relationship, although further study is warranted.
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PMID:Scientific review of tamoxifen. Overview from a medical oncologist. 904 12

Tamoxifen has been used most commonly to treat breast and endometrial cancer, two malignancies in which the antiestrogenic properties of tamoxifen have substantial therapeutic benefit. However, tamoxifen has been used in the treatment of other cancers as well, some in which an antiestrogen may be effective, but others in which estrogen receptor is not expressed. In estrogen receptor-negative cancers, tamoxifen has been shown to have therapeutic activity at doses approximately fourfold to eightfold above those used for estrogen receptor inhibition. It is thought that the primary mechanism of tamoxifen in estrogen-negative tumors is inhibition of protein kinase C. Clinical trials of tamoxifen in ovarian cancer, hepatocellular carcinoma, desmoid tumors, malignant glioma, pancreatic carcinoma, melanoma, and renal cell carcinoma are reviewed.
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PMID:Tamoxifen for the treatment of malignancies other than breast and endometrial carcinoma. 904 18

Heat shock, other environmental and pathophysiological stress stimulate synthesis of heat shock proteins (HSP) family. These proteins enable the cell to survive and recover from stressful conditions but as yet incompletely understood mechanisms. Beside its role in thermotolerance, it plays a role in cell proliferation and drug resistance which makes this protein of special clinical interest. Published data suggest that HSP27 is related to estrogen in breast and to estrogen and progesterone in the endometrium. It has been shown that some but not all estrogen positive breast cancers express HSP27, and overexpression has been associated with the degree of tumor differentiation, and response to hormonal therapy (Tamoxifen). In endometrial carcinomas, the presence of HSP27 is correlated with the degree of tumor differentiation as well as with the presence of oestrogen and progesterone receptors. Studies suggest that detection of HSP27 in endometrial carcinoma, should not be considered as a method for identifying hormone-responsive tumors or indicator or presence of estradiol receptors. In the cervix HSP27 is a marker of cell differentiation, and is highly expressed during the process of squamous metaplasia. Expression in the ovary is still controversial and requires further confirmation of recent observations.
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PMID:Heat-shock protein 27 (HSP27) and its role in female reproductive organs. 906 15


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