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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer is a leading cause of cancer-related mortality among postmenopausal women in the US, and the economic burden of breast cancer care comprises a large percentage of the healthcare budget. Hormonal therapies have a proven place in the management of advanced breast cancer. This type of therapy is more likely to be used in older, compared with younger, women, because tumours in older women are more likely to express estrogen and progesterone receptors. While it is difficult to measure the costs of cancer care because of variation in extent and duration of treatment, treatment-related costs including costs of hormonal agents used for advanced disease account for a relatively small component of the overall costs. Newer hormonal regimens such as the new third generation nonsteroidal (letrozole, anastrozole) and steroidal (exemestane) aromatase inhibitors have shown improved clinical efficacy compared with standard regimens such as megestrol and tamoxifen in the metastatic setting in terms of objective responses or time to tumour progression. In addition the newer agents have improved toxicity profiles. Cost analyses of the newer aromatase inhibitors (anastrozole and letrozole), compared with megestrol, show an optimistic outlook for these agents. Additional work needs to be done looking at a comparison of the efficacy and costs of the aromatase inhibitors relative to the currently recommended hormonal treatments used for women with metastatic breast cancer.
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PMID:Efficacy and economics of hormonal therapies for advanced breast cancer. 1214 51

In the last 40 years tamoxifen and progestogens constituted the basis of hormonal therapy. Introduction of the third generation, selective, anti-aromatase agents added effective drugs of good tolerability to the anti-cancer armamentarium. Exemestane, an oral steroidal-type aromatase inhibitor - which irreversibly blocks aromatase - is very effective in the treatment of metastatic breast cancer. As a second line therapy, exemestane is more effective and causes less side effects than megestrol-acetate. Its administration as first line therapy gave promising results. The role of exemestane in adjuvant treatment has not yet been soundly established but trials are ongoing. It may be effective as neoadjuvant treatment in selected groups of patients. Future studies will clarify exemestane's role in chemoprevention and in the treatment of post-menopausal women administered together with cytostatic agents.
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PMID:The role of aromasin in the hormonal therapy of breast cancer. 1217 71

Third-generation aromatase inhibitors and inactivators have earned their place in the treatment of metastatic breast cancer. The third-generation aromatase inactivator exemestane was found to be superior to megestrol acetate as second-line endocrine therapy in postmenopausal women, with respect to time to progression as well as overall survival, and the results from an ongoing study comparing exemestane with tamoxifen in first-line treatment are promising. The finding that exemestane may also work in patients previously exposed to nonsteroidal aromatase inhibitors reveals lack of complete cross-resistance between the compounds. Currently, exemestane given as monotherapy, or in sequence with tamoxifen (2-3 + 3-2 years of tamoxifen-exemestane or 5 years of tamoxifen followed by 2 years of exemestane) is being compared with tamoxifen 5 years monotherapy in the adjuvant setting. In addition, we are currently addressing the toxicity of exemestane in a placebo-controlled trial in low-risk breast-cancer patients. The results from these studies will outline the potential role of exemestane in adjuvant treatment and, potentially, for breast-cancer prevention in postmenopausal women.
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PMID:The role of aromatase inactivators in the treatment of breast cancer. 1220 80

Given both the increase in the mean age of the population of Western countries and the high incidence of breast cancer beyond the age of 65 years, it is evident that breast cancer in older women will be a very common problem for the medical oncologist. Metastatic breast cancer is still not amenable to a cure; therefore quality of life during therapy is an important issue, which until recently has been poorly investigated. Similarly, despite recent advances in breast cancer therapy, physicians have been reluctant to enrol older patients in clinical trials, and there is a lack of data regarding this population. This review focuses on quality-of-life issues during metastatic breast cancer treatment in geriatric patients, comparing the standard therapeutic options and newer approaches. Although first-line endocrine therapy with tamoxifen remains a standard treatment, the newer third-generation aromatase inhibitors provide similar or better efficacy with fewer adverse effects and a better quality of life. It has been a common belief that chemotherapy impairs quality of life, but recent studies in advanced breast cancer have shown that this therapy has a positive effect on quality of life, at least in responders. Consequently, chemotherapy should not be denied to elderly patients with metastatic breast cancer, provided a prior geriatric assessment is performed to evaluate the risk-benefit ratio. New chemotherapy strategies, such as the taxanes and orally administered chemotherapy, represent a very attractive alternative for a better quality of life in elderly patients with metastatic breast cancer.
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PMID:Strategies for improving quality of life in older patients with metastatic breast cancer. 1220 54

Tamoxifen is a selective estrogen receptor modulator (SERM) with pro- and anti-estrogenic properties. Currently it is the most widely used agent for first line treatment against hormone sensitive metastatic breast cancer and the only approved hormonal agent for adjuvant treatment of organ confined breast cancer. Furthermore, its uses have been extended for the treatment of intraductal breast carcinoma patients. In such settings the most worrisome side effect of tamoxifen is its ability to increase the rates of uterine cancers. It has been claimed that most of these cancers are found at an early stage because of vaginal bleeding. Moreover, it has been shown that for most women transvaginal ultrasound is an ineffective screening method for the early detection of uterine carcinomas. It is important, however, to notice that long term tamoxifen treatment can cause metastatic uterine cancer--not only carcinomas but also sarcomas (mainly malignant mixed mesodermal tumors. It should be noted that, at least for the special population of BRCA mutation carriers, transvaginal ultrasound can increase our ability for the earlier discovery of ovarian cancer. Thus, we believe that there is still a place for the use of transvaginal ultrasound in special populations. This is specifically for long term tamoxifen users (more than the usually recommended five years), women with a higher chance of having uterine carcinomas (namely very high body weight, strong family history) and women with a high index of suspicion as carriers of a BRCA mutation. Until new second generation SERMs and aromatase inhibitors are shown to possess better anti-cancer abilities than tamoxifen, this drug will remain in wide use, however, we must not overlook its possible rare side effects.
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PMID:[Tamoxifen and breast cancer]. 1222 37

A wide range of endocrine therapies has demonstrated activity in the treatment of hormone receptor-positive metastatic breast cancer and sequential tumor responses to sequential hormonal therapies are common. However, the optimal sequence of the hormonal therapies has not yet been determined. The selection of endocrine therapies in women with hormone receptor-positive breast cancer is strongly influenced by the menopausal status of the patient. For premenopausal women, tamoxifen alone or combined with ovarian suppression using a luteinizing hormone-releasing hormone (LHRH) agonist - such as goserelin or leuprolide - is an appropriate first-line hormonal therapy. Ovarian ablation or megestrol acetate is an appropriate second-line hormonal therapy for premenopausal women treated with tamoxifen as first-line therapy, or ovarian ablation plus an aromatase inhibitor (AI) or megestrol acetate for women treated with first-line tamoxifen plus an LHRH agonist. For postmenopausal women, the non-steroidal AIs anastrozole and letrozole now represent the preferred first-line hormonal treatment for metastatic breast cancer, based upon both efficacy and toxicity considerations. For second-line therapy in postmenopausal women, a number of options now exist, including tamoxifen, the steroidal AI exemestane, and the new agent fulvestrant. Fulvestrant, a novel estrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, has been demonstrated to be at least as effective as anastrozole in postmenopausal women whose tumors progress on tamoxifen. The establishment of the optimal sequence of the endocrine therapies should offer significant benefits to women with hormone-sensitive metastatic breast cancer.
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PMID:Sequencing of endocrine therapies in breast cancer--integration of recent data. 1235 21

The mechanism of action, pharmacology, and clinical efficacy and safety of exemestane in the treatment of metastatic breast cancer are reviewed. Endocrine strategies that deprive tumor cells of estrogens are effective therapeutic modalities for patients with hormone-dependent breast cancer. The efficacy and toxicities associated with tamoxifen and aminoglutethimide have contributed to the development of agents that selectively target aromatase, the enzyme responsible for conversion of androgens to estrogens. Exemestane, an orally active irreversible inhibitor of aromatase, was recently approved as second-line endocrine therapy of advanced hormone-sensitive postmenopausal breast cancer. Compared with megestrol acetate in patients with disease progressing on tamoxifen, a number of clinical endpoints, including a survival advantage, were significantly better in the exemestane-treated group. Preliminary data also indicate that cross-resistance is incomplete between exemestane and the reversible aromatase inhibitors. Even though suppression of aromatase activity is quantitatively similar regardless of the interactive mechanism between drug and enzyme, clinically relevant differences may become apparent with further application of these two types of aromatase inhibitors. Exemestane is effective as a second- or third-line treatment of advanced, estrogen-receptor positive breast cancer in postmenopausal patients.
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PMID:Exemestane: treatment of breast cancer with selective inactivation of aromatase. 1245 3

Aminoglutethimide is used therapeutically as an aromatase inhibitor in the treatment of metastatic breast cancer in post-menopausal women. For doping purposes, aminoglutethimide may be used for treatment of adverse effects of an extensive abuse of anabolic androgenic steroids (gynaecomastia) and to increase the testosterone concentration and stimulation of testosterone biosynthesis. The use of aromatase inhibitors has been prohibited for male athletes since September 1, 2001. The purpose of this study was to develop methods for the identification of the parent compound or its main metabolite and the inclusion of this information into established screening procedures in doping analysis. An excretion study was conducted using oral application of one single therapeutic dose (500 mg) of Orimeten. The analysis was performed by gas chromatography/mass spectrometry (GC/MS). Aminoglutethimide is excreted almost totally as unconjugated parent compound and is detectable by different screening procedures for up to 165 h. Most suitable for the detection of aminoglutethimide is the screening procedure for heavy volatile nitrogen-containing drugs ('Screening 2'). However, since only competition samples are analysed in that screening procedure, the additional inclusion of aminoglutethimide in the screening procedure for anabolic androgenic agents ('Screening 4') is recommended. Full mass spectra and diagnostic ions for the analysis of aminoglutethimide are presented.
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PMID:Identification of the aromatase inhibitor aminoglutethimide in urine by gas chromatography/mass spectrometry. 1247 62

Endocrine therapy remains an important approach to the treatment of metastatic breast cancer because of its effectiveness and excellent tolerability. In the last 10 years, a number of new endocrine therapies have been introduced. These include the luteinizing hormone-releasing hormone agonists, which produce menopausal changes in premenopausal women; the aromatase inhibitors, which prevent production of estrogen in postmenopausal women; and the estrogen receptor down-regulator fulvestrant (Faslodex), which is effective in postmenopausal women whose tumors have progressed following response to other selective estrogen receptor modulators. The endocrine cascade for the treatment of premenopausal women with metastatic disease now involves the concurrent or sequential combination of a luteinizing hormone-releasing hormone analogue and tamoxifen, whereas the cascade for the treatment of postmenopausal women can begin with tamoxifen followed by an aromatase inhibitor or with an aromatase inhibitor followed by tamoxifen. The optimal cascade following the use of an aromatase inhibitor and tamoxifen in postmenopausal women remains unclear, but fulvestrant and megestrol acetate or the use of an aromatase inactivator (exemestane) following an aromatase inhibitor are all available options with some activity. Over the next few years, clinical trials will clarify the optimal sequence of endocrine therapy for postmenopausal women. The use of estrogen and progesterone receptor status to select for endocrine therapy is undeniably crucial. HER2/neu overexpression may also predict response to endocrine therapy, but this remains controversial.
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PMID:Endocrine therapy of advanced disease: analysis and implications of the existing data. 1253 1

In the United States, three third-generation aromatase inhibitors are available commercially: anastrozole, letrozole, and exemestane. Anastrozole and letrozole are nonsteroidal agents, whereas exemestane is a steroid. The three agents differ in terms of structure and metabolic products and in the degree to which they suppress aromatase activity. The clinical significance of these differences is unclear. All three of the agents have been found to be equivalent or superior to megesterol acetate as a second-line therapy for metastatic breast cancer. In the first-line setting, large Phase III trials have demonstrated that anastrozole and letrozole are equivalent or superior to tamoxifen in women with metastatic disease. Multiple trials with widely varying study designs have been launched in the adjuvant setting comparing the aromatase inhibitors to tamoxifen. Early results from the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial suggest a small but statistically significant improvement in disease-free survival for anastrozole compared with tamoxifen, but further follow-up is needed. This article explores the efficacy and tolerability of the aromatase inhibitors in both the metastatic and the adjuvant settings.
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PMID:Clinical differences among the aromatase inhibitors. 1253 3


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