Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anastrozole, a nonsteroidal selective aromatase inhibitor, has recently been approved in the US and several other countries for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. In the Arimidex, Tamoxifen alone or in Combination (ATAC) trial, anastrazole 1mg was significantly more effective than tamoxifen 20mg or combined treatment (17 and 19% relative risk reduction) for disease-free survival in postmenopausal women with early breast cancer. black triangle Anastrazole was also significantly more effective than tamoxifen for time to tumour recurrence and the odds of a primary contralateral tumour as a first event. During the first 2 years of treatment with anastrozole, tamoxifen or the combination, patient quality of life was similar in all treatment groups. Compared with tamoxifen, anastrozole was associated with a significantly lower incidence of vaginal bleeding, vaginal discharge, hot flushes, endometrial cancer, ischaemic cerebrovascular events, venous thromboembolic events and deep vein thrombosis including pulmonary embolism; tamoxifen was associated with a lower incidence of musculoskeletal disorders and fracture.
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PMID:Anastrozole: in early breast cancer. 1242 Nov 8

Cardiovascular disease (CVD) is the leading cause of death in the developed world for both men and women. Women experience significant alterations in lipid profiles during the years following menopause, including a reduction in plasma high-density lipoprotein cholesterol and an elevation of plasma low-density lipoprotein cholesterol, and are at an increased risk of CVD. These changes are due in part to the reduction in estrogen production following the onset of the menopause. Therefore, agents that have anti-estrogenic effects, such as most endocrine therapies for breast cancer, may increase the risk of CVD. Tamoxifen, historically the standard endocrine therapy, has an overall beneficial effect on lipid profiles. However, long-term data from clinical trials have failed to demonstrate a cardioprotective effect and patients treated with tamoxifen did not experience fewer cardiovascular events compared with those receiving placebo. Indeed, a number of studies have shown that tamoxifen may have a detrimental effect, with a significantly increased risk of venous thromboembolic events, pulmonary embolism and stroke. The third-generation aromatase inhibitors (AIs) have demonstrated an improvement in efficacy and tolerability over previous treatments. Since they have a different mechanism of action to tamoxifen, they are not anticipated to exert the same impact on lipid profiles. Clinical trials with anastrozole demonstrated no clinically relevant impact on lipid profiles in postmenopausal patients with advanced breast cancer. However, as lipid profiles are surrogate endpoints, the most appropriate endpoint is the incidence of cardiovascular events in long-term studies. This is of particular relevance in the treatment of early breast cancer, where endocrine agents may be used in the adjuvant setting for periods of 5 years or more. Long-term adjuvant anastrozole treatment resulted in significantly fewer thromboembolic and cerebrovascular events and a similar incidence of ischemic cardiovascular events compared with tamoxifen. The effects of the other AIs on lipid levels are variable, and any correlation with cardiovascular events is currently unknown.
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PMID:Comparative assessment of lipid effects of endocrine therapy for breast cancer: implications for cardiovascular disease prevention in postmenopausal women. 1623 14

Toremifene has been in clinical use for 8 years for the treatment of advanced hormone-sensitive breast cancer and the adjuvant treatment of early breast cancer. More than 350,000 patient treatment years have accumulated, sufficient to allow evaluation of its longer-term safety profile in comparison with tamoxifen and, where possible, with raloxifene and aromatase inhibitors. We reviewed all preclinical and clinical safety data from 1978 to 2004 and comparative clinical safety data between October 1995 and the end of 2004. Secondary endometrial cancer incidence was lower with toremifene than with tamoxifen and was similar to that with raloxifene. It is speculated that toremifene may unmask existing endometrial tumors rather than induce new events. The risk of stroke, pulmonary embolism, and cataract may be lower with toremifene than with tamoxifen and the risk of pulmonary embolism and deep vein thrombosis lower than with raloxifene. Beneficial estrogen agonistic effects were equivalent to those of tamoxifen regarding bone mineral density and superior regarding lipid profiles.
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PMID:Toremifene: an evaluation of its safety profile. 1628 4

In 1998, the concept of breast cancer prevention became a reality with the approval of tamoxifen to reduce the risk of developing breast cancer in women at increased risk for the disease. This approval was based on decades of research on selective estrogen receptor modulators providing an understanding of the role of the estrogen receptor in breast cell growth, and an appreciation of the carcinogenic process. Although results from the Breast Cancer Prevention Trial demonstrated a 49% reduction in breast cancer in women at increased risk, there were associated toxicities related to the estrogenic effects of tamoxifen; that is, deep vein thrombosis, pulmonary embolism, and endometrial cancer. In an effort to improve its benefit-risk profile, tamoxifen is now being compared with raloxifene, a selective estrogen receptor modulator approved for the treatment and prevention of osteoporosis. This equivalency prevention Study of Tamoxifen and Raloxifene completed accrual of 19 747 high-risk postmenopausal women in November 2004. Meanwhile, another class of estrogen-directed drugs, the aromatase inhibitors, have shown efficacy in breast cancer adjuvant trials, spawning a number of prevention trials that have recently been initiated. As with breast cancer the hormonal contribution to prostate carcinogenesis was the basis for the Prostate Cancer Prevention Trial which showed that finasteride, an androgen antagonist, reduces the incidence of prostate cancer compared to placebo.
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PMID:Hormonal interventions to prevent hormonal cancers: breast and prostate cancers. 1741 94

In patients with early-stage breast cancer, all recurrences are associated with an increased risk of mortality, especially distant metastases. Adjuvant tamoxifen therapy for 5 years is effective in postmenopausal patients for the prevention of disease recurrence but is associated with increased risk of rare, potentially fatal adverse events such as endometrial cancer, stroke, and pulmonary embolism. Recently, randomized clinical trials have shown aromatase inhibitor therapy to be superior to tamoxifen therapy for the prevention of disease recurrence. Switching to an aromatase inhibitor after 2-3 years of tamoxifen treatment has been shown to provide superior disease-free survival compared with completing 5 years of tamoxifen. Among approved aromatase inhibitors (letrozole, anastrozole, and exemestane), letrozole is the only one approved as extended adjuvant therapy after completing 5 years of tamoxifen. These results suggest that 10 years of adjuvant endocrine therapy is superior to 5 years of tamoxifen alone.
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PMID:Adjuvant and extended adjuvant use of aromatase inhibitors: reducing the risk of recurrence and distant metastasis. 1806 55

Endocrine therapy has become a key part in the adjuvant treatment of hormone responsive breast cancer. The positive effect on relapse risk reduction is well defined, but therapy is not free from bothersome side effects for which estrogen deprivation accounts to a great extent. Since endocrine therapy is usually prescribed for 5 years or longer to optimally display its protective effect, and because physical strain is missing, good tolerability and safety properties are important, particularly in low-risk patients. While tamoxifen has been the standard adjuvant endocrine treatment with well documented efficiency, it is increasingly replaced by third generation aromatase inhibitors due to their better effectiveness and tolerability. Because tamoxifen holds a risk for life-threatening adverse events such as endometrial cancer, pulmonary embolism, and stroke, its recommended duration of therapy is limited to 5 years, also because extension beyond that time did not produce a measurable advantage. While some side effects are present both with tamoxifen and aromatase inhibitors, differences in side effect profiles are well established. Although side effects of aromatase inhibitor-related therapy usually are mild and common to symptoms of menopause, misconception of the symptoms and their mechanism of action, as well as lack of knowledge about how to handle them, can easily lead to dangerous discontinuation of therapy.
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PMID:Is Endocrine Therapy Really Pleasant? Considerations about the Long-Term Use of Antihormonal Therapy and Its Benefit/Side Effect Ratio. 2116 May 41

Decreased testosterone levels in men are often a normal sign of aging. Testosterone replacement therapy (TRT) is a well-established option for those with symptomatic hypogonadism related to low testosterone levels. Conversely, designer herbal supplements in the context of testosterone supplementation are poorly studied, yet remain popular among aging men who seek the well-known, often enhancing, effects of testosterone that involve muscle mass and sexual function/drive. In 2014, the Food and Drug Administration (FDA) issued a warning about the significant risk of venous clots secondary to testosterone product use. Testosterone-induced polycythemia is one of the proposed mechanisms for this increased clotting propensity. Increased thromboxane A2 receptor density on platelets and increased platelet aggregation have also been linked to testosterone treatment in men. Fenugreek extract is a common active ingredient in commercially available herbal supplements that are often marketed as testosterone enhancers. It is thought that certain fenugreek compounds inhibit aromatase and 5-alpha-reductase activity, leading to diminished testosterone breakdown. However, the efficacy and safety profile of this agent in its use for boosting testosterone levels are unclear. In this case report, we present a patient with new-onset, bilateral pulmonary embolism possibly associated with the daily use of fenugreek-containing testosterone supplements.
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PMID:Pulmonary Embolism Secondary to Testosterone-Enhancing Herbal Supplement Use. 2901 42