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

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

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

Breast cancer is the most frequently diagnosed malignancy in American women. Although potentially curable in the early stage, metastatic breast cancer, however, is essentially incurable. Because metastatic breast cancer is unlikely to be cured with currently available therapies, the goals of treatment in this setting are prolonging survival and maintaining or improving the quality of life. In patients with receptor (estrogen or progesterone)-positive metastatic breast cancer, endocrine therapy is generally considered the preferred first-line therapy because of the superior tolerability and the similar efficacy when compared with chemotherapy. Today a variety of endocrine therapies are available for the treatment of metastatic breast cancer, among which tamoxifen is the most widely used. Despite its proven efficacy and safety, a significant proportion of patients do not respond to tamoxifen. Further, due to its partial estrogenic activity, tamoxifen is associated with an increased risk of thromboembolism and endometrial cancer. Agents without any estrogenic activity-estrogen receptor downregulators have therefore been developed. Fulvestrant is the first clinically proven agent of this class. Oncology nurses have a key role in managing and educating patients with breast cancer. This supplement provides nurses with an overview of existing and emerging endocrine therapies for postmenopausal patients with metastatic or advanced breast cancer.
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PMID:Estrogen receptor downregulators: new advances in managing advanced breast cancer. 1208 May 37

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

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

Patients with hormone-sensitive breast cancer who have responded to tamoxifen may receive additional benefit from a second endocrine agent following progression or relapse after tamoxifen therapy. Fulvestrant (Faslodex((R)), ICI 182780, AstraZeneca Pharmaceuticals; Wilmington, Delaware) is a selective antagonist of estrogen designed to have no estrogenic effects. Lack of aqueous solubility led to the development of a parenteral formulation for monthly intramuscular administration. Fulvestrant has been shown to inhibit the proliferative effects of estrogen on sensitive tissues in vitro and in vivo, and is without apparent measurable estrogenic activity. The data upon which marketing approval for fulvestrant was based are summarized below. Eight hundred fifty-one postmenopausal women with advanced breast cancer were enrolled in two phase III studies, 400 in a North American double-blind study and 451 in a European open-label study, comparing the efficacy and safety of fulvestrant with anastrozole. Four hundred twenty-eight patients were randomized to receive fulvestrant 250 mg monthly by intramuscular injection and 423 patients were to receive anastrozole 1 mg daily. Patients were considered hormone sensitive either by receptor status or previous response to endocrine therapy. Over 96% of patients had previously received tamoxifen, either in the adjuvant setting or as treatment for metastatic disease. The primary study end points were response rate and time to progression. Response rates for patients treated with fulvestrant were 17% and 20% in the North American and European trials, respectively, compared with 17% and 15% in the anastrozole treatment arms. There were no statistically significant differences in response rates, time to progression, or survival between treatment arms in either study. The most common adverse events attributed to the treatment (>10%) were injection-site reactions and hot flashes. Common events (1%-10%) included asthenia, headache, and gastrointestinal disturbances (nausea, vomiting, and diarrhea), as well as rash and urinary tract infections. A small increase in joint disorders was reported in the anastrozole-treated patients. On April 25, 2002, fulvestrant 250 mg by monthly intramuscular injection was approved by the U.S. Food and Drug Administration for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Approval was based on similarity of response rates and time to progression between fulvestrant and anastrozole.
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PMID:FDA drug approval summaries: fulvestrant. 1249 Jul 35

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

Since its introduction more than 30 years ago, tamoxifen has been the most widely used endocrine therapy for the treatment of women with advanced breast cancer. More recently, a number of alternative endocrine treatments have been developed, including several selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and, most recently, fulvestrant ('Faslodex'). Fulvestrant is an estrogen receptor (ER) antagonist, which, unlike the SERMs, has no known agonist (estrogenic) effect and downregulates the ER protein. Tamoxifen is effective and well tolerated, although the non-steroidal AIs, anastrozole and letrozole, are more effective treatments for advanced disease than tamoxifen. Fulvestrant has recently gained US Food and Drug Administration approval for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. In two global phase III clinical trials fulvestrant was at least as effective and as equally well tolerated as anastrozole for the treatment of postmenopausal women with advanced and metastatic breast cancer. In a retrospective analysis of the combined data from these trials, mean duration of response was significantly greater for fulvestrant compared with anastrozole. These new hormonal treatments expand the choice of endocrine therapy for women with advanced breast cancer and offer new options for sequencing and combining treatments.
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PMID:Fulvestrant ('Faslodex')--a new treatment option for patients progressing on prior endocrine therapy. 1254 3

Fulvestrant, the first drug of the pure estrogen antagonists to be approved for clinical use, is a new therapeutic option for metastatic breast cancer. Fulvestrant offers a unique metastatic breast cancer treatment option because its mechanism of action is the destruction, rather than the blockade, of estrogen receptors. No known agonistic activity exists, limiting potential side effects and receptor exhaustion. The side effect profile of fulvestrant is related to its antiestrogen effect and includes gastrointestinal disturbance, urinary tract infection, and vaginitis. Suggestions for managing the side effects of fulvestrant are described, and a case study is provided as an illustrative aid in understanding the role of this new hormonal agent.
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PMID:Hormonal therapy for breast cancer: focus on fulvestrant. 1279 37

For the past 25 years, the estrogen antagonist tamoxifen has been the hormonal treatment of choice for postmenopausal patients with hormone-sensitive metastatic and early breast cancer (EBC). However, tamoxifen is associated with certain tolerability and safety concerns. In addition, the hormonal options after progression are limited, and thus, alternative endocrine treatments have been developed. This review provides a synopsis of the newer alternatives in endocrine therapy of breast cancer: the aromatase inhibitors (AIs) and fulvestrant Faslodex), the estrogen receptor antagonist that downregulates estrogen and progesterone receptors and has no known agonist activity. The third-generation AIs, anastrozole and letrozole, have been shown to be as effective or more effective than megestrol acetate and tamoxifen as second- and first-line therapies for the treatment of postmenopausal patients with metastatic breast cancer, and exemestane has been approved for second-line use. Fulvestrant has been shown to be as effective as anastrozole as second-line therapy for metastatic breast cancer and has been approved in the U.S. for the treatment of postmenopausal women with hormone-receptor-positive metastatic breast cancer following progression on antiestrogen therapy. Anastrozole is the only AI with published clinical trial data and U.S. Food and Drug Administration approval for adjuvant therapy of postmenopausal women with EBC. The 'Arimidex,' Tamoxifen, Alone or in Combination (ATAC) trial, a double-blind, multicenter trial with 9,366 patients, compared tamoxifen with anastrozole, alone and in combination, as adjuvant endocrine treatment for postmenopausal patients with operable, invasive, EBC. The first analysis (at a median follow-up of 33.3 months) showed longer disease-free survival and, in general, better tolerability with anastrozole than with tamoxifen. This pattern was maintained at later analyses with a median follow-up of 47 months for efficacy and 37 months for safety and tolerability. Although longer follow-up is warranted, anastrozole appears to be a well-documented choice of endocrine adjuvant therapy for postmenopausal women with hormone-responsive breast cancer.
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PMID:Advances in endocrine treatments for postmenopausal women with metastatic and early breast cancer. 1289 30


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