Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Department of National Health and Welfare's special advisory committee are closely monitoring women, who used DES(diethylstilbestrol) for protection of pregnancy, and their offspring. DES daughters have an increased risk of benign abnormalities of the genital tract and, infrequently, vaginal or cervical cancer. Prenatal exposure of males to DES have shown a low frequency of epidiymal cysts, hypoplastic testes, induration of the testicular capsule, and impairment of spermatogenesis, sperm maturation, and accessory gland secretion. Women who used DES during their pregnancy may possibly have an increased risk of breast cancer although the incidence is not statistically significant. The advisory committee recommends that DES and other estrogenic drugs not be used during pregnancy for treatment of threatened abortion due to the possible abnormalities of the fetus. Instead the committee suggests that DES be used for patients with estrogen-responsive metastatic breast cancer or advanced prostate cancer.
 ...
PMID:Diethylstilbestrol: risks of malignant disease and congenital malformations. 45 96

Endocrine hormone treatment has been found to be effective in treating metastatic breast cancer in 20-40% of the cases. The effectiveness of this treatment can be predicted to a certain extent by determining whether the hormone receptors in the tumor tissue react positively or negatively when incubated with highly active hormones, e.g. H3-17 beta-estradiol. Estrogen receptors are found in 60-70% of primary tumors and 40-50% of tissue samples from metastatized tumors. Estrogen receptors are more frequently found in post-menopausal women than in women who are still menstruating. Progesterone receptors have been found in 20-40% of all investigations undertaken, androgen receptors in 20-30%, and corticosteroid receptors in 20-50%. A remission rate of 56% has been achieved after endocrine therapy of those with positive estrogen receptor tests, compared to 10% among those with negative tests. The correlation between the receptor test results and (the success of) endocrine therapy is not very high; this could be a factor determined by the cellular constitution of a tumor. The remission rate is 75% among patients with positive receptor tests for both estrogen and progesterone. Faulty lab techniques could be responsible for low correlation. Determination of the receptor activity of both the primary tumor and its metasases, or immunological or immunohistological determination of receptor activity may improve the usefulness of the test in determining tumor reaction to endocrine hormone treatment.
 ...
PMID:[The clinical value of hormone receptors in the treatment of breast neoplasms]. 54 83

Estrogen and progesterone receptors were studied in fine-needle aspiration biopsy specimens of 56 patients with primary, recurrent, or metastatic breast carcinoma. The ligands, 17 B-estradiol-6-carboxymethyloxine-bovine serum albumin fluorescein isothiocyanate (FITC-BSA estradiol) and hydroxyprogesterone hemisuccinate bovine serum albumin tetramethyl rhodamine isothiocyanate (TMRITC-BSA progesterone), were used in the fluorescent cytochemical method. The findings obtained from the aspirated cells with the use of the fluorescent cytochemical technique were compared with results obtained from the cell population of the same tumor after removal with the use of both the fluorescent cytochemical technique and the biochemical dextran-coated charcoal (DCC) assay. For the needle aspirates, there was 89% concordance for estrogen receptor and 86% concordance for progesterone receptor between biochemical and cytochemical results. A high degree of correlation was also demonstrated between fine-needle aspirates and imprint preparations with the use of the cytochemical technique. This study suggests that the fluorescent cytochemical technique is an effective tool in assessment of estrogen and progesterone receptor content in fine-needle aspirates of primary and metastatic breast cancer. The fluorescent cytochemical technique can be performed easily at community hospitals and is well suited for specimens of insufficient size for biochemical assay.
 ...
PMID:Fluorescent cytochemical detection of estrogen and progesterone receptors in breast fine-needle aspirates. 198 50

Diethylstilbestrol (DES) can induce a recruitment into the proliferative pool of previously resting breast cancer cells in vivo. In order to verify if estrogenic recruitment could result in a larger tumor cell killing by chemotherapy, 117 patients with metastatic breast cancer were randomized to receive CEF (cyclophosphamide, 600 mg/m2; epidoxorubicin, 60 mg/m2; and 5-fluorouracil, 600 mg/m2 on day 1); DES-CEF (cyclophosphamide, 600 mg/m2 on day 1; DES, 1 mg orally on days 5, 6, and 7; and epidoxorubicin, 60 mg/m2, and 5-fluorouracil, 600 mg/m2, on day 8) every 21 days. No significant difference in objective response rates, survival, or progression-free survival was seen between the two regimens. Patients in the DES-CEF arm experienced a higher complete response (CR) rate (24.1% v 16.1%), which reached statistical significance in the case of soft-tissue metastasis (48% v 27.3%; P less than .05) and estrogen receptor-negative tumors (35.7% v 11.1%; P less than .025). Survival and progression-free survival of patients refractory to treatment were not worsened by estrogenic recruitment. In the subset of patients failing after adjuvant polychemotherapy, DES-CEF unexpectedly induced a significantly longer survival (greater than 802 days v 375 days; P = .029) and progression-free survival (239 days v 192 days; P = .041) than CEF. The DES-CEF regimen was more myelotoxic, and 43.3% of the DES-CEF cycles had to be delayed because of leukopenia in comparison with 11.8% of the CEF cycles (P less than .0001). In conclusion, chemotherapy with estrogenic recruitment was able to induce more CRs in certain subsets of patients and a significant prolongation in survival and progression-free survival of patients failing after adjuvant polychemotherapy. These results have been achieved despite a significantly lower dose intensity of chemotherapy.
 ...
PMID:Conventional versus cytokinetic polychemotherapy with estrogenic recruitment in metastatic breast cancer: results of a randomized cooperative trial. 354 11

Estrogen biosynthesis occurs not only in reproductive tissues of the female but also in such diverse sites as testes, adipose and muscle. Our rationale for the clinical use of aromatase inhibitors is that compounds interacting with aromatase in all tissues could provide both selective and effective inhibition of estrogen production. The most potent inhibitor identified by us to date is 4-hydroxyandrostene-3,17-dione (4-OHA). This compound causes rapid competitive inhibition followed by irreversible inactivation of aromatase. Treatment of rats with 4-OHA results in inhibition of ovarian aromatase and estrogen secretion, accompanied by marked regression of carcinogen induced mammary tumors. Using rhesus monkeys, marked inhibition of peripheral aromatization by 4-OHA was also demonstrated. The first clinical study with a selective aromatase inhibitor was recently carried out using once weekly injections of 500 mg 4-OHA in 60 postmenopausal patients with advanced metastatic breast cancer and unselected for the presence of estrogen receptors. The mean serum estradiol level reduced to 36% of pretreatment values for at least 4 months. No effect of treatment on gonadotropin levels occurred indicating that the reduction in estrogen levels was due to inhibition of peripheral aromatization. In spite of the fact that all patients had relapsed from previous therapy, complete or partial tumor regression occurred in 30% of patients while 15% had static disease. Although the optimum dose of 4-OHA has not yet been established, this aromatase inhibitor appears to be of value in treating postmenopausal breast cancer and may be beneficial in other diseases associated with estrogens.
 ...
PMID:Aromatase inhibitors and their potential clinical significance. 380 67

Estrogen (ER) and progesterone (PgR) receptors were assayed by histochemistry in primary, recurrent, and metastatic breast cancer. Ligand-conjugates composed of 17 beta-estradiol and 11 alpha-hydroxyprogesterone covalently linked to bovine serum albumin and labelled with fluorescein isothiocyanate were employed. Results were compared with those of conventional biochemical receptor assays and correlated for ER in 92% of 314 tumors and for PgR in 86% of 86 specimens. ER and PgR determinations by both assay systems were correlated with clinical response to various endocrine therapies in 40 women with Stage IV disease. The histochemical assay enabled successful prediction of response in 80% of cases including eight which could not be fully analyzed biochemically.
 ...
PMID:Histochemical assay of estrogen and progesterone receptors in breast cancer: correlation with biochemical assays and patients' response to endocrine therapies. 625 56

The relation between estrogen- and progesterone-binding receptors and the metastatic behavior of breast carcinoma was examined by reviewing autopsy findings in 25 subjects with metastatic breast cancer at Johns Hopkins Hospital for whom the results of estrogen- and/or progesterone-binding assays were available. Regardless of receptor status, patients treated with hormone therapy had prolonged survival (p less than 0.05), but had greater tumor burden at autopsy (p less than 0.05). The distributions of metastases differed for receptor-positive versus receptor-negative tumors. Estrogen-positive tumors metastasized more frequently to thyroid and/or parathyroid glands (p less than 0.01). Estrogen-negative tumors metastasized more extensively to the leptomeninges (p less than 0.01). Progesterone-positive tumors metastasized more frequently to myocardium (p less than 0.01), small bowel (p less than 0.01), urothelial structures (p less than 0.05), and thyroid and/or parathyroid glands (p less than 0.05). These differences in the distributions of metastases may reflect different tissue preferences in metastasizing breast carcinoma cells with estrogen- and/or progesterone-binding receptors. In this regard, perhaps patients with estrogen-negative tumors should be monitored closely for the development of carcinomatous meningitis, because this form of central nervous system involvement is a frequent cause of death among patients with breast carcinoma.
 ...
PMID:Estrogen and progesterone receptors in prediction of metastatic behavior of breast carcinoma. 669 51

Estrogen receptors in breast tumors were assayed in 55 premenopausal women undergoing bilateral oophorectomy and in 120 postmenopausal women undergoing bilateral adrenalectomy for treatment of metastatic breast cancer. The data show that 20 (60%) of the 32 patients with estrogen receptor-positive (ER+) tumors had objective remission after oophorectomy, and 44 (51%) of the 87 patients with ER+ tumors responded to adrenalectomy. In contrast, of those patients with estrogen receptor-negative (ER-) tumors, only 3% had an objective remission following oophorectomy and 9% following adrenalectomy. It is concluded that major endocrine ablative procedures are not justified in patients with ER- tumors. The data also conclusively demonstrate the significance of 4S receptors in predicting the response to endocrine therapy. In this study, it was found that although the response rate to endocrine ablation was substantially higher (71-83%) in patients whose tumors contained both estradiol and progesterone receptors, between 50 and 60% of ER+ tumors lacking progesterone receptors had objective remission after endocrine ablative therapy.
 ...
PMID:Steroid receptors and response to endocrine ablations in women with metastatic cancer of the breast. 744 20

The pharmacologic inhibition of aromatase activity has been the focus of clinical trials in patients with advanced stage breast cancer. Recent developments with imidazole compounds that inhibit aromatase activity suggest their clinical use as potent inhibitors of estrogen biosynthesis in postmenopausal breast cancer patients. In this Phase I, open-label, dose-range finding study, we examined the inhibitory potency of CGS 20267 on blood and urine levels of estradiol, estrone and estrone sulfate in 8 patients with metastatic breast cancer. Studies included evaluation of adrenal and thyroid function to look for evidence of general hydroxylase inhibition at dose levels effective for aromatase blockade. Patients were administered CGS 20267 at doses of 0.1 and 0.25 mg, once a day in ascending doses over a 12-week period. Preliminary data reveal that CGS 20267 elicits a striking suppression in plasma estradiol, estrone and estrone sulphate which was observed in some patients as quickly as within 24 h of the first dose. Estrogen suppression of over 90% was achieved within 2 weeks of therapy. No alterations in either baseline or ACTH (cortrosyn) stimulated cortisol and aldosterone levels were observed through the 12 weeks of therapy. In addition, 24 h urine sodium and potassium values were not appreciably altered during therapy. We conclude that CGS 20267 is a potent, specific inhibitor of estrogen biosynthesis in postmenopausal patients with metastatic breast cancer and effectively reduces blood and urine estrogens to undetectable levels.
 ...
PMID:The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer. 847 85

Acquired resistance to antiestrogens is a major problem in the clinical management of initially endocrine responsive metastatic breast cancer. We have shown previously that estrogen-independent and -responsive MCF7/LCC1 human breast cancer cells selected for resistance to the triphenylethylene tamoxifen produce a variant (MCF7/LCC2) that retains sensitivity to the steroidal antiestrogen ICI 182,780 (N. Brunner et al., Cancer Res., 53: 3229-3232, 1993). We have now applied stepwise selections in vitro from 10 pM to 1 microM ICI 182,780 against MCF7/LCC1 and obtained a stable ICI 182,780-resistant variant designated MCF7/LCC9. In contrast to 4-hydroxytamoxifen-selected MCF7/LCC2 cells, MCF7/LCC9 cells exhibit full cross-resistance to tamoxifen, despite never having been exposed to this drug. Significantly, tamoxifen cross-resistance arose early in the selection, appearing following selection against only 0.1 nM ICI 182,780. Although limited resistance to ICI 182,780 also was observed, full ICI 182,780 resistance was not detected until the selective pressure increased to 100 nM ICI 182,780. Cross-resistance to tamoxifen persisted throughout these additional selections. Despite their antiestrogen cross-resistance, MCF7/LCC9 cells retain a level of estrogen receptor expression comparable to that of their parental MCF7/LCC1 cells. Whereas MCF7/LCC1 cells retain an estrogen-inducible expression of progesterone receptors, MCF7/LCC9 cells exhibit an up-regulated expression of both progesterone receptor mRNA and protein that is no longer estrogen responsive. Estrogen-independent and -responsive components of the MCF7/LCC9 phenotype are apparent in vivo. These cells form slowly growing tumors in ovariectomized athymic nude mice but respond mitogenically upon estrogenic supplementation. The in vivo growth of MCF7/LCC9 tumors is not affected by treatment with ICI 182,780. Although there is some evidence of tamoxifen stimulation of tumor growth, this did not reach statistical significance. If this pattern of cross-resistance occurs in some breast cancer patients, administering triphenylethylene antiestrogens as a first-line therapy with a cross-over to steroidal compounds upon recurrence may be advantageous.
 ...
PMID:MCF7/LCC9: an antiestrogen-resistant MCF-7 variant in which acquired resistance to the steroidal antiestrogen ICI 182,780 confers an early cross-resistance to the nonsteroidal antiestrogen tamoxifen. 927 17


1 2 3 Next >>