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

Tamoxifen is an oral antiestrogen first used in metastatic breast cancer in the early 1970s. Large clinical trials were initiated in the late 1970s and early 1980s to test the drug's role as adjuvant therapy in early stage breast cancer. Observations of marked decreases in the development of contralateral breast cancer among tamoxifen recipients suggested potential for the drug in chemoprevention of breast cancer, and a large clinical trial to test the efficacy of tamoxifen in prevention of invasive breast cancer among women at increased risk was implemented in the United States in 1992. This paper reviews the rational for the clinical studies of tamoxifen as a chemopreventive agent for breast cancer and summarizes new information that has contributed to our understanding of tamoxifen's actions at the molecular and clinical levels. Current knowledge about the drug's mechanism of estrogenic and antiestrogenic action and its beneficial effects on blood lipids and bone metabolism will be presented. Recent research findings about DNA adduct formation and hepatic lesions, tamoxifen-associated gynecologic conditions, and the occurrence of second primary cancers in other organ systems will also be discussed.
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PMID:Tamoxifen's role in chemoprevention of breast cancer: an update. 853 9

Hormonal manipulation is currently the mainstay of palliative care for metastatic breast cancer because it is well tolerated and produces significant responses in approximately one-third of unselected patients. Tamoxifen, a nonsteroidal antiestrogen, is currently considered first-line therapy. Second-line agents include progestins and aromatase inhibitors. New agents, such as the "pure" antiestrogens and the gonadotropin-releasing hormone (GnRH) agonists, are being tested. Other approaches for affecting the hormonal milieu are also under investigation, including combinations of hormonal agents, hormonal agents plus biologics, and hormonal agents plus antiproliferative agents. This review will address the basis for endocrine therapy and possible mechanisms of hormonal resistance, currently available agents and newer ones on the horizon, and areas of future interest.
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PMID:Current status of endocrine therapy for metastatic breast cancer. 856 27

Tamoxifen (T) is the mainstay of hormonal treatment and is able to give high response rates in selected postmenopausal women with advanced breast cancer (ABC). Nevertheless, even in responders, invariably resistance to hormones is developed. In a previous paper we reported that in a subset of patients (pts) with metastatic breast cancer the resistance to the antiestrogen could be overcome by pretreatment with natural interferon-beta (nIFN-beta) followed by the association of nIFN-beta and T. In the present study we adopted a treatment schedule employing nIFN-beta (3 x 10(6) IU/day im three times a week) and T (60 mg/day) concurrently in 30 pts with ABC progressive to previous treatment with T (30 mg/day). We obtained a 13% response rate with a median duration of response of 8 months (range 4-16 m). All the responses occurred in pts whose disease progressed after an initial response to T. Stabilisation of disease was observed in 37%. Toxicity was mild. In our opinion the use of the combination T plus nIFN-beta in the treatment of breast cancer remains investigational and the optimal scheduling still undetermined.
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PMID:Natural interferon-beta and tamoxifen in hormone-resistant patients with advanced breast cancer. 857 22

By the end of the 20th century, more than 50% of new breast cancer patients will be greater than 65 years old. Until recently, research focused on this older group of women has been minimal. Previous studies have indicated that the elderly are less likely to be screened, and have lesser and frequently inferior treatment. In contrast, the few clinical trials focusing on the elderly suggest that they do as well with surgery, radiation, and standard chemotherapy regimens as their younger counterparts. Comorbidity is, however, more common in older women, and must be factored into treatment and prognosis. The available data indicate that mammography should be used on a yearly to every-other-year basis for screening older women, including those older than 70 years and in fair to good health. Older women should offered breast preservation options and should receive breast radiation following lumpectomy. Tamoxifen may be used as initial therapy for frail women with early to late stage breast cancer, but is inferior to surgery in achieving long-term local control. Adjuvant tamoxifen should be considered for all high-risk node-negative and all node-positive patients regardless of receptor status. Adjuvant chemotherapy is reasonable for high-risk node-negative and node-positive patients in good health and with reasonable life expectancy (>5 years), although clinical trials have not established efficacy for women in this age group. Older women with metastatic breast cancer are good candidates for endocrine therapy. Chemotherapy should be offered to those with progressive disease after endocrine therapy. There are inadequate numbers of older women enrolled in breast cancer clinical trials. Both physicians and patients should explore and define the barriers to clinical trial participation and develop successful interventions to overcome them.
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PMID:Breast cancer in older women. 861 51

Hormonal agents play a critical role in the palliation of advanced breast cancer, as well as adjuvant therapy to surgery and radiation in patients with primary breast cancer. Tamoxifen appears to be the therapy of choice for the initial treatment of metastatic breast cancer in both premenopausal and postmenopausal women, although some clinicians prefer oophorectomy or the use of luteinizing hormone releasing hormone analogues in premenopausal patients. Historically, second-line hormonal therapy for metastatic disease has been with a progestin; however, due to the troubling side effects of weight gain and dyspnea, progestins may soon be replaced by aromatase inhibitors. The development of new antiestrogens lacking estrogen-agonist activity for metastatic disease is in its earliest clinical developmental phases. For adjuvant therapy in postmenopausal women, there is conflicting evidence as to whether the combination of a hormonal agent (ie, tamoxifen) plus chemotherapy provides an advantage over hormonal therapy alone. In premenopausal women areas of active investigation include combination hormonal therapy (eg, tamoxifen plus luteinizing hormone releasing hormone analogues or oophorectomy) and combination chemohormonal therapy (concomitant v sequential). Tamoxifen had been associated with rare cases of thromboembolic events and secondary endometrial cancers. The etiology of these secondary cancers is unclear and controversial; however, the benefits of tamoxifen far outweigh the risks for both palliative and surgical adjuvant therapy. The success of tamoxifen in preventing cancer recurrence in the contralateral breast has led to clinical investigation of the drug for the chemoprevention of breast cancer in women at high risk for development of the disease. The role of tamoxifen for this indication remains to be determined following completion of the National Surgical Adjuvant Breast and Bowel Project trial in North America and additional trials in the United Kingdom and Italy.
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PMID:Hormonal approaches to breast cancer treatment and prevention: an overview. 882 59

Tamoxifen is a synthetic antiestrogen with both agonist and antagonist properties. It is believed to act primarily through binding to estrogen receptors in breast cancer cells, acting as a competitive inhibitor of estrogen. Tamoxifen has a wide range of systemic effects, possibly acting on every estrogen target tissue in the body. Tamoxifen therapy is associated with a significant reduction in the risk of recurrence and death in postmenopausal women with early stage breast cancer. In addition, it has been shown to effectively suppress preclinical breast cancer, as evidenced by the decrease in second primary breast cancers in adjuvant trials. Tamoxifen is also the most widely used endocrine therapy for women with metastatic breast cancer. Tamoxifen, acting predominantly as an estrogen agonist in the liver, has generally favourable effects on serum lipids in postmenopausal women. In addition, tamoxifen has been shown to preserve bone mineral density and may even decrease the risk of osteoporosis in these women. Most patients treated with tamoxifen have minimal adverse effects. Vasomotor symptoms are the most commonly reported events. Less frequently, vaginal discharge or dryness, nausea and depression have been reported. A slight increase in thromboembolic events in postmenopausal women taking tamoxifen has been suggested in some adjuvant trials. Rarely, ocular toxicity and hepatotoxicity are found. The adverse effect of primary importance is the increased incidence of endometrial carcinoma. Several studies indicate that almost all of the tumours are of low histological grade and stage, similar to those seen with exogenous estrogen use. The relative risk of endometrial cancer in women taking tamoxifen is about 2 to 4 times higher than for postmenopausal women not taking tamoxifen. The benefits of tamoxifen outweigh the risks in almost all postmenopausal women with estrogen receptor-positive early stage breast cancer and in all women with metastatic breast cancer. Should tamoxifen prove to be an effective chemopreventive agent for breast cancer, the risks and benefits of treatment will have to be more carefully assessed for this setting.
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PMID:Tamoxifen in postmenopausal women a safety perspective. 893 95

Tamoxifen is a widely used, effective, and well-tolerated agent in the treatment of primary and recurrent breast cancer. In the adjuvant setting, tamoxifen decreases the annual odds of recurrence and death by 25% and 16%, respectively. The toxicities of tamoxifen are of minor concern in the poor-prognosis group of women with metastatic breast cancer. In the more favorable group of women with early breast cancer, the benefits of tamoxifen appear to substantially outweigh the known toxicities. In retrospective analysis, tamoxifen has been consistently demonstrated to decrease the occurrence of contralateral second breast cancer and to be associated with an increased frequency of diagnosis of endometrial carcinoma. It is not known whether tamoxifen is promoting the growth of pre-existing, clinically occult endometrial carcinomas or is truly etiologic for the development of new cancers. The endometrial carcinomas that are associated with tamoxifen appear to have a biology and natural history similar to non-tamoxifen-associated endometrial carcinomas. There is no evidence supporting an association between hepatocellular carcinomas and tamoxifen in humans. Retrospective analysis of the association of colorectal carcinoma and gastric carcinoma provides little convincing evidence of a causal relationship, although further study is warranted.
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PMID:Scientific review of tamoxifen. Overview from a medical oncologist. 904 12

Breast cancer treatment has evolved greatly within the last 25 years. Tamoxifen was first introduced for the treatment of metastatic breast cancer in the 1970s and later became accepted as standard adjuvant therapy. The emergence of tamoxifen as first-line hormonal therapy for metastatic disease and in the adjuvant setting occurred due to its efficacy in achieving prolonged overall survival as well as improved disease-free survival, the latter of which improves the psychological and physical quality of life of the patient. Tamoxifen is currently being studied for the prevention of breast cancer. Completion of this important trial is eagerly awaited.
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PMID:Tamoxifen's impact on the management of breast cancer: the oncologist's perspective. 906 28

Tamoxifen (TAM) is widely used as therapy in early breast cancer and first-line endocrine therapy in metastatic disease. Despite this therapy, many patients relapse and an important question is: What is the preferred sequence of endocrine therapies in metastatic breast cancer (MBC). While treatment with oophorectomy, aminoglutethimide or progestins have been a logical choice after failure to Tamoxifen recent research has extended the options for endocrine therapy of MBC. New selective aromatase inhibitors (AI) are now in clinical use. The first commercially available of these inhibitors is LENTARON. The active ingredient of LENTARON is a steroidal compound 4-OH-androstenedione: Formestane. It is presented as a depot formulation and applied as an i.m. injection of 250 mg every second week. Previous findings from phase II trials have indicated similar activity as other endocrine treatment modalities. Clinical investigations in properly conducted phase III trials have revealed that the efficacy of LENTARON matches the results which can be obtained with TAM and Megace in trials of first and second-line endocrine therapy. Fifty-four and 51% of MBC patients, respectively, did benefit from therapy with LENTARON in these phase III trials by achieving objective responses or stable disease. Moreover, similar overall survival was seen. The systemic tolerability of LENTARON is comparable to that of TAM, and LENTARON seems less systemically toxic than Megace. Local side effects occured in approximately 7% of the patients giving rise mainly to pain or inflammation at the injection site. In elderly patients, LENTARON therapy assures compliance and no interference with other oral medications has been observed. In conclusion, since the endocrine treatment modalities are comparable in terms of efficacy the optimal sequence of these treatments is based upon differences in tolerability. Patients previously treated with Tamoxifen and with a high probability of a further endocrine response could preferably be treated with a selective AI like LENTARON as second-line endocrine therapy followed by a progestin upon progression in responders.
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PMID:Proper sequence of endocrine therapies in advanced breast cancer. 914 64

The role of anastrozole, a new selective aromatase inhibitor, in treating hormone-responsive metastatic breast cancer is discussed. Treatment options for hormone-dependent breast cancer focus on interfering with the endocrine system in an attempt to modify the effects of estrogen. Tamoxifen is the drug of choice for primary endocrine therapy, but there is a need for agents with similar or greater efficacy and better tolerability. Anastrozole inhibits the conversion of androgens to estrogens by aromatase. Bioavailability studies have demonstrated almost complete absorption of anastrozole after oral administration. The drug's terminal half-life after multiple doses is 50 hours. Anastrozole is cleared principally by the liver. Clinical trials comparing anastrozole with megestrol acetate demonstrated no significant differences in clinical efficacy, although a follow-up study revealed a longer median overall survival rate in patients receiving anastrozole. The drug is well tolerated. Among the most frequently reported adverse effects are asthenia, hot flashes, headache, and back pain. The recommended dosage is 1 mg daily. The average wholesale cost of month's supply of anastrozole is $187.20, compared with approximately $100 for generic megestrol acetate or aminoglutethimide plus hydrocortisone. Although anastrozole will likely become the preferred second-line agent in the treatment of postmenopausal breast cancer in patients with disease progression after tamoxifen therapy, it is not a therapeutic alternative to aminoglutethimide on the basis of approved indications. Anastrozole and other aromatase inhibitors may have multiple applications in treating hormone-responsive breast cancer.
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PMID:Anastrozole: a selective aromatase inhibitor for the treatment of breast cancer. 952 27


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