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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 antiestrogen employed frequently in the treatment of breast cancer. An association between this drug and endometrial neoplasia has been reported. We report on 11 postmenopausal women with breast cancer who developed endometrial cancer while undergoing tamoxifen therapy and recommend aggressive investigation of vaginal bleeding in all women being treated with this agent.
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PMID:Tamoxifen and endometrial cancer. 143 40

Tamoxifen, which is increasingly being used in breast cancer patients, has been associated with an elevated frequency of endometrial carcinoma. To our knowledge not a single case of uterine serous papillary carcinoma (USPC) has been documented during tamoxifen treatment. No conclusions as to a causal relationship are yet being made, but if it is due to tamoxifen, we should advise a strategy for prevention, because this subtype is not as curable as endometrioid carcinoma.
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PMID:An unusual type of endometrial cancer, related to tamoxifen? 145 92

Tamoxifen is a nonsteroidal antiestrogen that has found successful applications for each stage of breast cancer in the treatment of selected patients. Tamoxifen was originally introduced for the treatment of advanced disease in postmenopausal women; however, the drug is now also available for the palliative treatment of premenopausal women with estrogen receptor (ER) positive disease. The proven efficacy of tamoxifen and the low incidence of side effects made the drug an ideal agent to test as an adjuvant therapy for women with node-positive breast cancer. Laboratory studies indicate that long-term treatment schedules may provide maximal benefit in preventing recurrence, and recent analysis of clinical trials demonstrates that between 2 and 5 years of adjuvant tamoxifen therapy provides a survival advantage for postmenopausal women with node-positive disease. Similarly, adjuvant studies in node-negative breast cancer have demonstrated an increase in the disease-free survival of both pre- and postmenopausal patients with ER-positive tumors. However, the extended use of tamoxifen has raised questions about the long-term safety of antiestrogen therapy. Of special concern is the impact of tamoxifen on ovarian function in premenopausal women and the potential risks to the fetus if pregnancy occurs. Fortunately, there are no reports about the teratogenicity of tamoxifen in the human, but it is important that physicians counsel women about the risk of pregnancy. Tamoxifen should not be used if a patient is pregnant. Initial concerns that the long-term administration of an antiestrogen would increase bone loss and increase the risks of coronary heart disease appear to be unwarranted. Tamoxifen has some estrogen-like activities in postmenopausal women and causes a preservation of bone in the lumbar spine and a decrease in circulating cholesterol. Indeed, a reduction in fatal myocardial infarction (MI) has been noted during 5 years of tamoxifen therapy, possibly the direct result of a prolonged reduction in circulating cholesterol. However, the estrogen-like qualities of tamoxifen that could be valuable as a hormone replacement therapy for all postmenopausal women following a diagnosis of breast cancer may also increase the risk for developing endometrial carcinoma. To date, there are only a few reports of endometrial carcinoma being diagnosed during adjuvant therapy with tamoxifen; however, any instances of uterine bleeding or spotting should be followed up with an endometrial biopsy. There are some concerns about large doses of tamoxifen promoting liver cancer in rats. These results are of particular concern if tamoxifen is to be used as a preventive in normal women.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of tamoxifen in the treatment and prevention of breast cancer. 158 40

Tamoxifen is the most widely used non-steroidal antiestrogen compound for adjuvant treatment of postmenopausal breast cancer. Tamoxifen has both antiestrogen and estrogen-agonistic activity, which depends on the target tissue involved owing its systemic distribution. Upon the endometrium the agonistic estrogenic effect, so-called "paradoxical" effect, is suggested to induce proliferative changes such as hyperplasia or carcinoma. The authors report four cases of endometrial cancer developed in postmenopausal patients with breast cancer receiving tamoxifen. According to the literature data, the relationship of the tamoxifen to the endometrial remains uncertain: women with breast cancer are at increased risk for this neoplasm sharing common aetiologic hormonal factors and, in most published case reports, the uterine cavity has not been checked up before starting tamoxifen administration.
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PMID:[Cancer of the endometrium caused by antiestrogens]. 163 76

We previously demonstrated the estrogen-like effects of tamoxifen on the acceleration of growth and increased progesterone receptor concentrations of human endometrial carcinomas grown in the nude mouse experimental model. In our current study the modulation of protooncogene expression by 17 beta-estradiol and tamoxifen in human endometrial carcinomas was investigated. The protooncogenes investigated in this study were c-fos, c-jun, c-myc, N-myc, HER-2/neu, c-erbB, c-fms, and c-Ha-ras. Among those we found that c-fos expression was induced by 17 beta-estradiol in the following 17 beta-estradiol-sensitive tumors: EnCa-101 and EnCa-X. The induction was apparent within 1 hour, reached peak level at 2 hours (16-fold), and remained constant up to 4 hours. The c-fos messenger ribonucleic acid returned to prestimulation level by 12 hours. Tamoxifen also stimulated c-fos expression, the expression pattern being similar to that of 17 beta-estradiol albeit of a lesser degree. The messenger ribonucleic acid transcripts for other protooncogenes tested did not show significant changes during hormonal manipulation. The induction of c-fos expression by tamoxifen is consistent with its estrogen-like effect on endometrial carcinoma growth.
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PMID:Both 17 beta-estradiol and tamoxifen induce c-fos messenger ribonucleic acid expression in human endometrial carcinoma grown in nude mice. 128 91

Tamoxifen is an important agent for the treatment of breast cancer. Occasionally the drug, which is an antiestrogen, has agonistic estrogenic activity. The authors describe three new cases of endometrial carcinoma developing in breast cancer patients taking tamoxifen and stress the necessity of carefully monitoring the uterine cavity under tamoxifen treatment.
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PMID:Endometrial carcinoma in tamoxifen-treated breast cancer patients. 177 63

Tamoxifen (TXF), a triphenylethylene antiestrogen, is the major therapeutic agent for breast cancer. In rare cases, TXF treatment appears to increase incidence of endometrial cancer. Also in rats, TXF was found to induce hepatocellular carcinoma. Previous studies suggested that metabolism of TXF may contribute to its antiestrogenic and anticancer activity. The current study demonstrates a novel route of TXF metabolism. TXF is metabolized by rat and human liver microsomes into a reactive intermediate (txf*) which binds irreversibly to microsomal proteins. The binding requires NADPH and O2 and is inhibited by CO, inhibitors of P-450, and antibodies to rat NADPH-P450 reductase, indicating catalysis by P450. Phenobarbital treatment of rats markedly increases binding, suggesting the involvement of induced P450s. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins from incubation of [14C] TXF with phenobarbital-treated microsomes exhibits a major radiolabeled zone which corresponds to a molecular weight of approximately 54,000, suggesting binding to a P-450. Cysteine and glutathione inhibited the binding of TXF without significantly affecting P-450-mediated metabolism of TXF, possibly by reacting with txf* or by competing for the same binding sites. Exposure of phenobarbital-treated microsomes and control-microsomes to 50 degrees C for 90 s, which inactivates the flavin-containing monooxygenase (FMO), diminished binding and pH 8.6 enhanced binding. Also, alternate FMO substrates inhibited binding. These findings indicate that P-450 and possibly FMO catalyze the reactions leading to the formation of txf*. However, incubations with single-labeled and dual-radiolabeled tamoxifen or with [14C]TXF-N-oxide demonstrated that monodesmethyl-TXF and TXF-N-oxide, the principal P-450 and FMO-mediated metabolites, respectively, are not on the major route of txf* formation, indicating that txf* could not be an aldehyde derived from tamoxifen nitrone. Thus, though the structure of txf* was not characterized, certain possibilities were excluded. Speculations on the structure of txf* and on its possible pharmacological and toxicological activity are presented.
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PMID:Cytochrome P-450-mediated activation and irreversible binding of the antiestrogen tamoxifen to proteins in rat and human liver: possible involvement of flavin-containing monooxygenases in tamoxifen activation. 193 68

In a previous study we showed that endometrial carcinoma (EC) patients have a T cell deficiency manifested in a reduced ability to be stimulated in vitro by PHA and to produce IL-2. In an attempt to understand the mechanism responsible for this alteration we present in this paper a study on T cells characterized by the ability to form rosettes, with human erythrocytes, following Con-A activation (designated auto-rosette forming cells--ARFC). These cells are also known to manifest suppressive activity. We show that the frequency of ARFC in con-A activated peripheral blood leukocytes (PBMC) of EC patients is significantly (2-5 fold) higher than that of healthy age-matched controls or that of patients with stage--I colon or vaginal cancer. Endometrial carcinoma is known to be associated with long term exposure to estrogens unopposed by progestins. Examining the possible role of estrogens in increasing the frequency of ARFC from EC patients, we found that in vitro addition of estradiol to Con-A stimulated PBMC from healthy donors increased the frequency of ARFC to levels found in EC patients. Tamoxifen, an anti estrogen drug, reduced the frequency of the estrogen stimulated ARFC to the original low level. Our results suggest a dual role for estrogen in carcinogenesis as well as in immunomodulation.
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PMID:Frequency and activity of autorosette forming cells in Con-A activated PBL from women with hyperplasia or carcinoma of the endometrium--possible role of estrogens. 196 3

Tamoxifen is a widely used drug in medical oncology, mainly for treatment of breast cancer, but also for second line treatment of endometrial cancer. We recently reported an increased incidence of endometrial cancer associated with long-term adjuvant tamoxifen. This observation, previous reports of stimulatory effects of tamoxifen in the female genital tract, and experimental data are in accordance with a mainly estrogenic effect of tamoxifen in these tissues. An increased incidence of endometrial cancer may limit the usefulness of tamoxifen for benign indications. For adjuvant treatment of early breast cancer, however, the improvement of both recurrence-free survival and overall survival probably outweighs the increased frequency of uterine tumors. However, the possibility of growth stimulation of tumor subclones should be considered when tamoxifen is used in the treatment of endometrial cancer.
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PMID:Effects of tamoxifen on the female genital tract. 206 3

The results of preoperative use of oxyprogesterone caproate (OPC), Tamoxifen and their combination in 165 patients suffering from primary endometrial carcinoma are presented. It was shown that Tamoxifen was able to increase concentrations cytoplasmatic receptors to progesterone in the tumor. The incidence of specific hormonal pathomorphosis in the tissue of the tumor in patients who received a combination of OPC and Tamoxifen was significantly higher (80% of cases) as compared to the separate use of OPC (60%) or Tamoxifen (57%).
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PMID:Effect of oxyprogesterone caproate, tamoxifen and their combination on the level of steroid hormone receptors in the tumor, and some parameters of the reproductive system in patients with endometrial cancer. 212 40


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