Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003862 (arthralgia)
 7,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adjuvant endocrine therapy plays an important role in the management of hormone-receptor-positive early breast cancer, and has increased life expectancy for millions of women. Many patients receive adjuvant treatment for at least 5 years following tumor resection, hence good long-term safety is important for endocrine agents to gain widespread acceptance. Tamoxifen has been used as adjuvant therapy for early breast cancer for many years, and safety data have been well documented, but a poor risk:benefit profile limits treatment duration to 5 years. Increased efficacy over tamoxifen and good tolerability have recently made the third-generation aromatase inhibitors (AIs) the first-choice agents for adjuvant endocrine therapy; however, it is currently not known whether AI therapy, like tamoxifen, will be limited to 5 years. Many side effects of endocrine therapy, such as hot flushes and mood disturbances, are related to estrogen deprivation and are common to tamoxifen and AIs, reflecting the mechanism of action of these drugs. In addition, tamoxifen has estrogenic effects that are beneficial in some tissues: tamoxifen lowers serum cholesterol levels and protects against bone loss and cardiovascular disease, but is also associated with potentially life-threatening side effects, such as endometrial cancer and thromboembolic disease. As AIs lack estrogenic activity, they are not associated with these serious adverse events. Clinical trials comparing AIs with tamoxifen in the adjuvant setting have shown that AIs are well tolerated and are associated with a lower incidence of gynecological symptoms and hot flushes than tamoxifen. However, AIs are associated with musculoskeletal side effects, such as arthralgia, myalgia and bone loss, but these events are preventable or manageable. The effects of AIs on lipid metabolism and the cardiovascular system are still debatable, but placebo-controlled trials provide no evidence to suggest that AIs adversely affect these systems. Furthermore, the AIs allow women to maintain a good quality of life, comparable with women receiving tamoxifen or placebo, and are a cost-effective therapeutic option. Ongoing trials will provide more information regarding the long-term effects of AI therapy and will provide comparative data on the efficacy and safety of the different AIs, thereby helping to determine the optimal treatment strategy for these highly effective and well-tolerated drugs.
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PMID:Safety profiles of tamoxifen and the aromatase inhibitors in adjuvant therapy of hormone-responsive early breast cancer. 1789 Feb 11

It is well documented that the aromatase inhibitors (AIs) are superior to tamoxifen as adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive breast cancer. However, compared with tamoxifen, an elevated incidence of arthralgia has been observed during AI treatment. Concerns have been raised that AI-induced arthralgia may dissuade patients from completing their full AI treatment course, and may also deter physicians from prescribing an AI if they feel that patients may be at risk of permanent joint damage. Patient education about the possibility of experiencing arthralgia, and effective management of symptoms if they appear, are important in helping patients adhere to AI treatment, and consequently improving breast cancer outcomes. In this paper, we discuss the potential mechanisms behind AI-induced arthralgia, review the frequency with which arthralgia occurs, and propose for the first time an algorithm specifically for the treatment of AI-induced arthralgia. As with joint pain in non-breast cancer patients, a sequential approach to disease management is recommended, involving modifying the patient's lifestyle in addition to taking a stratified approach to pharmacological intervention with analgesia and anti-inflammatory medication. Knowing that joint symptoms can be managed in most patients may encourage patient-physician communication and treatment compliance.
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PMID:Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations. 1808 28

For the upfront adjuvant therapy of postmenopausal estrogen receptor-positive breast cancer, the third-generation aromatase inhibitors (AIS) have shown a more favourable overall risk-benefit profile than has tamoxifen. Benefits of the ais include less frequent gynecologic, cerebrovascular, and thromboembolic adverse events; greater disease-free survival; and lower tumour recurrence. Although approximately 25% of postmenopausal women with early breast cancer report experiencing symptoms of arthralgia with ai therapy, 68-month data from the Arimidex, Tamoxifen, Alone or in Combination trial showed that, compared with tamoxifen, anastrozole treatment was associated with only a modest increase in the incidence of joint symptoms. The events, which were mostly mild-to-moderate in intensity, led to treatment withdrawal in 2% of patients on anastrozole as compared with 1% in the tamoxifen arm. The symptoms and changes correlate with clinical, biochemical, and radiologic findings in symptomatic women. To determine appropriate intervention, it is therefore essential to perform a comprehensive evaluation of musculoskeletal complaints to distinguish natural menopause-related degenerative disease from AI-related effects. The present review explores the advantages of differential diagnosis with an emphasis on history and physical and musculoskeletal examination; laboratory investigations are used to corroborate or rule out clinical impressions. The transient symptoms associated with the ais are manageable with an appropriate combination of lifestyle changes, including exercise and joint protection in conjunction with pharmacologic approaches.
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PMID:Management of arthralgias associated with aromatase inhibitor therapy. 1808 4

Autoantibodies and lupus-like syndromes can develop following the use of certain medications; however, although many patients develop autoantibodies, only a minority develop clinical features. Although these autoantibodies primarily consist of antinuclear and antihistone antibodies, additional types of antibody, such as antineutrophil cytoplasmic antibodies and anti-double-stranded DNA antibodies, have been reported in association with minocycline and tumor necrosis factor inhibitor therapy. Clinical features of drug-related lupus usually consist of constitutional symptoms, arthralgias, arthritis, myalgias and serositis, although cutaneous manifestations have been reported in association with the use of tumor necrosis factor inhibitors. Typically, clinical features resolve with discontinuation of the medication, although antibodies can persist for months or years. Arthralgias and inflammatory arthritis have also been reported in association with the use of aromatase inhibitors and other biologic agents such as interleukins and interferons.
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PMID:Drug insight: autoimmune effects of medications-what's new? 1820 8

Third-generation aromatase inhibitors (AIs) are replacing tamoxifen as adjuvant therapy in postmenopausal women with hormone-sensitive breast cancer due to their superiority shown in several recent head-to-head trials. Healthy postmenopausal women normally experience age-related side effects, and in postmenopausal women with breast cancer, these symptoms may be exacerbated by adjuvant endocrine therapy. This review evaluates the current literature regarding bone health, lipid metabolism, cardiovascular disease, gynecologic health, and cognition in postmenopausal women receiving adjuvant AI therapy. The AIs -- anastrozole, exemestane, and letrozole -- are generally well tolerated: most adverse events are mild to moderate and common to menopause. Common short-term AI-associated toxicities are hot flushes, musculoskeletal complaints/arthralgia, and bone loss, all of which can be effectively managed. AIs may lack the cardioprotective and lipid-lowering effects of tamoxifen but, in contrast to tamoxifen, do not increase the risk of serious life-threatening thromboembolic or cerebrovascular events or endometrial cancer. Every patient should be individually assessed with respect to therapy risks and benefits. Lifestyle, comorbidities, and concomitant medications must be considered, and the importance of compliance to adjuvant therapy should be discussed before selecting a treatment regimen. The superior efficacy of adjuvant AI therapy will in most cases outweigh the risk of bothersome side effects that can be prevented or easily managed.
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PMID:Menopausal symptoms and adjuvant therapy-associated adverse events. 1831 Feb 77

Recently aromatase inhibitors have become a standard care as an adjuvant treatment for many postmenopausal patients with hormone receptor positive early breast cancer. Adjuvant letrozole was made available either immediately postoperative, after 2-3 years of tamoxifen, or as an extended treatment after 5 years of tamoxifen. Between October 2003 and October 2005, we analyzed the subjective tolerance in 185 postoperative early breast cancer patients receiving letrozole outside of a clinical trial. The most prominent toxicity was musculoskeletal pain. In addition hot flushes, increased fatigue, nausea, vomiting, anorexia, mood disturbances, vaginal dryness, hair loss and rash were also recorded. In contrast to the prospective randomized clinical trials, a high drop-out rate of 20% was documented, mainly due to aromatase inhibitor-associated arthralgia syndrome interfering significantly with the daily life of our patients. Although adjuvant aromatase inhibitors have proven to be generally superior to tamoxifen in the adjuvant setting, it is important to focus attention on the tolerance during the adjuvant therapy and to balance this against the potential benefit in individual patients. Alternative options including switching to tamoxifen remain available.
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PMID:Tolerance of adjuvant letrozole outside of clinical trials. 1845 95

Surveillance following curative therapy for localised breast cancer has two major aims: 1) diagnosis of recurrence or a second tumor: regular interviews and physical examinations with a frequency adapted to each case, and yearly mammography (+/- ultrasonography), are the only recommended procedure. Additional screening is not indicated in asymptomatic patient. 2) Screening for complications and side effects due to treatment: tamoxifen treatment should be stopped one week prior to any surgery or long trip to avoid thromboembolic events, and any metrorrhagia should be investigated due to the risk for endometrial cancer. Osteoporosis and arthralgia are frequently observed with aromatase inhibitors.
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PMID:[Surveillance following curative therapy for breast cancer]. 1861 8

Following promising data for metastatic breast cancer in terms of efficacy and safety profile, third-generation aromatase inhibitors (AI), anastrozole, letrozole, and exemestane, underwent a full development in early setting. If recent results consistently show the superiority of these agents over tamoxifen, the therapeutic strategies of AIs in adjuvant setting are still debated. Beyond the choice of clinical strategy, the long duration of exposure to AI in adjuvant setting required a full determination of the long-term toxicity profile of these agents. While all three AIs have either favorable (decreased incidence of hot flashes, gynecologic and thromboembolic side-effects) or unfavorable (skeletal complications, arthralgia, musculoskeletal pain, sexual dysfunction) class adverse events, some variability between AIs has been reported in side-effects as well as gastrointestinal, urogenital, neurologic, and visual disturbances, confirming the lack of interchangeability between the three AIs. The overall therapeutic index of AIs appears today superior to that of tamoxifen with proven improved efficacy and better toxicity profile. This review will explore the results from the available adjuvant AIs trials with a particular emphasis on safety profiles, quality of life, and therapeutic index, helping to define the present role of AIs in the adjuvant management of postmenopausal patients with breast cancer.
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PMID:Long-term safety of aromatase inhibitors in the treatment of breast cancer. 1872 7

Aromatase inhibitors (AIs) enjoy increasing use in breast cancer adjuvant therapy. But the joint pain associated with AIs significantly reduces patient adherence despite the clear survival benefits of this class of drugs. Two clues point to a novel hypothesis for this unexplained symptom. First, realizing that joint pain is associated with virtually all estrogen-depleting breast cancer treatments suggests that the cause is broader than this particular class of drugs. Second, the strongly circadian nature of these symptoms suggests circadian hormone involvement. This puts new light on some existing research findings: that estrogen depletion can increase pineal melatonin, that the ability of light to suppress pineal melatonin is more variable than once thought, and that an altered melatonin cycle is associated with rheumatoid arthritis patients, where identical circadian symptoms present. It is hypothesized that when AIs decrease estrogen levels, light-induced melatonin suppression (LIMS) loses efficacy, leading to an abnormal melatonin cycle as seen in rheumatoid arthritis patients, producing (via mechanisms not yet understood) the symptoms of morning stiffness. Not all frequencies of retinal light are equally effective at suppressing pineal melatonin; most artificial lighting has less relevant spectral density than sunlight. This hypothesis predicts that some patients can suppress the circadian joint pain associated with aromatase inhibitors merely by getting sufficient hours of daily retinal sunlight. A single patient history is discussed, in which a series of treatments had no effect on AI joint pain, while extended exposure to sunlight produced a definitive elimination of symptoms the next morning. To conclusively demonstrate the role of melatonin, light-emitting diodes of an appropriate frequency were mounted on a cap for the patient to wear. If worn first thing in the morning, the cap sharply curtailed the duration of morning stiffness. If worn for a sufficient number of hours during the day, the cap suppressed symptoms the next morning, just as sunlight did. Because of evidence for melatonin's oncostatic properties, this hypothesis potentially has implications beyond decreasing the number of patients that discontinue AIs. It may be that some portion of the survival benefit of AIs is due to their indirect effect on melatonin, not just their direct effect on estrogen.
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PMID:Aromatase inhibitor-induced joint pain: melatonin's role. 1878 56

The use of aromatase inhibitors (AIs) as adjuvant endocrine therapy for hormone-sensitive breast cancer is increasing, as these drugs are more effective than tamoxifen alone in improving disease-free survival in breast cancer patients-whether used in lieu of tamoxifen as upfront therapy or after tamoxifen treatment periods of 2 years or longer. AIs differ from tamoxifen in their mechanism of action, effectively suppressing estrogen levels in postmenopausal women to near-undetectable levels. AI-associated adverse events largely mimic menopausal symptoms, including hot flashes, losses in bone mineral density, gynecologic symptoms, and arthralgias. The AIs lack the infrequent but potentially serious adverse events associated with tamoxifen (eg, endometrial cancer, thromboembolic events, and stroke). Large randomized studies of AIs in the adjuvant setting have not demonstrated an adverse effect on lipids and cardiovascular health, but postmenopausal women receiving AIs are at risk for age-related changes in lipid parameters and an increased risk for cardiovascular events. To optimize the overall benefits of adjuvant endocrine therapy with an AI, patients should be monitored for bone loss and cardiovascular risk factors, and symptoms such as joint pain and vaginal dryness should be anticipated and managed proactively.
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PMID:Safety of adjuvant endocrine therapy in postmenopausal women with breast cancer. 1906 May 94


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