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

We compared the efficacy and safety of the oral aromatase inactivator exemestane (EXE) with megestrol acetate (MA) in women with metastatic breast cancer. This phase III randomized, double-blind, multicenter study was conducted in 769 postmenopausal women who had experienced tamoxifen failure. Treatment arms consisted of EXE 25 mg once daily (n=366) or MA 40 mg four times daily (160 mg daily; n=403). Peer-reviewed, intent-to-treat analyses demonstrated that EXE induced a trend toward higher rates of complete response (CR)+partial response (PR) (15.0% vs. 12.4%) and of CR+PR+stable disease (SD)=24 weeks (37.4% vs. 34.6%), but differences were not statistically significant. Statistically significant differences favoring EXE were seen in median duration of CR+PR+SD=24 weeks (60.1 vs. 49.1 weeks; P=0.025), time to tumor progression (20.3 vs. 16.6 weeks; P=0.037), time to treatment failure (16.3 vs. 15.7 weeks; P=0.042), and overall survival (not reached vs. 123.4 weeks; P=0.039). Both treatments were well tolerated, but MA was associated with more grade 3 or 4 weight gain (8% vs. 17%, P=0.001); the pain score was sim-ilar in both groups. There was a trend toward superiority in treatment-related signs and symptoms (TRSS) with EXE. There was greater improvement in the pain score and TRSS in patients achieving an objective response with EXE vs. MA. Quality of life improved or was similar for EXE in most domains. Exemestane offers an important new treatment option for postmenopausal women with hormone-responsive breast cancer.
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PMID:Exemestane improves survival in metastatic breast cancer: results of a phase III randomized study. 1197 Jul 44

Over the last 30 years the role of tamoxifen in breast cancer treatment has been progressively expanded by clinical investigation to encompass the entire spectrum of disease from cancer chemoprevention to palliation of advanced disease. The primacy of tamoxifen for these indications in postmenopausal women is now under challenge by the selective aromatase inhibitors, a class of endocrine agent that induces oestrogen deprivation rather than oestrogen receptor blockade. This review considers the biochemical, pharmacological and clinical properties of the nonsteroidal aromatase inhibitor letrozole. This agent is superior to tamoxifen for the treatment of metastatic breast cancer, a finding that suggests that letrozole may ultimately eclipse tamoxifen for other indications, including chemoprevention. Further clinical investigation will be necessary to establish the risks and benefits of letrozole versus tamoxifen for each new indication, with adjuvant therapy being the next in line. The object of this review is to provide a reference source on the biochemical, pharmacological and clinical properties of letrozole for clinicians to consider both established and future indications.
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PMID:Letrozole in the treatment of breast cancer. 1199 38

Exemestane is a new oral steroidal aromatase inactivator, active in postmenopausal women with hormonal sensitive breast carcinoma. This drug, at a dosage of 25 mg once daily, was shown to suppress in vivo aromatase activity by 97.9%, with a subsequent reduction superior to 85% of circulating oestrogen level. It exhibits definite antitumor activity at a relatively low daily dose, and is highly potent, highly selective, and well-tolerated. Moreover, for postmenopausal women with metastatic breast cancer, exemestane demonstrated a higher activity and lower toxicity profile when compared to megestrol acetate and tamoxifen in second- and first-line therapy, respectively. New data on exemestane are forthcoming both in the adjuvant and neoadjuvant setting, which could improve the management of early breast cancer in the future.
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PMID:Current status and future potential role of exemestane in the treatment of early and advanced breast cancer (Review). 1201 11

The goal of adjuvant hormonal therapy is to prevent breast cancer recurrence. Standard therapy with tamoxifen has shown great value in the adjuvant setting; however, its tolerability profile can render it unsuitable for some patients. The aromatase inactivator, exemestane, and the 2 aromatase inhibitors, letrozole and anastrozole, have been shown to be equivalent or superior to tamoxifen with respect to multiple endpoints in patients with metastatic breast cancer. With tolerability profiles that are similar to, and in many cases, more acceptable than that of tamoxifen, and efficacy potentially superior to tamoxifen, studies using the antiaromatase agents as adjuvant therapy are currently ongoing. These trials will answer some important questions, such as the order in which adjuvant hormonal therapies are selected to maximize efficacy, whether the antiaromatase agents show improved tolerability, and whether combination therapy is more effective than monotherapy.
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PMID:Antiaromatase agents: evolving role in adjuvant therapy. 1202 Mar 94

Aromatase inhibitors and inactivators are increasingly important to the therapy of advanced breast cancer in postmenopausal women. These compounds are also currently being evaluated in the adjuvant setting and may have potential in breast cancer prevention. In addition to the recent clinical results, experimental research with development of aromatase 'knockout' mice as well as certain clinical observations in individuals lacking this enzyme have deepened our understanding of estrogens outside of the field of reproduction. Such information should help us to further develop this type of therapy in breast cancer and, in particular, extend our understanding of the lack of complete cross-resistance between aromatase inhibitors and inactivators. Clinically, third-generation aromatase inhibitors and inactivators have shown superiority compared with conventional treatment in advanced postmenopausal breast cancer with respect to second-line (tamoxifen failures) as well as first-line therapy. The fact that tamoxifen is noncurative in metastatic disease but improves long-term survival in the adjuvant setting suggests that even modest improvements in therapy of advanced disease may be translated into survival benefits in patients with early disease. In addition, these novel compounds with lack of complete cross-resistance extend the scope of using sequential treatment options to maximise the duration of optimal endocrine therapy in metastatic breast cancer disease.
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PMID:Aromatase inhibitors and inactivators for breast cancer therapy. 1203 79

More than 40,000 women in the United States die each year from metastatic breast cancer. Elucidation of HER2 and its role in malignant transformation has helped define a subset of aggressive breast cancer that may be relatively resistant to non-anthracycline-based therapies and hormonal agents, but responds to targeted molecular therapy. Trastuzumab, an antibody against HER2, has proven effective as single agent therapy in women with HER2 overexpressed metastatic breast cancer. Moreover, in combination with chemotherapy, trastuzumab has been shown to delay disease progression and improve overall survival for women with HER2-positive advanced breast cancer. The combination of chemotherapy and trastuzumab is emerging as a standard of care in women with HER2 overexpressed metastatic breast cancer. Several combination regimens using trastuzumab with taxanes, vinca alkaloids, or platinum compounds have demonstrated efficacy in first- and second-line treatment settings. However, the development of anthracycline-based combinations has been limited by concerns of related cardiotoxicity. Newer multi-agent regimens are in development. The optimal combination, duration, and sequence of trastuzumab therapy remain unknown in patients with HER2-positive metastatic disease. The role of continuing treatment after disease progression is also unclear. Evidence from some retrospective analyses suggest HER2-positive tumors are relatively resistant to tamoxifen and perhaps more responsive to aromatase inhibitors, although such data are inconclusive. HER2 status should not be used routinely for clinical decision making regarding hormonal therapy options. Several ongoing trials are attempting to address these and other issues related to HER2 testing to select the most appropriate candidates for these emerging therapies. While many questions remain, the treatment of HER2 overexpressing metastatic breast cancer is rapidly evolving, and represents a new approach to treatment in oncology.
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PMID:HER2 overexpressing metastatic breast cancer. 1205 79

Hormone therapy is the most important systemic treatment of hormone receptor-positive breast cancer at all stages. Selective oestrogen receptor modulators (SERMs), such as tamoxifen, the mainstay of hormone receptor positive breast cancer manipulation for many years, are limited by their agonist actions. Oestrogen-like activity of these drugs may stimulate cancer growth such as in the endometrium and is a mechanism of resistance in breast cancer. Fulvestrant, the first of a new class of drugs, an oestrogen receptor down regulator, may have advantages over tamoxifen in the treatment of oestrogen-dependent disease. The pre-clinical development and early clinical data of fulvestrant are reviewed. Fulvestrant was as effective as the aromatase inhibitor anastrazole in second-line advanced breast cancer. The phase III trial of fulvestrant versus tamoxifen, as first-line treatment for metastatic breast cancer, has completed accrual and is maturing. Fulvestrant has useful activity against breast cancer as well as a favourable side-effect profile and is likely to represent a useful addition to the fight against hormone dependent breast cancer. Its place will be better defined by ongoing clinical trials.
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PMID:Fulvestrant: a review of its development, pre-clinical and clinical data. 1207 16

Endocrine therapy is first-line therapy for patients with estrogen receptor-positive or progesterone receptor-positive metastatic breast cancer. Commonly used endocrine therapies are tamoxifen, megestrol acetate, and aromatase inhibitors. Although tamoxifen and megestrol acetate have a favorable therapeutic profile, there are risks associated with these agents. With tamoxifen, the partial agonist property can lead to thromboembolic events. An important adverse event of megestrol acetate is weight gain and fluid retention in some patients. The aromatase inhibitors are currently used as second-line therapy after tamoxifen failure. A recent study showed that anastrozole, an aromatase inhibitor, is as effective or even superior to tamoxifen when used as a first-line therapy. However, not all patients will respond to currently available therapies. A new class of drug, the estrogen receptor downregulators, has been developed. Fulvestrant, the first agent in this new class, not only induces the degradation of the estrogen receptor but also is an estrogen antagonist; further, its lack of agonist activity provides a better safety profile. Two phase III trials have proven that fulvestrant is at least as effective as anastrozole in postmenopausal women with advanced breast cancer. Fulvestrant is an effective and safe endocrine therapy for postmenopausal women who have failed prior endocrine therapy.
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PMID:Existing and emerging endocrine therapies for breast cancer. 1208 May 38

The aromatase enzyme converts androgens to estrogens and is the therapeutic target for aromatase inhibitors in postmenopausal patients with estrogen receptor-positive metastatic breast cancer. Third-generation inhibitors such as letrozole are being considered as potential prophylactic agents for breast cancer. The rationale for their preventive application would be aided by knowledge of their effects on the normal breast and on other estrogen-dependent processes such as bone and lipid metabolism. Thirty-two women without active breast disease were recruited to 3-month treatment with letrozole (2.5 mg/day). Core-cut biopsies from the breast and blood samples were collected before and at the end of treatment. Plasma estradiol levels were markedly suppressed in all but two patients, who were excluded from the efficacy assessment. There was no significant change in the proliferation marker Ki67 (mean change, -23%; 95% confidence interval, -50% to +23%) or estrogen receptor in breast epithelial cells with treatment. Similarly, there were no significant changes in plasma levels of insulin-like growth factor I or lipid profiles. However, there was a significant increase (25%) in the levels of the bone resorption marker C-telopeptide crosslinks (CTx). We conclude that any prophylactic effect of letrozole is not likely to be dependent on antiproliferative effects on normal breast. Studies in healthy patients will need to recognize the potential for enhanced bone resorption.
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PMID:Effects of the aromatase inhibitor letrozole on normal breast epithelial cell proliferation and metabolic indices in postmenopausal women: a pilot study for breast cancer prevention. 1210 Nov 8

The aromatase inhibitors are established first-line drugs for treating metastatic breast cancer in postmenopausal women, and are gaining acceptance as adjuvant treatment as well.
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PMID:Aromatase inhibitors in breast cancer: current and evolving roles. 1210 40


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