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

Blood tamoxifen levels were determined for patients with metastatic breast cancer following initial and chronic dosing at twice daily 10 mg/m2 or a 20 mg/m2 single dose. Median time to response was six weeks. Blood tamoxifen levels at that time were ten-fold greater than those obtained after an initial single dose; however, steady-state values were not achieved until 16 weeks of chronic dosing. On a loading dose schedule of 40 mg/m2 twice daily for seven days and 20 mg/m2 daily thereafter, blood levels greater than or equal to 10 mg/m2 twice daily steady-state values were reached in one week. Levels drawn at peak and trough times suggest that tamoxifen may be given on a once-daily basis. Tamoxifen half-life was 9-12 hours after the initial dose and seven days after chronic dosing.
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PMID:Clinical pharmacology of tamoxifen in patients with breast cancer: correlation with clinical data. 727 32

Tamoxifen blood levels were measured in patients with metastatic breast cancer after single-dose and continuous administration, using a traditional dose schedule of 10 mg/m2 twice daily, a single daily dose schedule of 20 mg/m2; and several loading dose schedules of 20-80 mg/m2 twice daily x 7 days, then a 20-mg/m2 single daily dose thereafter. Using the traditional 10-mg/m2 twice daily schedule, values after continuous administration at the time clinical responses were observed were greater than or equal to 10 x peak values observed after a single dose. Using a loading dose schedule of greater than or equal to 40 mg/m2 twice daily x 7 days, values known to be associated with a response were present by 3 hours, as opposed to greater than or equal to 7 days with the traditional schedule. Levels obtained at peak and trough times with the once-daily schedule suggest tamoxifen may safely be given on a once-daily basis, particularly after the first 8 weeks of therapy. Half-life of tamoxifen after continuous administration is prolonged, and levels obtained for up to 6 weeks after drug discontinuation suggest that false-negative cytoplasmic estrogen receptor (ER) determinations may be obtained if tissue for ER is sampled within 4-6 weeks of prolonged tamoxifen administration.
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PMID:Clinical pharmacology of tamoxifen in patients with breast cancer: comparison of traditional and loading dose schedules. 742 61

Tamoxifen was evaluated in a phase II trial as initial hormonal therapy in premenopausal patients with metastatic breast cancer. The study design was such that responders remained on tamoxifen therapy; those who initially or subsequently progressed went on to ovarian ablation either by surgery or irradiation. Of 42 evaluable patients treated with tamoxifen, three had complete responses (CR), ten had partial responses (PR), and four remained stable (ST), giving total response rates of 32% (CR + PR) or 41% (CR + PR + ST). Among the 18 patients with positive estrogen (ER) or progesterone (PgR) receptors, there were eight responders, but only one responder (ST) in the nine patients with negative ER or PgR. Of the 25 patients who failed to respond to tamoxifen, 13 underwent ovarian ablation; all failed to respond. These 13 included four patients who were ER positive or equivocal and PgR positive or unknown. Nine tamoxifen responders (CR + PR + ST) have subsequently progressed; of these, eight have gone on to ovarian ablation. Six of these eight have responded (five PR and one ST) to ovarian ablation, and one has failed to respond. Thus, steroid receptors generally predicted a patient's response to tamoxifen therapy, but response to tamoxifen also strongly predicted a patient's subsequent response to ovarian ablation.
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PMID:Tamoxifen therapy in premenopausal patients with metastatic breast cancer. 742 62

Both chemotherapy and hormonal therapy have been used in the adjuvant therapy of breast cancer to treat micrometastatic disease before it is clinically detectable. Several prospective, randomized trials consistently have demonstrated that disease-free survival can be significantly prolonged by the use of adjuvant chemotherapy. In some of these trials overall survival was increased as well. Premenopausal nodal-positive patients should receive adjuvant chemotherapy e.g. six cycles of CMF. Tamoxifen reduces overall tumor recurrence and mortality in postmenopausal estrogen receptor positive patients and to a lesser extent in estrogen receptor poor or negative patients. The effect of GnRh-analog for premenopausal patients with is currently investigated in multicentric studies. A response related strategy for management of metastatic breast cancer by hormonal manipulation and cytotoxic chemotherapy is outlined.
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PMID:[Chemotherapy and hormone therapy in breast carcinoma]. 770 19

Tamoxifen and megestrol acetate are used as a hormonal treatment for metastatic breast carcinoma. It is suggested that the use of tamoxifen may induce endometrial cancer. In this article we describe nine patients under hormonal treatment for metastatic breast cancer with, firstly, tamoxifen and, later, megestrol acetate. These nine patients all had symptoms of postmenopausal vaginal blood loss during therapy with megestrol acetate, an indication to perform a diagnostic dilatation and curettage. By histopathological examination the curettings showed a decidualized stroma with an infiltration of lymphocytes, some plasma cells and many eosinophils. In none of the patients was atypical hyperplasia or malignancy found. The dilatation and curettage had also a therapeutic effect, since only one of the patients still had complaints, while the other eight did not complain of postmenopausal bleeding again. We review the literature and discuss the value of a diagnostic dilatation and curettage.
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PMID:Results of curettage for postmenopausal vaginal bleeding in women treated with tamoxifen and megestrol acetate for progressive metastatic breast carcinoma. 782 89

Tamoxifen is actually considered the drug of choice for the hormonal treatment of early and metastatic breast cancer due to its efficacy and low toxicity. In addition, clinical trials of adjuvant therapy have demonstrated a 35% decrease in controlateral breast cancer in women receiving tamoxifen compared with controls, suggesting a potential role for this drug in chemoprevention of breast cancer in healthy women at increased risk of disease. Although tamoxifen is usually classified as an estrogen antagonist it also has partial estrogenic effects in some tissues such as liver, bone and uterus. The estrogenic action of tamoxifen on lipid metabolism and bone mineral density suggests additional benefits in protection against cardiovascular diseases and osteoporosis in postmenopausal women. Of particular interest could be the use of tamoxifen as an alternative to traditional estrogen replacement therapy in postmenopausal women previously treated for breast cancer or at increased risk of disease due to family history or histology on breast biopsy. The potential adverse effects of tamoxifen are partially similar to those of ERT and includes an increased risk of endometrial cancer, hepatic diseases, thromboembolic alterations and ocular toxicity. The mechanism of action of tamoxifen is briefly examined and the potential toxic effects and benefits of tamoxifen treatment are discussed.
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PMID:Metabolic effects of tamoxifen in postmenopause. 784 May 29

Hormonal therapy for breast cancer began more than a century ago with the observation that bilateral oophorectomy caused tumor regression in selected premenopausal patients. In the first half of this century, besides extending ablation of ovarian function to photon irradiation, surgical adrenalectomy and hyophysectomy were introduced, and hormonal additive therapy was established. Regression rates for advanced breast cancer with all types of endocrine therapy at this point did not exceed 35%. The demonstration that adjuvant systemic therapy can prolong the disease-free interval and improve overall survival has been a major advance in the management of breast cancer, the rationale was to control or eliminate micrometastases before tumor recurrence. The nonsteroidal antiestrogen tamoxifen was chosen for the majority of studies since the mid-1970s. Since the first report of successful treatment of metastatic breast cancer, the number of treated women worldwide has reached over 3,000,000. Objective response rate (CR+PR following UICC) in unselected patients is 34%. Tamoxifen has been used successfully to treat both pre- and postmenopausal women with all stages of the disease. In an overview analysis of 30,000 patients from 40 trials of adjuvant tamoxifen, a significant increase was found in both disease-free and overall survival. When patients were separated by nodal status, statistically significant increases were observed in disease-free and overall survival for both node-positive and node-negative patients. Women over 50 appear to benefit most from tamoxifen treatment experiencing highly significant increases in disease-free and overall survival regardless of nodal status. However, since tamoxifen primarily acts as a cytostatic and not cytotoxic agent, most patients ultimately experience disease recurrence or progression during or after therapy. Newer antiestrogens include trioxifene, toremifene, and droloxifene (3-OH-tamoxifen). Randomized, prospective studies are still under way to establish their clinical superiority (or lack of it). Progestins exert direct antiproliferative effects on human breast cancer cell lines. They may also exert direct antiestrogenic action by increasing the oxidative activity of 17 beta-hydroxy-steroid-dehydrogenase, thereby facilitating the conversion of estradiol to estrone. Progestins may exert additional antiestrogenic effects by suppressing estrogen receptor levels. As they also cause estrogen deprivation indirectly through suppression of pituitary ACTH secretion, resulting in reduced production of adrenal androgen precursors, both low- and high-dose regimens have been studied. Aromatase inhibition in premenopausal women interrupts estrogen biosynthesis; the reflex rise in FSH then stimulates production of new aromatase enzyme, and the LH increment results in enhanced ovarian steroidogenesis, counteracting the inhibitory action of aromatase-blocking drugs on the ovary.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine management of breast cancer. 787 88

Since its introduction in the early seventies, the list of indications for the use of the antiestrogen tamoxifen has been continuously expanded. Tamoxifen is now used for the treatment of metastatic breast cancer and for long-term and often indefinite administration as an adjuvant therapy. Large clinical trials in three countries are now evaluating the efficacy of tamoxifen as a preventive agent. However, tamoxifen therapy has been associated with an increased incidence of endometrial carcinoma. Laboratory and clinical data available to date on this controversial issue can be summarized as follows: a) Tamoxifen can have an estrogenic effect on endometrium in the presence of low estrogen levels. b) Tamoxifen treatment is probably associated with an increased incidence of endometrial cancer; however, this association appears to be linked to higher tamoxifen doses (40 mg/d). d) It is not known whether tamoxifen causes or allows the identification of occult endometrial carcinoma. e) At the present time there is evidence for a tumor promoting effect of tamoxifen on endometrial cancer at a dose of 20 mg per day. f) Replacement of tamoxifen by 'pure' antiestrogens or coadministration of progestins with tamoxifen do not appear to offer benefit unless clinical trials demonstrate a reduced incidence of endometrial problems. g) Patients must be evaluated for pre-existing endometrical carcinoma before starting tamoxifen therapy. f) Close followup of long-term tamoxifen patients with endometrial biopsies is recommended with individuals who experience symptoms.
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PMID:What do we know and what don't we know about tamoxifen in the human uterus. 798 54

The management of breast cancer in older women is a major challenge. A meta-analysis of randomized trials of adjuvant therapy in early stage breast cancer has indicated that the use of the antiestrogen tamoxifen improves relapse-free and overall survival for postmenopausal women, including those older than age 70 years. Tamoxifen therapy is of greatest benefit in patients whose primary lesions are estrogen- and progesterone-receptor positive, but lesser yet still significant benefits are seen in receptor-negative patients. Adjuvant chemotherapy has only been minimally studied in older women, because earlier trials tended to exclude women older than age 70 years from protocol entry. Trials are needed to explore the role of adjuvant chemotherapy in older women, especially those older than age 70 years. Metastatic breast cancer is incurable. Standard endocrine and chemotherapy regimens may be of great palliative benefit but probably only have modest effects on prolonging survival; older women should be offered such treatment. Initiating treatment for metastases with endocrine therapy does not compromise survival, even when such therapy is given to women who have receptor-negative malignancy. Patients progressing on endocrine therapy or whose metastatic disease is life-threatening should be considered for chemotherapy. Older women in generally good health tolerate standard doses of chemotherapy as well as their younger counterparts. Future research in this setting should include clinical trials designed specifically for the elderly and should include quality-of-life assessment as a major end point.
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PMID:The role of chemotherapy and adjuvant therapy in the management of breast cancer in older women. 808 84

Tamoxifen (Nolvadex) has been in use for over 20 years and currently is probably the most prescribed anti-cancer medication in the world. It is an orally effective, synthetic, non-steroidal, estrogen antagonist and agonist agent. In studies and trials it has been shown to have only limited side effects. It has produced regressions in women with fibrocystic changes, including precancerous ones, and in those with metastatic breast cancer, where its benefits were first observed. It has increased disease free survival (DFS) and overall survival (OS) rates when given as an adjuvant systemic type of therapy in women with early breast cancers, and it has reduced the incidence of contralateral breast cancers. In addition there are reports indicating its long term use, especially in postmenopausal women, may produce overall health benefits. Over the years an increasing body of data has emerged allowing for viable hypotheses about the possible use of tamoxifen in the prophylaxis of breast cancer, namely that when administered in long-term therapy it may reduce the incidence of breast cancer in women so treated, that it may provide overall health benefits, particularly in postmenopausal women, and that its benefits should far outweigh any risks from its relatively limited side effects. However, carefully designed and conducted clinical trials are needed to test the safety of tamoxifen and its ability to prevent breast cancer before it is advocated for the prophylactic treatment of healthy women to prevent breast cancer, even realizing the increasing magnitude of the breast cancer problem.
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PMID:The role of tamoxifen in the prevention and treatment of benign and malignant breast lesions: a chemopreventive. 835 20


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