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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A reassessment of the risks of using oral contraceptives regarding cancer of the cervix, endometrium, ovary, breast and biliary system was commissioned in the form of a series of reviews, published in the journal Contraception, June 1991: this is the introduction to the reports. Since 1977, the risks of developing epithelial ovarian cancer and endometrial cancer have been clearly shown to be reduced and that protection persists for years even in ex-pill users. The chance of getting hepatocellular carcinoma is slightly higher in developed countries, still extremely rare; while not noticeably increased in those developing countries that have high liver cancer rates. The likelihood of getting cervical cancer is increased in some studies but not in others, reflecting the difficult problem of controlling of patterns of sexual behavior in this area. Even though broad analyses of breast cancer risks are reassuring, some detailed studies that focus on certain age groups of women do find increased breast cancer. A special multi-center, hospital-based, case-control study in developing countries, sponsored by WHO, concluded that the results of studies on cancer from developing countries are applicable to developing countries as well. So the overall benefits of using oral contraceptives outweigh the risks, both for women in areas where maternal morbidity and mortality are high, because of the effectiveness of the pill in preventing pregnancy; and in industrialized areas, where the benefits of preventing ovarian cancer alone is enough to make pill use safer than other methods, such as the condom. There appears to be no way to predict cancer risks for any subgroup of women who should avoid taking the pill.
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PMID:Oral contraceptives and neoplasia: an introduction. 186 31

Oestrogens are administered to women as contraceptive agents and as treatment for menopausal symptoms. This article reviews the epidemiological evidence concerning the risk of breast cancer related to both types of medication. It is generally accepted that long-term; high-dose menopausal oestrogen administration without accompanying progestogen is associated with a moderate increase in breast cancer risk; and that combined oral contraceptives reduce the risk of benign breast disease (as well as ovarian and endometrial cancer). The effect of oral contraceptives on breast cancer risk, however, is less certain. Possible reasons for the lack of agreement between recently conducted case-control studies are discussed, concentrating specifically on the effect of possible latency, being the sum of a prolonged induction plus pre-clinical period, in explaining the discrepancies.
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PMID:Oestrogens and breast cancer: exogenous hormones. 193 28

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

This review covers the epidemiology of benign and neoplastic breast disease, the theoretical effects of steroids on the breast, and the effects of oral contraceptives on both. Breast cancer has been increasing since the 1940s in older U.S. women, killing about 44,500 of the 175,000 new cases per year. In addition fibrocystic breast disease may affect up to 50% of premenopausal women, resulting in 500,000 biopsies, of which 10% are cancerous, 33% of those in post-menopausal women. The involvement of steroids in development of the human breast, and in breast cancer, is reviewed. The breast does not complete its development until the end of the 1st pregnancy. The terminal ductal cells, from which breast cancers form, are susceptible to stimulation by progestins in nulliparas. Progestins, at least in the high doses used in early orals, protect against benign breast disease. Inadequate amounts of progesterone, however, as in irregular cycles, seem to predispose to breast cancer. Epidemiologic studies of oral contraceptive use and breast cancer are reviewed under the studies of oral contraceptive use and breast cancer are reviewed under the headings of overall results, age, age 45, parity, use before 1st pregnancy, use at young ages, latent effect, hormone formulation, associated benign breast disease, association with other neoplasms, and receptor status. There are slightly increased risks for cancer before age 45 for long-term use of pills before the 1st term pregnancy, although the data are not wholly consistent, in that the specific sub-groups of women affected differ in different studies. There is no clear evidence for a latent effect, that is, appearance of cancer 20-30 years after stopping the pill. Nor is there evidence of breast cancer linked to any specific pill type, nor with benign breast disease, nor with endometrial cancer. The reason for rising breast cancer rates is still unknown. The absolute number of increased cases related to oral contraceptives is insufficient to affect national rates. It is possible that the inconsistent findings in epidemiological studies reflects use of high-dose pills in the 1960s and early 1970s. The contraceptive and non-contraceptive benefits of the pill are more important for women's health than the potential cases of breast cancer in young women who took them for prolonged durations.
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PMID:Oral contraceptives and breast disease. 193 11

There is increasing awareness that the long-term consequences of ovarian failure can be prevented or reduced with appropriate hormone replacement therapy (HRT). After the menopause, there is a rapid loss of trabecular bone resulting in a one in two lifetime risk of osteoporotic fracture. HRT prevents this bone loss and decreases the incidence of fracture. A minimum of 5 years treatment is recommended for significant benefit. Epidemiological evidence is accumulating that post-menopausal oestrogen therapy reduces the risk of cardiovascular disease and stroke by between 30 and 70% even in the presence of established risk factors. Given the prevalence of cardiovascular disease, this is likely to be one of the principle benefits of HRT in the next decade. Concerns about the long-term safety of HRT have focused on endometrial and breast cancer. The increase in risk of endometrial cancer associated with oestrogen only therapy is abolished with the sequential addition of a progestogen for 10-12 days each cycle. The possible effect of HRT on breast cancer risk has to be considered against the background of a one in 12 lifetime risk of developing this disease. The epidemiological studies investigating this relationship are reviewed in this paper. There is a broad consensus that 5-6 years duration of HRT does not increase breast cancer risk. Longer durations of therapy (10-15 years) have been reported to increase this risk although not all the data are in agreement. Other factors, such as family history and benign breast disease, may also influence the risk of breast cancer. The potential benefits of HRT on mortality and morbidity are enormous. Against this is a possible small increase in breast cancer risk with long-term usage. Greater awareness of the long term consequences of the menopause and the potential benefits of HRT should be encouraged so that women can make informed decisions about their need for HRT.
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PMID:The long-term risks and benefits of hormone replacement therapy. 193 2

As part of a multi-centre epidemiological study of cancer in women between the ages of 20 and 54, data were collected concerning family history of gynaecological cancers in the female relatives of 4730 women with newly diagnosed breast cancer and the relatives of 4688 women from the general population. Women who were diagnosed with breast cancer prior to age 45 were more likely than controls to have a mother or sister with ovarian cancer (odds ratio (OR): 1.50), endometrial cancer (1.29), and cervical cancer (1.53), although none of these elevations achieved statistical significance. The corresponding odds ratios for women diagnosed with breast cancer between the ages of 45 and 54 were 1.88, 0.84 and 0.93. The association with ovarian cancer was statistically significant in this group (95% confidence interval (CI): 1.11-3.19). In this latter group, having a first degree relative with ovarian cancer was associated approximately as strongly with breast cancer as was having a first degree relative with breast cancer. The results suggest that there may be a shared genetic basis for some cancers of the breast and ovary. From a clinical perspective, the results indicate that in setting appropriate levels of screening for breast cancer and in establishing an appropriate age at which to begin such screening for a particular woman, her family history of ovarian cancer should be considered in addition to her family history of breast cancer.
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PMID:Family history of gynaecological cancers: relationships to the incidence of breast cancer prior to age 55. 195 42

The cathepsin D gene is differentially regulated by estrogens in hormone responsive breast cancer cells, by progestins in normal human endometrium and is highly expressed but not regulated by these steroids in estrogen (RE)- and progesterone receptor (RP)-negative breast cancer cells. We have stably transfected the RE-negative breast cancer cell line MDA-MB 231 and the Hela cell line with an expression vector for the human RE. The endogenous cathepsin D which is constitutively expressed was further stimulated by estradiol. However, the growth of both cell lines was not stimulated by estradiol and could not be inhibited by the antiestrogen ICI 164,384. By contrast, the cathepsin D gene in the estrogen responsive Ishikawa endometrial cancer cell line was unresponsive to estrogen or to progesterone even following stable transfection of expression vectors for the RP (both A and B isoforms). We conclude that the cathepsin D gene is potentially responsive to estrogens in MDA-MB 231 and Hela cells, which therefore express all of the transcriptional machinery (except the RE) necessary for this regulation. By contrast, cathepsin D remains unresponsive to estrogen and progesterone in Ishikawa cells. The cathepsin D gene is one of the first examples of an endogenous steroid responsive gene which can be controlled by steroids following stable transfection of a steroid receptor.
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PMID:Hormonal regulation of cathepsin D following transfection of the estrogen or progesterone receptor into three sex steroid hormone resistant cancer cell lines. 195 26

Recent experimental work has identified a novel intracellular binding site for the synthetic progestin, Gestodene, that appears to be uniquely expressed in human breast cancer cells. Gestodene is shown here to inhibit the growth of human breast cancer cells in a dose-dependent fashion, but has no effect on endocrine-responsive human endometrial cancer cells. Gestodene induced a 90-fold increase in the secretion of transforming growth factor-beta (TGF-beta) by T47D human breast cancer cells. Other synthetic progestins had no effect, indicating that this induction is mediated by the novel Gestodene binding site and not by the conventional progesterone receptor. Furthermore, in four breast cancer cell lines, the extent of induction of TGF-beta correlated with intracellular levels of Gestodene binding site. No induction of TGF-beta was observed with the endometrial cancer line, HECl-B, which lacks the Gestodene binding site, but which expresses high levels of progesterone receptor. The inhibition of growth of T47D cells by Gestodene is partly reversible by a polyclonal antiserum to TGF-beta. These data indicate that the growth-inhibitory action of Gestodene may be mediated in part by an autocrine induction of TGF-beta.
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PMID:The growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor beta. 198 2

The benefits of estrogen replacement therapy in preventing vasomotor symptoms, osteoporosis, and cardiovascular disease are well documented. Although estrogen is said to be contraindicated in patients successfully treated for endometrial and breast cancer, there are no data to substantiate this admonition. Experience suggests that it can be used safely in patients treated previously for endometrial cancer. Although there is little or no experience with estrogen use in the woman treated previously for breast cancer, circumstantial evidence suggests that it is not contraindicated in all such cases. Informed consent, patient desires, and risk-benefit considerations must enter into the decision to use estrogen in these patients.
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PMID:Estrogen replacement therapy: is previously treated cancer a contraindication? 198 99

Some endometrial cancers and endometrial adenocarcinoma cell lines show amplified expression of proto-oncogenes (fos, fms, myc, myb, neu, and erb-B) and augmented production of growth factors (colony-stimulating factor 1, epidermal growth factor, transforming growth factor-alpha, and transforming growth factor beta) and epidermal growth factor receptor. Oncogene expression, the presence of estrogen and progesterone receptors, and the fraction of cells in S phase are useful biochemical prognostic indicators of clinical outcome, and markers recognized by monoclonal antibodies are available for use in following the clinical course of the disease and responses to treatment. In vivo and in vitro studies on normal and neoplastic tissues are providing evidence of paracrine influences on epithelial cell proliferation. Long-term administration of tamoxifen as adjuvant therapy for breast cancer has recently been found to increase the risk for development of endometrial cancer.
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PMID:Endometrial cancer: biochemical and clinical correlates. 199 48


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