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

In spite of major advances in early detection and adjuvant therapy, metastatic breast cancer remains a major clinical problem affecting a significant number of patients. Metastatic disease is generally considered incurable and conventional therapy is used mainly with palliative intent. Therefore, the choice of appropriate therapeutic approach requires a reasoned evaluation of the likelihood of benefit from therapy balanced with the impact of therapy on the patient's quality of life. The estimated aggressiveness of the tumour and indicators of response to therapy (e.g. the status of hormonal receptors) are useful parameters to take into account before selecting a given treatment. Endocrine therapy is an important option in the management of stage IV disease, with tamoxifen the most widely used first-line drug in postmenopausal women. For progressing patients, the third generation of aromatase inhibitors (letrozole, anastrazole) are considered good second-line endocrine agents. The LH-RH agonists represent the initial choice in premenopausal patients candidate to receive hormonal therapy, with the use of tamoxifen as a valuable alternative. Combination chemotherapy regimens (e.g. CMF or CAF) are usually used for first-line treatment of patients with aggressive, steroid receptor-negative disease. Recently, several relatively new agents have shown significant activity in metastatic breast cancer. In particular, the taxanes (paclitaxel and docetaxel) are particularly promising as single agents but also in combination with other drugs, especially anthracyclines. Finally, another class of agents, the d mention because they represent an important new treatment modality in the management of metastatic.
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PMID:[Treatment of metastatic breast carcinoma]. 1046 41

Aromatase inhibitors were first reported in the early 1970s and have been used to treat breast cancer since that time. Until recently, essentially the only agent available in this class was aminoglutethimide, a nonspecific inhibitor with multiple adverse effects and drug interactions. Selective and potent aromatase inhibitors are now available (formestane, exemestane, fadrozole, anastrozole and letrozole), and we review the risks and benefits of these agents in order to assist clinicians in making treatment decisions. Formestane is an injectable steroidal aromatase inhibitor with significant activity against metastatic breast cancer. It has been shown to have similar efficacy and superior tolerability compared with megestrol, and is similar to tamoxifen in the metastatic setting. Exemestane is an oral steroidal aromatase inhibitor. It has been shown to be effective third-line therapy after tamoxifen and megestrol in postmenopausal patients with metastatic breast cancer. All the nonsteroidal (imidazole/triazole) aromatase inhibitors are orally available. Fadrozole has similar activity to megestrol and tamoxifen in the setting of metastasis, but has been shown in phase II trials to inhibit cortisol and aldosterone production. Anastrozole and letrozole have similar toxicity profiles. Compared with megestrol, anastrozole improves overall survival and has superior tolerability. Letrozole is superior to megestrol and aminoglutethimide in terms of overall survival and time to progression, and is also better tolerated. Although there is a strong rationale for using these agents in the treatment of breast cancer, the information presently available is insufficient to recommend any one agent over another. Direct comparative studies are lacking, and comparing agents across studies is limited by many biases and may not be valid. Formestane is only available as an injection and exemestane is not commercially available in many countries, making these agents more difficult to recommend over the other 3 agents. Fadrozole is less potent and less selective in inhibiting aromatase than letrozole. The efficacies of fadrozole, megestrol and tamoxifen appear to be similar; however, comparative data show no advantage of fadrozole over letrozole. Anastrozole and letrozole are generally considered to be similar agents. The clinical future of the selective aromatase inhibitors is promising, and these agents may change the way postmenopausal breast cancer is treated at all stages of the disease.
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PMID:Risks and benefits of aromatase inhibitors in postmenopausal breast cancer. 1051 21

Aromatase, a cytochrome P-450 enzyme that catalyzes the conversion of androgens to estrogens, is the major mechanism of estrogen synthesis in the post-menopausal woman. We review some of the recent scientific advances which shed light on the biologic significance, physiology, expression and regulation of aromatase in breast tissue. Inhibition of aromatase, the terminal step in estrogen biosynthesis, provides a way of treating hormone-dependent breast cancer in older patients. Aminoglutethimide was the first widely used aromatase inhibitor but had several clinical drawbacks. Newer agents are considerably more selective, more potent, less toxic and easier to use in the clinical setting. This article reviews the clinical data supporting the use of the potent, oral competitive aromatase inhibitors anastrozole, letrozole and vorozole and the irreversible inhibitors 4-OH androstenedione and exemestane. The more potent compounds inhibit both peripheral and intra-tumoral aromatase. We discuss the evidence supporting the notion that aromatase inhibitors lack cross-resistance with antiestrogens and suggest that the newer, more potent compounds may have a particular application in breast cancer treatment in a setting of adaptive hypersensitivity to estrogens. Currently available aromatase inhibitors are safe and effective in the management of hormone-dependent breast cancer in post-menopausal women failing antiestrogen therapy and should now be used before progestational agents. There is abundant evidence to support testing these compounds as first-line hormonal therapy for metastatic breast cancer as well as part of adjuvant regimens in older patients and quite possibly in chemoprevention trials of breast cancer.
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PMID:Use of aromatase inhibitors in breast carcinoma. 1073 91

BACKGROUND: There has been an explosion in the development of hormonal therapies for the treatment of breast cancer. Several new agents have been approved for the treatment of breast cancer in the metastatic setting, and trials are ongoing in the adjuvant and prevention setting to improve hormonal therapy for the prevention and treatment of breast cancer. METHODS: The literature on new hormonal therapies for the treatment of breast cancer is reviewed, with an emphasis on newer agents. RESULTS: Two antiestrogens are now approved in the United States for the treatment of metastatic breast cancer. Other antiestrogens have activity in metastatic breast cancer as well as in osteoporosis. Newer pure antiestrogens may overcome resistance to tamoxifen. Several aromatase inhibitors are available for the treatment of metastatic breast cancer. CONCLUSIONS: Many hormonal agents are now available for both adjuvant and advanced disease settings. Developments will depend on clarifying mechanisms of resistance to antiestrogens and identifying new classes of agents that lack cross-resistance to standard therapy.
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PMID:New Hormonal Therapies for Breast Cancer. 1075 54

Complete estrogen blockade has long been sought as a more effective means of controlling breast cancer compared with single agent endocrine therapy. This approach may be accomplished through the use of agents which reduce estrogen production combined with agents that prevent the activity of estrogen at the cellular level. For prostate cancer, another hormonally responsive malignancy, this approach has not been successful at improving survival compared with that achieved with single agent therapy. Preclinical information is contradictory for many promising combinations and may not reflect the true nature of in vivo interaction between agents. For premenopausal patients with metastatic breast cancer, the combination of a luteinising hormone-releasing hormone (LHRH) agonist and tamoxifen is clearly effective, but whether the combination is more effective than either single agent is still controversial. Similar response rates and overall survival were reported with goserelin or goserelin plus tamoxifen by Jonat et al. in 1 randomised, prospective study, but the addition of tamoxifen improved time to progression. A second trial comparing buserelin plus tamoxifen with either single agent reported superior efficacy in terms of response rates, disease-free survival and overall survival with combination therapy. A meta-analysis of 4 randomised trials making similar comparisons, demonstrated significant improvement in median overall survival, progression-free survival, response rate, and duration of response with the combination of a LHRH agonist (goserelin or buserelin) and tamoxifen in premenopausal breast cancer patients with metastatic disease. For postmenopausal women with metastatic breast cancer, the addition of an aromatase inhibitor to tamoxifen has yet to be prospectively compared to single agent therapy. Use of endocrine combinations in the treatment of early stage breast cancer is under investigation. Preliminary results of some of the ongoing adjuvant therapy trials indicate that the combination of a LHRH agonist and tamoxifen may have similar efficacy to cyclophosphamide, methotrexate, and fluorouracil chemotherapy in premenopausal women with estrogen receptor-positive tumour. Addition of LHRH agonist therapy in premenopausal patients with estrogen receptor-positive tumour who had maintained the ovarian function following chemotherapy [cyclophosphamide, doxorubicin (adriamycin), fluorouracil, and tamoxifen], also led to a reduction in the risk of recurrence. These studies have identified a sub-population of patients who may benefit from the addition of combination endocrine therapy. Overall, the issue is quite complex and the data from many ongoing trials are still awaited with anticipation to further delineate the role of complete estrogen deprivation in this disease.
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PMID:Complete estrogen blockade for the treatment of metastatic and early stage breast cancer. 1087 21

The efficacy of combined endocrine therapy with tamoxifen (TAM), aminoglutethimide (AG), and hydrocortisone (H) or tamoxifen and fluoxymesterone (FLU) was evaluated against treatment with tamoxifen alone in 311 patients above 65 years of age with a first recurrence of a metastatic breast cancer. A total of 279 patients were eligible. The response rates were assessed for 258 fully evaluable patients and were the following for the TAM (N = 94), the TAM+AG+H (N = 83), and the TAM+FLU (N = 81) groups, respectively, PR: 14, 18, and 21%, and CR: 20, 11, and 23%. The overall response rates are not statistically different (p = 0.30). The 95% CL of difference in response rates for TAM vs. TAM+AG+H are -9-19% and for TAM vs. TAM+FLU -4-25%. Time to treatment failure was comparable with median values of 9.2, 7.7, and 9.2 months in the TAM, TAM+AG+H, and TAM + FLU group, respectively (p = 0.17). The corresponding figures for survival are median times of 22.0, 24.1, and 21.1 months with a p-value of 0.62. Toxicity was more pronounced in both the combined treatment groups, and could in most instances be attributed to treatment with either AG+H or FLU. Currently, new specific aromatase inhibitors with lesser toxicity than AG are being evaluated in combination with TAM for treatment of primary and metastatic breast cancer. In conclusion, the simultaneous use of TAM and AG +H or FLU does not seem to improve the therapeutic efficacy in elderly postmenopausal patients with metastatic disease. So far, combined endocrine therapy in this group of patients should only be used in the context of clinical trials.
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PMID:Combined endocrine treatment of elderly postmenopausal patients with metastatic breast cancer. A randomized trial of tamoxifen vs. tamoxifen + aminoglutethimide and hydrocortisone and tamoxifen + fluoxymesterone in women above 65 years of age. 1094 95

Progesterone antagonists (PAs) (antiprogestins) or progesterone receptor modulators (PRMs) form an interesting category of new hormonal agents in the treatment of breast cancer. In vitro, antiproliferative effects of different PAs are mainly observed in estrogen-stimulated growth of PR-positive tumor cell lines. Both progestin agonist/antagonist actions on mammary tumor cells are dependent on the type of cell line, culture medium and concentrations of the PAs used, and type of biologic response measured. In various experimental animal tumor models, different PAs showed a greater antitumor activity than tamoxifen or high-dose progestins. Most interestingly, combination treatment of different PAs (mifepristone, ORG 31710, onapristone) or PRMs with different antiestrogens (tamoxifen, droloxifen, ICI 164384) or with an aromatase inhibitor (atemestane) showed greater antitumor efficacy than treatment with each single type of drug alone. These additive antiproliferative effects were demonstrated in various experimental in vitro and in vivo models. In some studies, these effects were accompanied by additive effects on several cell biologic parameters. In pretreated postmenopausal patients with metastatic breast cancer, objective responses have been observed in 10-12%, and stable disease in 42-46% of the patients; in previously untreated patients objective response rates of 11 and 56% have been reported. The clinical development of onapristone was stopped because of liver toxicity. At the present time, apart from development of new pure potent PAs, clinical investigation of combined therapy of PAs with antiestrogens are urgently needed.
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PMID:Progesterone antagonists and progesterone receptor modulators in the treatment of breast cancer. 1110 94

In patients with metastatic breast cancer, second-line therapy with aromatase inhibitors can improve survival in comparison with megestrol. We conducted a meta-analysis to assess the effectiveness of aromatase inhibitors versus megestrol. After a Medline search, three trials (evaluating letrozole, anastrozole or exemestane versus megestrol) were included in the survival meta-analysis. Our methodology retrieved patient-level information on survival. In comparison with megestrol, aromatase inhibitors prolonged survival at levels of statistical significance (relative death risk for oral aromatase inhibitors=0.79, 95% confidence interval 0.69-0.91; p=0.0011). A lifetime analysis of the pooled survival curves of aromatase inhibitors versus megestrol found a mean survival gain of 4.1 months per patient. Aromatase inhibitors confer a significant survival benefit to patients with metastatic breast cancer as compared with megestrol. A preliminary calculation of the cost per life year gained shows that the pharmacoeconomic profile of these drugs is favorable.
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PMID:Survival in patients with metastatic breast cancer: analysis of randomized studies comparing oral aromatase inhibitors versus megestrol. 1112 31

Experimental and epidemiological studies have pointed to a major role of estrogens in the pathogenesis of human breast cancer. The Oxford meta-analysis (1998) once again confirmed the efficacy of antiestrogens (tamoxifen) as adjuvant therapy. We need to know whether the new non-steroid antiestrogens (idoxifen, droloxifen and TAT-59) and selective estrogen receptor modulator (raloxifen), whith preclinical characteristics better than those of tamoxifen will be more efficient clinically. Large-scale trials to compare the new drugs with tamoxifen are under way. Faslodex, a pure antiestrogen, looks highly promising, too. Zoladex, a luteinising hormone-releasing hormone agonist, is looking as a better choice than ovariectomy or irradiation of the pelvis for ovarian ablation in premenopausal breast cancer. New aromatase inhibitors are more efficient than progestins and much safer than aminoglutethimide. It has been shown recently that these inhibitors keep metastatic breast cancer at bay longer, and with longer survival. The non-steroid inhibitors (anastrozole and letrozole) and the steroid oral drug exemestane are undergoing clinical trials as means of adjuvant treatment of breast cancer. The trial of arimidex and tamoxifen administered alone or in combination (ATAC) is unique since it is using a combination of tamoxifen and an aromatase inhibitor (anastrozole). New methods of endocrine therapy have resulted in less toxic and more convenient procedures. Also, longer therapeutic effects and survival are becoming more apparent.
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PMID:[Modern approaches to hormone therapy of breast cancer as a reflection of pathogenesis of the disease]. 1138 56

This article reviews recent advances in the treatment of metastatic breast cancer, in particular the results of randomized controlled phase III clinical trials. These have led to the evidence-based introduction of several new drugs including aromatase inhibitors, taxanes and bisphosphonates, some of which have been shown to impact on overall survival.
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PMID:Systemic treatment of metastatic breast cancer. 1138 90


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