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

Cytoplasmic estrogen receptor (ERC), nuclear estrogen receptor (ERN), and cytoplasmic progesterone receptor (PRC) were studied in 217 human breast cancers. ERC was found in 48.4%, ERN in 37.8%, and PRC in 32.7%. Histological grade was significantly correlated with ERC, ERN and PRC. Well-differentiated tumors were more frequently positive for the receptors while poorly differentiated tumors were generally negative for the receptors. Seventy one percent of the most differentiated tumors were ERC(+) ERN(+) PRC(+) and ERC(+) ERN(+) PRC(-). The histological grading system consists of tubule formation, nuclear pleomorphism and mitotic activity. There were significant correlations of receptor contents with nuclear pleomorphism and more mitotic activity. This was also confirmed by the study on the relationships between receptor contents and thymidine labeling index or mitotic index. The possibilities of receptors decreased with an increase in nuclear diameter. And there was a significant correlation between the receptor contents and the numbers of intracellular organellas in ultrastructural features of breast cancer cells. Among 33 cases of advanced or metastatic breast cancer submitted to endocrine therapy, 13 cases showed clinical response (CR or PR) These cases were both ERC and ERN positive independently of PRC status. Therefore, it is suggested that hormone receptor may be used as an independent prognostic factor in breast cancer.
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PMID:[Estrogen receptor in human breast cancer: relationship between the receptor contents and the histological and cytomorphological characteristics]. 649 99

The antiestrogenic agent tamoxifen was evaluated in 17 pre- and 103 postmenopausal women with recurrent or metastatic breast cancer at two dose levels (2 and 3 x 10 mg daily). Dose-related differences in the results were not observed. Altogether 49.2% of these patients responded to therapy (10% complete remissions, 9.2% partial remissions, 30% no change). While a response rate of 52.5% was found in the postmenopausal group, the rate was markedly worse in premenopausal women (29.4%). In postmenopausal patients there was a poorer remission rate in older women. Regarding the dominant site of lesions, the best results were achieved in patients with lung and pleural metastases, followed by soft tissue metastases. Patients with a disease-free interval of more than 100 months responded better to therapy than those with a shorter interval. Long-term results were much more favorable in patients who primarily responded to tamoxifen than in nonresponders. As the most valuable prognostic criterion, the hormone receptors were assayed. 75% of the estrogen receptor (ER) and progesterone receptor (PgR) positive and 55,6% of the ER-positive and PgR-negative patients derived benefit from this treatment in contrast to only 19% of the ER- and PgR-negative women. Plasma levels of estradiol, progesterone, testosterone, and FSH were not changed by tamoxifen, but average cortisol and prolactin concentrations were altered significantly. A short-time increase of the prolactin level 2 weeks after onset of tamoxifen treatment and a decrease thereafter also seem to be good prognostic signs. Side effects were few and did not occur more severely or frequently in the higher dose group.
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PMID:[The antiestrogen tamoxifen in advanced breast cancer (author's transl)]. 677 66

Recent insight into the mechanism of steroid hormone receptors in human breast cancer has led to new approaches in treatment strategy. Estrogen receptor (ER) has now replaced clinical criteria in the selection of patients for endocrine therapy. Patients whose tumors do not contain ER should not be subjected to hormonal manipulation. In addition, ER measured on the primary tumor has been found to be an independent prognostic factor for both recurrence and survival. Patients with ER negative primary tumors have a poorer prognosis. This information may be useful in the design and selection of therapy for future adjuvant clinical trials. In metastatic breast cancer, the absolute ER value may provide valuable information regarding endocrine responsiveness. In addition, the measurement of progesterone receptor (PgR) may provide additional insight for predicting with confidence those patients likely to respond.
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PMID:Steroid hormone receptors in the management of human breast cancer. 701 82

This report summarizes some of the clinical correlations of cytosol estrogen receptor (RE) and progesterone receptor (RP) measurement and presents methods of improving the accuracy of receptor assays in selection of patients for endocrine treatment of breast cancer. Clinical data from 99 metastatic breast cancer patients were reviewed. Patients with RE positive tumors had a significantly greater response rate overall to endocrine therapy than those with estrogen negative tumors. The difference between the RE positive and RE negative groups was significant whether or not patients with static disease were included in the remission category. 2 of 3 RE negative patients who responded to endocrine treatment were premenopausal. In 57 treatments in which both RE and RP measurements were available, RP assay did not improve the discrimination between responding and nonresponding patient groups. In particular, the response rate in the RE positive groups was equally divided between those tumors which were RP positive and RP negative. Tumor RE concentration also had an influence on tumor responsiveness; when the level of RE was 100 fmol/mg, all tumors responded to hormonal treatment, whereas the response rate in tumors with RE 50 fmol/mg was significantly greater than in tumors of RE content between 5 and 50 fmol/mg (P .05). Retrospective analysis of the disease-free interval for a patient group in remission showed that RE positive patients had significantly longer disease-free interval (37+ or -28 months) than RE negative patients (22.7+ or -20 months) (P .002).
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PMID:Clinical applications of receptor measurements in breast cancer. 736 74

Mifepristone is a potent oral antiprogestogen which acts at the level of the receptor, having a high affinity for the progesterone receptor. Most of the clinical trials have studied its efficacy in the termination of early pregnancy when used in conjunction with a low dosage of a prostaglandin analogue. In these studies, mifepristone 100 to 600mg administered as a single dose or over 3 or 4 days, 36 to 48 hours before a prostaglandin analogue given vaginally, intramuscularly or orally, induced complete abortion in about 95% of women. Used alone, mifepristone is an effective cervical priming agent prior to termination of first trimester pregnancy by vacuum aspiration, and facilitates termination of second trimester pregnancy by prostaglandin by reducing the interval between the start of prostaglandin treatment and termination, the cumulative prostaglandin dosage, and the adverse effects associated with these drugs. Mifepristone can also be used to induce labour in cases of intrauterine fetal death. Mifepristone has been shown to be an effective postcoital contraceptive with a likely emergency role, since its repeated use modifies the menstrual cycle. Pilot studies have been performed in unresectable meningioma and metastatic breast cancer, and in Cushing's syndrome. Mifepristone is generally well tolerated, and thus is an effective, appropriate, medical alternative to surgical termination of early pregnancy. It has as yet unexplored potential as a postcoital contraceptive and in oncology.
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PMID:Mifepristone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. 768 9

Systemic treatment almost certainly prolongs the median survival of women with metastatic breast cancer, and it may prolong the survival of a small number of patients substantially. Even with conventional therapy, 10% or more patients may live into the second decade after recurrence. However, the disease cannot be eradicated, and the primary goal of treatment remains palliation and improvement of the quality of life. Because of the great variability in the pattern and course of the disease from one patient to another, therapy should be selected judiciously to maximize response and minimize toxicity. In some clinical situations, such as pathologic fractures and brain metastases, local therapies alone, such as surgery or irradiation, are the treatments of choice. Patients who will respond to endocrine therapy are well defined, and all patients with the characteristics of an endocrine responder deserve a chance at palliation with this modality alone because of its limited toxicity. A number of new forms of endocrine therapy with more specific targets at estrogen and progesterone receptor sites are now in clinical trials. When used appropriately, chemotherapy significantly improves patient quality of life despite its toxicity. No drug combinations, schedules, or doses have been shown to prolong survival or provide better net palliation than classic CMF (oral cyclophosphamide with intravenous methotrexate and 5-fluorouracil) or CAF (intravenous cyclophosphamide, doxorubicin, and 5-fluorouracil). Treatment with these combinations in excess of 6 to 9 months provides only marginal additional benefits and no survival advantage. The role of high dose chemotherapy with autologous bone marrow transplantation remains a promising area of investigation, but the available survival data are entirely compatible with the possibility that this modality will eventually prove inferior to conventional therapy. Many new cytotoxic agents with unique mechanisms of action are currently under investigation, including taxol, taxotere, Topotecan, and amonafide. Taxol may be the most promising therapy now available for patients whose disease has become refractory to doxorubicin. Biologic therapies using monoclonal antibodies against a specific oncogene or its product have entered clinical trials, and novel drug delivery systems using liposomes are under evaluation.
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PMID:Management of metastatic breast cancer. 791 Sep 93

Expression of the hormone-regulated genes, pS2, prolactin-inducible protein (PIP) and fatty acid synthetase (FAS), was investigated by Northern blotting in primary breast carcinoma, metastatic breast cancer in axillary lymph nodes, in uninvolved breast tissue from mastectomies and in normal lymph nodes. There were considerable differences in expression of the genes between the tissues. The proportion of tissues containing PIP-mRNA decreased from uninvolved breast tissue to primary breast carcinoma to metastatic carcinoma. The reverse applied to FAS-mRNA which was found more often in metastatic cancer than in primary cancer, and least frequently in uninvolved breast tissue. Yet another pattern was observed for pS2 expression. The highest proportion of tissues demonstrating gene expression was found in primary breast cancer with both metastatic tumor and uninvolved breast tissue expressing the gene less frequently. pS2-mRNA and PIP-mRNA could only rarely be detected in trace amounts in normal lymph nodes. In contrast, FAS-mRNA was present in about one third of normal lymph nodes. Only pS2-mRNA showed an association with estrogen and progesterone receptor status.
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PMID:Hormone-regulated genes (pS2, PIP, FAS) in breast cancer and nontumoral mammary tissue. 794 16

Antiprogestins form a new potential treatment modality for breast cancer and their mode of action has been assessed in vitro on several breast cancer cell lines, in vivo in rats with dimethylbenzanthracene (DMBA)-induced mammary tumours and in vivo in patients with metastatic breast cancer. In vitro in serum-free medium, the progestin Org 2058 and antiprogestins RU486 and Org 31710 caused a dose-dependently stimulated MCF7 cell growth. Both antiprogestins dose-dependently inhibited the oestrogen-stimulated proliferation of progesterone receptor (PgR)-rich T-47D cells in DCC medium. Inhibition by Org 31710 plateaued at 10(-8) M (74% inhibition), compared with RU486 at up to 10(-6) M (53% inhibition). No inhibition was observed at doses of 10(-12)-10(-6) M of both antiprogestins in the absence of oestradiol. The proliferation of the ZR-75.1 and MDA-MB-231 cell lines was not or only marginally affected by either antiprogestin. Rats with DMBA-induced mammary tumours given prophylactic treatment with RU486 displayed a doubled latency period. Antiprogestins were slightly more effective than tamoxifen or progestins in rats with existing tumours. Org 31710 sometimes showed a somewhat more pronounced inhibitory effect than the antiprogestins Org 31806 and RU486. Combined antiprogestational and anti-oestrogenic treatment showed striking additive growth inhibitory effects resulting in clear tumour remissions, in the presence of very strong suppression of oestrogen and PgRs. The growth inhibitory effect of luteinizing hormone-releasing hormone agonists was potentiated by antiprogestins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pre-clinical and clinical treatment of breast cancer with antiprogestins. 796 63

Membrane-associated phospholipase A2 (M-PLA2) is an enzyme that hydrolyses the sn-2 fatty acyl ester bond of phosphoglycerides. We measured M-PLA2 concentration in tissue extracts from 325 human breast cancers using a specific radioimmunoassay recently developed. Correlation analyses between the tissue concentration of M-PLA2 and clinicopathological factors showed that the enzyme level was significantly higher in patients with distant metastasis than in those without. In addition, M-PLA2 concentration was significantly higher in scirrhous carcinoma than in other histological types. No significant association was found between M-PLA2 concentration and age, menstrual status, tumour size, histological grade, vessel involvement or oestrogen receptor (ER) and progesterone receptor (PR) status. The expression of M-PLA2 mRNA was examined in a fibroadenoma, a stage IV breast cancer and its metastatic site of skin. Northern blot analysis showed a clear hybridisation band corresponding to M-PLA2 mRNA in both primary breast cancer and its metastatic site, while the fibroadenoma expressed a faint band corresponding to M-PLA2 mRNA. Breast cancer patients with high M-PLA2 concentrations exhibited significantly shorter disease-free and overall survival than those with low M-PLA2 concentration at the cut-off point of 5 ng 100 mg-1 protein, which was determined in a separate study. In multivariate analysis, M-PLA2 was found to be an independent prognostic factor for disease recurrence and death in human breast cancer. The possible significance of M-PLA2 expression in human breast cancer tissue is discussed.
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PMID:Overexpression of group II phospholipase A2 in human breast cancer tissues is closely associated with their malignant potency. 819 86

Immunohistochemical staining for oestrogen receptor (ER) has been carried out using antibody ER ID5 on 170 women who received first-line tamoxifen treatment for evaluable metastatic breast cancer. ER status had been determined some years previously, using a ligand-binding cytosol assay. The adequacy of the tissue used for the cytosol assay was always checked by histology on an adjacent block and was deemed to be typical of the tumour overall as was the block used for immunohistochemistry. Six different methods were used to assess the degree of staining and comparisons were made to determine which method gave the most clinically relevant results. Clinical outcome was assessed both in terms of duration of response to tamoxifen determined by log-rank analysis and type of response using the chi-squared test. The ER immunohistochemical assay gave superior results compared with the cytosol assay, with all of the subjective methods of assessment of staining giving statistically significant correlations with clinical outcome. The additional contribution of progesterone receptor (PR) staining with antibody NCL PGR was also studied.
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PMID:Immunohistochemical determination of oestrogen receptor: comparison of different methods of assessment of staining and correlation with clinical outcome of breast cancer patients. 891 24


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