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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of 17 beta-estradiol versus tamoxifen on the growth and metabolism of MCF7 human breast cancer cells, in culture and in tumors implanted in nude mice, were studied by 31P and 13C nuclear magnetic resonance spectroscopy and by proton magnetic resonance imaging. In culture, the content of the phosphate metabolites including nucleoside triphosphates (NTP), phosphomonoesters, phosphodiesters and inorganic phosphate (Pi) were not affected by tamoxifen treatment. However, in the presence of estrogen the rate of glucose consumption and lactate production via glycolysis (270 and 280 fmol/cell.h, respectively) were twice that of tamoxifen treated cells. Estrogen rescue of tamoxifen treated cells indicated that glycolysis induction occurs at the early stages of the hormonal response. The in vivo studies included recording of proton images that provided an accurate measure of tumor size and distribution of tumor cells, necrotic regions and stromal tissue. Tamoxifen caused enhanced necrosis extending from the center of the tumor during the first two days of treatment (12 h to 6 days). This was followed by growth of reparative tissue along with tumor regression. Tamoxifen also modified the content of the phosphate metabolites, increasing markedly (P less than 0.0002) the ratio of NTP to Pi from 0.41 before treatment to 1.75 9-19 days after treatment. This change was attributed to the enhanced growth of repair tissue. The results provide new information regarding the response of human breast cancer to hormonal treatment and suggest a mechanism for the induction of tumor regression by tamoxifen.
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PMID:Tamoxifen induced changes in MCF7 human breast cancer: in vitro and in vivo studies using nuclear magnetic resonance spectroscopy and imaging. 152 59

Tamoxifen, an antiestrogen commonly used in breast cancer therapy, potentiated the lethality of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) when coadministered to female CD1 mice, despite the virtual lack of toxicity associated with the administration of tamoxifen alone. The 58-day ip LD50 of TCDD was reduced from 330 to 185 micrograms/kg by sc administration of 1 mg/kg/day tamoxifen. A significant dose-response relationship was observed for the potentiating effect of tamoxifen on TCDD lethality. All mice receiving TCDD developed a centrilobular pattern of hepatocellular degeneration and necrosis with perivascular infiltration of inflammatory cells. Clinical chemistry parameters were indicative of liver disease. Abnormalities in mice receiving tamoxifen plus TCDD were similar to, but more severe than, those in mice receiving TCDD only. Seven days after administration of [14C]TCDD, liver retention of radioactivity was increased 80-100% by coadministration of tamoxifen. This elevated retention was associated with a 50 and 37% decrease in excretion of radioactivity by the urinary and fecal routes, respectively. Our results suggest that the potentiation of TCDD toxicity by tamoxifen is associated with decreased excretion of TCDD, leading to elevated liver retention and enhanced severity of liver pathology.
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PMID:The potentiation of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity by tamoxifen in female CD1 mice. 152 43

Tamoxifen is a nonsteroidal antiestrogen that has found successful applications for each stage of breast cancer in the treatment of selected patients. Tamoxifen was originally introduced for the treatment of advanced disease in postmenopausal women; however, the drug is now also available for the palliative treatment of premenopausal women with estrogen receptor (ER) positive disease. The proven efficacy of tamoxifen and the low incidence of side effects made the drug an ideal agent to test as an adjuvant therapy for women with node-positive breast cancer. Laboratory studies indicate that long-term treatment schedules may provide maximal benefit in preventing recurrence, and recent analysis of clinical trials demonstrates that between 2 and 5 years of adjuvant tamoxifen therapy provides a survival advantage for postmenopausal women with node-positive disease. Similarly, adjuvant studies in node-negative breast cancer have demonstrated an increase in the disease-free survival of both pre- and postmenopausal patients with ER-positive tumors. However, the extended use of tamoxifen has raised questions about the long-term safety of antiestrogen therapy. Of special concern is the impact of tamoxifen on ovarian function in premenopausal women and the potential risks to the fetus if pregnancy occurs. Fortunately, there are no reports about the teratogenicity of tamoxifen in the human, but it is important that physicians counsel women about the risk of pregnancy. Tamoxifen should not be used if a patient is pregnant. Initial concerns that the long-term administration of an antiestrogen would increase bone loss and increase the risks of coronary heart disease appear to be unwarranted. Tamoxifen has some estrogen-like activities in postmenopausal women and causes a preservation of bone in the lumbar spine and a decrease in circulating cholesterol. Indeed, a reduction in fatal myocardial infarction (MI) has been noted during 5 years of tamoxifen therapy, possibly the direct result of a prolonged reduction in circulating cholesterol. However, the estrogen-like qualities of tamoxifen that could be valuable as a hormone replacement therapy for all postmenopausal women following a diagnosis of breast cancer may also increase the risk for developing endometrial carcinoma. To date, there are only a few reports of endometrial carcinoma being diagnosed during adjuvant therapy with tamoxifen; however, any instances of uterine bleeding or spotting should be followed up with an endometrial biopsy. There are some concerns about large doses of tamoxifen promoting liver cancer in rats. These results are of particular concern if tamoxifen is to be used as a preventive in normal women.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of tamoxifen in the treatment and prevention of breast cancer. 158 40

504 evaluable node positive oestrogen receptor (ER) positive breast cancer patients were randomly allocated to receive either 5 years tamoxifen treatment or chemotherapy [six courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 4 courses of epirubicin] or a combination of both treatments. At a median follow-up of 5 years tamoxifen appeared to be more effective than chemotherapy, the difference being highly significant in postmenopausal women. The addition of chemotherapy to tamoxifen was not able to significantly improve the results achieved by tamoxifen alone, irrespective of menopausal status. Trends were similar even after stratification for the number of involved nodes. The protective effect of tamoxifen in terms of reduction of the odds of death increased with time and no rebound phenomena on recurrence or death has occurred so far after the completion of tamoxifen treatment. Overall, the prognostic value of number of involved nodes and of progesterone receptor (PgR) status was confirmed by multivariate analysis. However, the predictive value of PgR was lost in patients receiving tamoxifen alone. Similarly, the degree of ER positivity was not predictive of the response to tamoxifen. Tamoxifen treatment should still be regarded as the gold standard for postmenopausal ER positive patients. In younger women the antioestrogen proved to be safe and at least as effective as chemotherapy. However, the analysis of the annual risks suggests that the concurrent or the sequential use of chemotherapy and tamoxifen might represent a more appropriate treatment for this patient subset, particularly for those with four or more involved nodes. Different cut-offs of ER and PgR assays from those we have arbitrarily employed in the present analysis should probably be used to select more properly the patients who can benefit from endocrine therapy.
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PMID:Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen-receptor positive breast cancer patients. An update at 7 years of the 1st GROCTA (Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group) trial. 159 Oct 91

As part of a clinical trial of adjuvant endocrine treatment in postmenopausal women with operable breast cancer serial bone density measurements have been performed by dual photon absorptiometry. Tamoxifen alone was given to 26 women, and 20 received additional prednisolone. By 24 months after entry there was no significant difference between mean bone density of the two groups, nor any significant change from baseline levels. There was a mean gain of 0.46% in the tamoxifen group and 1.95% in those given additional prednisolone. Thus the predicted steroid-induced bone loss was inhibited by tamoxifen. This may be of more general use in prevention of osteoporosis in patients requiring long-term steroid treatment.
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PMID:Tamoxifen protects against steroid-induced bone loss. 159 Oct 93

Between 1979 and 1987, 170 patient with stages 0, I and II breast cancer were treated with breast conservation therapy. Twenty-eight women (16%) had intraductal carcinomas, 110 (65%) stage I disease and 32 (19%) had stage II breast cancers. Seventy-five percent of the patients received no adjuvant systemic treatment, whereas 20% received adjuvant chemotherapy and 5% were given Tamoxifen. All patients received radiation therapy to the breast after lumpectomy and, when appropriate, axillary dissection. Twelve patients (7%) recurred within the treated breast, whereas two patients (1%) recurred in regional lymph nodes. Fourteen women (8%) developed distant metastases and seven women (4%) developed contralateral breast cancer. The actuarial 5 year disease-free survival was 92% for the patients with intraductal carcinoma, 90% for T1 and 65% for T2 patients. Overall actuarial survival was 100%, 96% and 87%, respectively. The St. Luke's Hospital results are comparable to those reported in the literature. We conclude that breast conservation therapy, including irradiation, is an alternative to modified radical mastectomy and that this option should be thoroughly discussed with the patient.
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PMID:Breast conservation therapy. The St. Luke's Hospital experience. 159 2

Six to 12 cycles of CMF is regarded as the standard regimen for adjuvant chemotherapy for breast cancer, producing 10-20% increase in survival for premenopausal and node-positive patients. Tamoxifen combined with CMF has induced an additional reduction in recurrence rate only in postmenopausal patients. Oral administration of 5-FU or its derivatives combined with tamoxifen for as long as 1-2 years is the regimen most widely used in Japan for considerable improvement in survival. But it needs further evaluation in comparison with CMF, and in ultimate duration of treatment and better combination with other drugs. Adjuvant chemotherapy for node-negative patients is advocated in the U.S., where the recurrence rate is as high as 30%. Only 10% of Japanese n0 patients undergo recurrence. Therefore, adjuvant therapy should be given only to high-risk patients.
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PMID:[Adjuvant chemotherapy therapy of breast cancer]. 160 53

The human breast cancer cell line MCF-7 contains estrogen receptors and responds to estrogens with an increase in growth rate and to antiestrogens with a decrease in growth rate. Estrogen stimulation of cell proliferation is concomitant with an increase in the synthesis and secretion of three proteins with mol. wt 52 kDa, 61 kDa and 66 kDa and a decrease in the synthesis and secretion of a 42 kDa protein. The antiestrogen ICI 164,384 has a complete estrogen antagonistic effect on the synthesis of these secreted proteins, whereas the antiestrogen tamoxifen has an agonistic effect on the synthesis and secretion of the 52 kDa protein. We believe that the above mentioned estrogen regulated secreted proteins are either directly or indirectly involved in control of cell proliferation, and the less pronounced inhibitory effect of tamoxifen on cell proliferation compared to ICI 164,384 may be due to agonistic effects of tamoxifen. A tamoxifen resistant variant of the MCF-7 cell line, the AL-1 subline, can be growth inhibited by ICI 164,384, although a higher concentration is needed to inhibit the AL-1 cells compared to the parent MCF-7 cells. Tamoxifen has no effect on secreted proteins from the AL-1 cells, whereas ICI 164,384 has a complete estrogen antagonistic effect on secreted proteins, indicating that the mechanisms by which estrogens and antiestrogens influence cell proliferation may be via up and down regulation of secreted proteins with growth regulatory functions.
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PMID:Effect of estrogen and antiestrogens on cell proliferation and synthesis of secreted proteins in the human breast cancer cell line MCF-7 and a tamoxifen resistant variant subline, AL-1. 162 27

Over 2,000 patients with early breast cancer were recruited into a trial between 1980 and 1985. This trial was of a factorial 2 x 2 design to investigate the benefits of a short course of perioperative cyclophosphamide or tamoxifen 20 mg daily for 2 years. At the tenth year of follow-up no significant benefit is noted for perioperative cyclophosphamide, however the main effect analysis for adjuvant tamoxifen demonstrates a significant improvement in disease-free survival which increases with time during the follow-up period. These results are in keeping with the World Overview of Trials of Adjuvant Tamoxifen. However, this study is unique, having a large number of node negative patients and over 500 premenopausal women in a comparison of tamoxifen and control. The relative risk reductions for the node negative patients for disease-free survival are greater than for the node positive patients. This might suggest that the absolute benefit for adjuvant tamoxifen is similar in both groups of patients, bearing in mind the increased risk of relapse with the node positive patients. No trend for interaction emerges according to age or menopausal status suggesting an identical benefit for premenopausal women. Of particular interest is the development of contralateral breast cancer. The initial overall effect which emerged at the third year of follow-up ceases to be apparent. However, subgroup analysis according to menopausal status suggests a trend for interaction with a reduction in the risk of contralateral breast cancer in the postmenopausal women and an increase in the risk of contralateral breast cancer in premenopausal women. Plausible mechanisms exist to explain this difference in outcome and these data need to be checked against other large trials of adjuvant tamoxifen at a time when we are considering the chemoprophylaxis of breast cancer in high risk premenopausal women.
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PMID:Results of the Cancer Research Campaign Adjuvant Trial for Perioperative Cyclophosphamide and Long-Term Tamoxifen in Early Breast Cancer reported at the tenth year of follow-up. Cancer Research Campaign Breast Cancer Trials Group. 162 42

Tamoxifen is the most widely used non-steroidal antiestrogen compound for adjuvant treatment of postmenopausal breast cancer. Tamoxifen has both antiestrogen and estrogen-agonistic activity, which depends on the target tissue involved owing its systemic distribution. Upon the endometrium the agonistic estrogenic effect, so-called "paradoxical" effect, is suggested to induce proliferative changes such as hyperplasia or carcinoma. The authors report four cases of endometrial cancer developed in postmenopausal patients with breast cancer receiving tamoxifen. According to the literature data, the relationship of the tamoxifen to the endometrial remains uncertain: women with breast cancer are at increased risk for this neoplasm sharing common aetiologic hormonal factors and, in most published case reports, the uterine cavity has not been checked up before starting tamoxifen administration.
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PMID:[Cancer of the endometrium caused by antiestrogens]. 163 76


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