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

Tamoxifen (TAM) is a selective estrogen-receptor modulator that is widely used in the prevention and treatment of estrogen-receptor-positive breast cancer. Its use has significantly contributed to a decline in breast cancer mortality, since breast cancer patients treated with TAM for 5 years exhibit a 30-50% reduction in both the rate of disease recurrence after 10 years of patient follow-up and in the occurrence of contralateral breast cancer. However, in patients treated with TAM, there is substantial interindividual variability in the development of resistance to TAM therapy and in the incidence of TAM-induced adverse events, including deep-vein thrombosis, hot flashes, and the development of endometrial cancer. Aromatase inhibitors (AIs) have emerged as a viable alternative to TAM, working by inhibiting aromatase activity and blocking estrone/estrodiol biosynthesis in postmenopausal women. The current third-generation AIs, anastrozole, exemestane, and letrozole, were used initially for the treatment of metastatic breast cancer, demonstrating similar or greater benefit but less toxicity, compared with TAM, and are now being employed as adjuvant treatment for early breast cancer in postmenopausal women. This article will focus on the UDP-glucuronosyltransferases, a family of metabolizing enzymes that play an important role in the deactivation and clearance of TAM, anastrazole, and exemestane, and how interindividual differences in these enzymes may play a role in patient response to these agents.
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PMID:Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen and aromatase inhibitors. 1982 43

Tamoxifen is an orally active selective estrogen receptor modulator that is used in the treatment of breast cancer and is currently the world's largest selling drug for that purpose. However, it has some side effects including hot flashes, menstrual irregularity, vaginal discharges, uterine bleeding, uterine endometrial cancer, hypercoagulability, steatosis hepatis, risk of trombembolism. Long-term data from clinical trials have failed to demonstrate a cardioprotective effect and beneficial effects on serum lipid profiles. Arrhythmia secondary to tamoxifen is very rare.
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PMID:Tamoxifen and arrhythmia. 1791 98

Matters of sexuality and intimacy greatly impact quality of life of patients with gynecologic cancers. Vast amount of evidence exists showing that cancer dramatically impacts woman's sexuality, sexual functioning, intimate relationships and sense of self. Sexual functioning can be affected by illness, pain, anxiety, anger, stressful circumstances and medications. There is a growing acknowledgement that these needs are not being appropriately addressed by providers. With improvements in early detection, surgery and adjuvant therapy for gynecologic cancer, long term survival and cure are becoming possible. Quality of life is thus becoming a major issue for patients. Patients suffer from hot flashes, difficulty sleeping, loss of libido and intimacy, all resulting in significant morbidity and loss of quality of life. Using hormone replacement therapy in gynecologic cancer survivors is a topic a great debate. While limited studies are available to date, retrospective cohort reviews show no reported differences in overall or disease-free survival in patients using hormone replacements vs. controls in patients with ovarian cancer, endometrial cancer, cervical, vaginal or vulva cancer. Since safety of using HRT remains controversial and prospective studies are lacking, providers need to be able to provide alternatives to HRT. Centrally acting agents such as antiseizure agent gabapentin and selective serotonine re-uptake inhibitors, such as venlafaxine and fluoxitine have been demonstrated to show effectiveness in treating vasomotor symptoms and are easily tolerated. To address cardiovascular and osteoporosis risks of post-menopausal status, exercise, healthy diet, bisphosphonates, raloxifen and statins have been found to be effective. Psychotherapy plays an essential part in management of these issues. Review of the literature reveals recent trends among health psychologists to utilize psychoeducational interventions that include combined elements of cognitive and behavioral therapy with education and mindfulness training. Intervention studies have found positive effects from this approach, particularly within the areas of arousal, orgasm, satisfaction, overall well-being, and decreased depression. Many of patients' issues are easy to address with either hormonal, non-hormonal or psychotherapy modifications. The essential part of success is the providers appreciation of this serous problem and willingness and comfort in addressing it.
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PMID:Sexuality and intimacy after gynecological cancer. 2030 22

Exemestane is an irreversible inhibitor of the aromatase enzyme, which is a key component in the production of estrogen. The majority of breast cancers are sensitive to the proliferative effects of estrogen. Exemestane is approved for the adjuvant treatment of postmenopausal women with breast cancer after 2 to 3 years of tamoxifen therapy, based on a 32% improvement in disease-free survival compared with 5 years of tamoxifen alone (P < 0.001). Exemestane has also shown clinical benefits as an upfront therapy. The safety profile of exemestane shares some side effects with tamoxifen (hot flashes and arthralgia), but is not associated with an increased risk of endometrial cancer or thromboembolic events. This review will discuss in detail the efficacy and safety of exemestane in early breast cancer.
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PMID:Exemestane in the adjuvant treatment of breast cancer in postmenopausal women. 2208 74

Uterine leiomyomata are benign, monoclonal tumors arising from smooth muscle cells, which belong to one of the most common pathologies of the female genital system. Current pharmacotherapies (oral contraceptives, progestins, GnRH analogs) are ineffective or of limited use for long-term treatment. Although there is still much debate regarding their etiology it is very likely that progesterone and progesterone receptor play a key role in their development. Profound importance of progesterone in the female reproductive system has led to discovery of synthetic progesterone receptor ligands, which can poses the activity ranging from pure agonist activity trough mixed agonist/antagonist activity to pure antagonist activity Development of selective progesterone receptor modulators (SPRM) has created new therapeutic options and has great potential in a number of gynecologic indications. So far, ulipristal acetate has been approved for emergency contraception, mifepristone as a progesterone receptor antagonist because of the unique property of this compound for termination of pregnancy Recently the European Commission has authorized ulipristal acetate for the pre-operative treatment of uterine fibroids. Superior efficacy of ulipristal acetate versus placebo, to reduce excessive uterine bleeding and to reduce total fibroid volume prior to surgery was demonstrated. Moreover non-inferior efficacy of ulipristal acetate versus Gonadotropin Releasing Hormone (GnRH)-agonist to reduce excessive uterine bleeding prior to surgery of uterine fibroids has been documented. Ulipristal acetate is also characterized by a superior side-effect profile in comparison to leuprolide acetate in terms of serum estradiol levels and the proportion of patients with moderate-to-severe hot flashes during treatment. Regarding safety profile, except elevation of liver enzymes after telapristone and onapristone treatment, to date no serious untoward effects of other SPRM have been reported. The issue of endometrial effects of these compounds remains to be resolved, although observation that intrinsic agonist activity of SPRM prevents endometrial proliferation may suggest future use of these agents in prevention of endometrial hyperplasia. Other promising applications, including endometriosis, endometrial cancer Cushing's disease, Alzheimer disease or long-term contraception, are currently in development.
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PMID:[Applicability of selective progesterone receptor modulators in the treatment of uterine leiomyomata and their future role in the field of gynecology]. 2419 19

The discovery of the first nonsteroidal antiestrogen ethamoxytriphetol (MER25) in 1958, opened the door to a wide range of clinical applications. However, the finding that ethamoxytriphetol was a "morning after" pill in laboratory animals, energized the pharmaceutical industry to discover more potent derivatives. In the wake of the enormous impact of the introduction of the oral contraceptive worldwide, contraceptive research was a central focus in the early 1960's. Numerous compounds were discovered e.g., clomiphene, nafoxidine, and tamoxifen, but the fact that clinical studies showed no contraceptive actions, but, in fact, induced ovulation, dampened enthusiasm for clinical development. Only clomiphene moved forward to pioneer an application to induce ovulation in subfertile women. The fact that all the compounds were antiestrogenic made an application in patients to treat estrogen responsive breast cancer, an obvious choice. However, toxicities and poor projected commercial returns severely retarded clinical development for two decades. In the 1970's a paradigm shift in the laboratory to advocate long term adjuvant tamoxifen treatment for early (non-metastatic) breast cancer changed medical care and dramatically increased survivorship. Tamoxifen pioneered that paradigm shift but it became the medicine of choice in a second paradigm shift for preventing breast cancer during the 1980's and 1990's. This was not surprising as it was the only medicine available and there was laboratory and clinical evidence for the eventual success of this application. Tamoxifen is the first medicine to be approved by the Food and Drug Administration (FDA) to reduce the risk of breast cancer in women at high risk. But it was the re-evaluation of the toxicology of tamoxifen in the 1980's and the finding that there was both carcinogenic potential and a significant, but small, risk of endometrial cancer in postmenopausal women that led to a third paradigm shift to identify applications for selective estrogen receptor (ER) modulation. This idea was to establish a new group of medicines now called selective ER modulators (SERMs). Today there are 5 SERMs FDA approved (one other in Europe) for applications ranging from the reduction of breast cancer risk and osteoporosis to the reduction of menopausal hot flashes and improvements in dyspareunia and vaginal lubrication. This article charts the origins of the current path for progress in women's health with SERMs.
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PMID:The evolution of nonsteroidal antiestrogens to become selective estrogen receptor modulators. 2494 34

Adjuvant endocrine therapy (ET) reduces the odds of distant recurrence and mortality by nearly one-half in women with hormone receptor (HR) positive early stage breast cancer. While the risk of recurrence is lower for HR positive than negative patients during the first 5-7 years, HR positive patients suffer ongoing recurrences between 0.5 and 2% year over subsequent years. Extended adjuvant ET further reduces recurrence during this late phase of follow-up. ET is associated with post-menopausal side effects (hot flashes, sexual dysfunction, mood changes, and weight gain), and occasional major toxicities (thrombosis and endometrial cancer with tamoxifen; bone mineral loss and possibly heart disease with AIs) persist throughout therapy. Accurate and reliable estimates of the risk of recurrence after five years of ET for women with prior HR positive breast cancer would permit appropriate extended ET decisions. The risk of long-term relapse is related to lymph node status and size of tumor, but these are relatively crude. Several groups have investigated whether multi-parameter tumor biomarker tests might identify those patients whose risk of recurrence is so low that extended ET is not justified. These assays include IHC4, the 21-gene "OncotypeDX", the 12-gene "Endopredict," the PAM50, and the 2-gene "Breast Cancer Index (BCI)" assays. The clinical validity of all these tests for this use context have been established, with at least one paper for each that shows a statistically significant difference in risk of distant recurrence during the 5-10 years after the initial five years of adjuvant endocrine therapy. However, the stakes are high, and although each of these represents a "prospective retrospective" study, they require further validation in subsequent datasets before they should be considered to have "clinical utility" and are used to withhold potentially life-saving treatment. Perhaps more importantly, the clinical breast cancer community, and especially the patient, need to determine how low the risk of late recurrence needs to be to forego the toxicities and side effects of extended adjuvant ET.
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PMID:Clinical utility of genetic signatures in selecting adjuvant treatment: Risk stratification for early vs. late recurrences. 2623 37

The results of large clinical trials have led physicians and patients to question the safety of hormone therapy for menopause. In the past, physicians prescribed hormone therapy to improve overall health and prevent cardiac disease, as well as for symptoms of menopause. Combined estrogen/progestogen therapy, but not estrogen alone, increases the risk of breast cancer when used for more than three to five years. Therefore, in women with a uterus, it is recommended that physicians prescribe combination therapy only to treat menopausal symptoms such as vasomotor symptoms (hot flashes) and vaginal atrophy, using the smallest effective dosage for the shortest possible duration. Although estrogen is the most effective treatment for hot flashes, nonhormonal alternatives such as low-dose paroxetine, venlafaxine, and gabapentin are effective alternatives. Women with a uterus who are using estrogen should also take a progestogen to reduce the risk of endometrial cancer. Women who cannot tolerate adverse effects of progestogens may benefit from a combined formulation of estrogen and the selective estrogen receptor modulator bazedoxifene. There is no highquality, consistent evidence that yoga, paced respiration, acupuncture, exercise, stress reduction, relaxation therapy, and alternative therapies such as black cohosh, botanical products, omega-3 fatty acid supplements, and dietary Chinese herbs benefit patients more than placebo. One systematic review suggests modest improvement in hot flashes and vaginal dryness with soy products, and small studies suggest that clinical hypnosis significantly reduces hot flashes. Patients with genitourinary syndrome of menopause may benefit from vaginal estrogen, nonhormonal vaginal moisturizers, or ospemifene (the only nonhormonal treatment approved by the U.S. Food and Drug Administration for dyspareunia due to menopausal atrophy). The decision to use hormone therapy depends on clinical presentation, a thorough evaluation of the risks and benefits, and an informed discussion with the patient.
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PMID:Hormone Therapy and Other Treatments for Symptoms of Menopause. 2792 71


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