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)

The development of tamoxifen therapy to treat selected patients, with all stages of breast cancer, has provided the clinical community with an efficacious and safe drug for long-term therapy. Issues of safety are under constant review, but justified concerns about high doses of tamoxifen acting as a promoter of liver cancer in rats or as a promoter of endometrial cancer in women have not, as yet, proved to be of clinical relevance. The situation will continue to be reviewed during the development of the prevention studies in Europe and the United States because an improvement in women's health is the ultimate goal of these programs. The hallmark for the successful development of tamoxifen has been the close cooperation between the laboratory and the clinic. The clinical strategy of long-term tamoxifen therapy is a direct application of a laboratory concept. Furthermore, potential problems in the clinic have been identified in the laboratory, and the clinical community has responded quickly to evaluate the real risks to the patient population. This close cooperation will continue. Issues of drug resistance, new antiestrogen development, and the application of the knowledge about steroid receptors to develop targeted gene therapies are being addressed so that additional treatment approaches for breast cancer will be in place by the turn of the century.
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PMID:Overview from the International Conference on Long-Term Tamoxifen Therapy for Breast Cancer. 134 4

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

Studies show that OCs have several benefits besides prevention of pregnancy. They protect against ovarian and endometrial cancer, pelvic inflammatory disease, and ectopic pregnancy. OCs also prevent iron deficiency anemia, primary dysmenorrhea, functional ovarian cysts, and benign breast disease. They may even protect against some benign uterine tumors, osteoporosis, toxic shock syndrome, and rheumatoid arthritis. Despite many concerns, some large studies have not identified an overall effect of OCs on breast cancer, but subgroup analyses showed increased risk in 30-34 year old women and in women with 1 child. A reanalysis of a large US study indicated an increase risk of breast cancer in nulliparous women with increasing use of OCs by young women. Cervical cancer is the leading cancer of women in developing countries which emphasizes the need to examine the link between OC use and cervical cancer. Several studies show an increased risk of cervical cancer. Several studies show an increased risk of cervical cancer in long term OC users. In 1 study, long term use meant 5 years. Yet these studies did not adequately address confounding factors such as smoking and sexual behavior. 3 case control studies in the US and the UK found an increased risk of liver cancer among OC users, yet a large case control study in developing countries did not find a link between OC use and liver cancer. Studies of high dose OCs found considerable increased risks of cardiovascular disease in OC users, but they did not take into account cigarette smoking which indeed increases the risk. Further health practitioners today do a more thorough job of identifying underlying medical problems before prescribing OCs. Moreover estrogen doses have fallen 10 fold since the original OCs. Finally, despite a transient delay, women who take OCs experience a return to fertility at the same rate as those who use other contraceptives.
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PMID:The safety of oral contraceptives: epidemiologic insights from the first 30 years. 160 84

Since hormones relate to the etiology of breast cancer, 40 studies have looked at the possible association of oral contraceptives (OCs) with breast cancer. Most research conducted through 1986 and including the largest related case control study and several after 1986 found no association between ever use of OCs and breast cancer. On the other hand, some studies conducted after 1986 with women 45 years old who had breast cancer and had taken OCs have suggested a dose response relationship, 2 fold increased risk of breast cancer, or increased risk with duration of OC use. These results motivated several organizations to review the literature and to issue guidelines. The US Food and Drug Administration, the UK Committee on the Safety of Medicines, and IPPF did not find a reason to change practices. The Committee on the Safety of Medicines did suggest, however, that health providers mention the possible increase in risk. At least 8 studies have revealed an increased risk of cervical cancer with duration of OC use, especially after 5 years of use. Yet experience has disclosed an obstacle to understanding the relationship between cervical cancer and OC use--cervical cancer may be caused by the human papilloma virus transmitted by sexual intercourse. Unlike results of breast and cervical cancer research, research results have clearly established that OC use lowers the risk of endometrial cancer by about 50% and the risk of ovarian cancer by about 40%. In fact, the US Cancer and Steroid Hormone [CASH] study showed a protective effect of OCs for endometrial and ovarian cancers at least 15 years after discontinuation. Even though some studies found a dose response effect with duration of use, a large international study did not find any relationship between OC us and liver cancer. Moreover studies did not reveal an association between OC use and malignant melanoma or pituitary adenoma.
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PMID:Neoplastic effects of oral contraceptives. 167 77

Concerns over the safety of oral contraceptives (OCs) have led to numerous empirical studies of the relationship of OC use to normal pregnancy outcomes, pituitary effects, cardiovascular accidents, and cancer. The article reviews some of the results of studies on the effects of OC use on ovarian, uterine, cervical, and breast cancer and on hepatic cancer and melanomas. Reference is made to direct study results rather than to reviews of studies, although it is noted that the critical reviews of Goldzieher and Realini reflect appropriate critiques of the validity of the methods employed in the analysis of cancers as well as cardiovascular risks. Concern is raised for meta-analysis of pooled data. In spite of the 30 years of research on OCs there is no definitive answer to the question of cause and effect. The epidemiological articles reviewed do not meet the standards of critical editorial review boards of experimental journals; confirmation of findings is also lacking. Studies suggesting increased risks as well as those showing positive benefits are questionable. The conclusion reached is that OCs protect against ovarian and uterine cancers and do not cause mammary, cervical, or liver cancer or melanoma. This conclusion is based on inconclusive data. The conclusion on hepatic cancer is that the 3 retrospective case control studies and anecdotal reports are flawed in design, and little confidence can be placed on such a limited number of cases. Malignant melanoma conclusions are that the data are inconsistent and hover around a risk of one for long-term OC-users. There is no increased risk related to OC-use. Ovarian cancer risk seems to be decreased in about 40% of OC-users. Endometrial cancer risk seems to be decreased, except for the sequential contraceptive Oracon which is associated with increased risk. Decreased risk is related to length of usage and continues after stoppage. Cervical carcinoma results appear to confirm the finding that prolonged OC use slightly increases the risk, but confounding factors may be present. Breast cancer shows no association with OC use, but inconsistent data among subgroups, particularly young women who used OCs before their first birth, some increased risks show.
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PMID:Oral contraceptives and cancer. 168 3

The beneficial effects of combined estrogen-progestin-containing oral contraceptives (OCs) include prevention of pregnancy (less than 1 failure out of 100 regular users); the prevention of ectopic pregnancy; the reduction of preeclampsia (2.4 times lower risk compared with barrier methods); and reduction of pelvic inflammation to about one-half. The effects on menstruation include the reduction of sideropenic anemia (by lowering the incidence and duration of menstruation, OCs reduce the loss of iron to 50% or to as much as 33%); dysmenorrhea by 40% (symptoms receded in 90% of users); and premenstrual syndrome by 30%. OCs exert a favorable effect on menstrual epilepsy; reduce sports-related accidents in the premenstrual and menstrual periods; and reduce intermenstrual bleeding. The protection from cancer includes the lowering of endometrial cancer risk (every 2 years of use reduces the risk by 38%, 12 years of use by 70%, and the beneficial effects last 3-15 years); reduction of the risk of the ovarian cancer (already 3-6 months of use reduces the risk by 30%, and more than 5 years by 50% in women under 50 years of age with a longterm effect of 10 years or more, which drops sharply in women over 60 who are mostly at risk). Among other beneficial effects, they reduce benign mastopathy by 50-75%; reduce the risk of follicular ovarian cysts to 50% and the risk of corpus luteal ovarian cysts to 1/5; and they lessen bone loss which favorably affects osteoporosis. Low-dose OCs minimize the well-known risks of thrombotic and cerebrovascular accidents, myocardial infarction, hypertension, altered carbohydrate metabolism, gallbladder diseases, and liver cancer. A new OC with 30 mcg of ethinyl estradiol was tested with daily doses of 150 mcg of desogestrel. The high density lipoprotein (HDL) either increased or did not change with desogestrel: the HDL2 subfraction that protects from atherosclerosis did not change, and probably the HDL3 raised the HDL level.
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PMID:[Favorable effects of oral estrogen-progestin contraception]. 181 41

The association between oral contraceptives (o.c.) and disease risk was reviewed on the basis of data from a network of a case-control studies conducted in northern Italy since the early 1980's on about 150 cases below age 55 with acute myocardial infarction, 150 with gallstone disease, 350 with uterine fibromyoma, 170 with endometrial cancer, 700 with benign or malignant ovarian tumours, 2000 with breast cancer, 360 with intraepithelial and 370 with invasive cervical cancer, 20 with liver cancer plus over 2000 control women admitted to hospital for acute, non hormone-related non neoplastic diseases. The relative risk (RR) of myocardial infarction was 2.1 (95% confidence interval from 0.7 to 7.1) among current o.c. users, but only 4% of women were current users. There was no association between gallstone disease, uterine fibromyoma and o.c. use. Significant protections were observed with reference to endometrial cancer and benign, borderline and malignant ovarian tumours, while the RR was above unity (RR = 1.9) for invasive cervical cancer, but not for intraepithelial cervical neoplasia. A significantly increased risk was observed for primary liver cancer, which is however extremely rare in young women. With reference to breast cancer, there was no consistent duration-risk relationship, and the RR was 0.8 for use for 5 or more years. Thus, these data provide reassuring information on the relationship between o.c. use and the risk of several important diseases in a Southern European population.
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PMID:[Risks and benefits of the contraceptive pill. A review of the results of an Italian study]. 184 65

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

Using data on potential years of life lost to ages 75 and 85, the potential effect of antiestrogens and estrogens on various competing causes of death is explored. Although for antiestrogens the beneficial effect sought is a reduction in breast cancer mortality, this could be largely eliminated by a small detrimental effect on cardiovascular disease mortality. Other competing causes of death, such as endometrial, ovarian, and liver cancer, and fractured neck of femur (as an indicator of osteoporosis), are of far less import. For estrogen use at the time of the menopause, no effect on mortality is sought. However, an adverse effect on breast cancer mortality would be of far greater significance than an effect on endometrial cancer. Indeed, the present endeavor to counter an adverse effect of estrogens on endometrial cancer by adding progestogens could be counterproductive. These competing causes of mortality have to be borne in mind in designing intervention trials.
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PMID:Risk/benefit considerations of antiestrogen/estrogen therapy in healthy postmenopausal women. 200 29

Mortality is the greatest concern in assessing risks of modern reversible contraception. The problems identified with older oral contraceptives (OCs) have decreased with the lower doses in current OCs. These problems include cardiovascular and thrombotic effects, changes in lipid metabolism, breast cancer, liver cancer, increased risk of chlamydia cervicitis, no protection against sexually transmitted diseases (STDs) and HIV, and interferes with breast feeding. On the other hand, OCs protect against anemia, menstrual disorders, ectopic pregnancy, acute pelvic inflammatory disease (PID), and ovarian and endometrial cancer. Since the contraceptive implant, Norplant, has no estrogens, it does not have the cardiovascular risks associated with OCs. Possible risks from Norplant use include changes in carbohydrate, liver, and lipid metabolism but they tend to be clinically insignificant and no protection against STDs/HIV. Menstruation disorders are the major side effect. Apparent benefits of Norplant are protection against anemia and ectopic pregnancy and no effect on lactation. The injectable contraceptive, Depo-Provera, causes menstrual changes, may slightly increase the risk of breast cancer, may decrease bone density, and does not protect against STDs/HIV. It protects against endometrial cancer. It has no effect on metabolism. Risks associated with the IUD include PID, perforation, anemia, increased menstrual bleeding, and pregnancy. IUDs do not affect the quantity of composition of breast milk. They are best suited for women in a mutually monogamous, long-term relationship. Barrier methods provide some degree of protection against STDs/HIV and PID. Condoms provide the most protection. They do not affect lactation. Their major complications are contraceptive failure and risks associated with pregnancy. For all women, especially those in high risk categories, one must balance the risks of modern contraceptive use with the risks of childbearing and with their benefits.
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PMID:The safety of modern contraceptives. 784 6


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