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

Recent progresses of endocrine therapy for advanced and early breast cancer was reviewed. The mechanism (s) of an antiestrogen, tamoxifen has been noted at least partly as a stimulation of TGF beta action in ER-positive breast cancer cells. The Early Breast Cancer Trialists' Collaborative Group (EBC TCG) has recently reported the effectiveness of endocrine therapy, oophorectomy for premenopausal patients, and tamoxifen for pre- and post-menopausal patients in the adjuvant treatment for operable breast cancer patients. Two kinds of newly developed endocrine therapy were mentioned; LH-RH analogues for premenopausal patients, and aromatase inhibitors for postmenopausal patients. These agents decrease the plasma estrogen levels, acting like the ablative surgery, and make us more comprehensive combinations of endocrine therapy of breast cancer.
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PMID:[Recent progress of endocrine therapy in breast cancer]. 160 54

Aminoglutethimide is effective in the treatment of breast cancer in postmenopausal patients as a result of its inhibition of aromatase. Its use is complicated by a number of endocrine side-effects which include the inhibition of thyroxine synthesis and inhibition of 11-steroid and 21-steroid hydroxylases. When aminoglutethimide is used at the conventional daily dose of 1000 mg in combination with 40 mg of hydrocortisone these effects can result in clinically significant hypothyroidism and increases in the serum levels of oestrone in response to stimulation of adrenocorticotropic hormone (ACTH). In the current study it was found that with twice daily treatment at the low dose of 125 mg aminoglutethimide plus 20 mg hydrocortisone there was no significant increase in oestrone levels after ACTH stimulation. In addition there was little effect on thyroid function: serum levels of triiodothyronine and thyroxine were unaffected whilst there was a marginally significant (P less than 0.05) increase in thyroid-levels were confined to those patients with pretreatment values greater than 2.5 mU/L, the most marked effect being in 1 patient whose pretreatment level was already outside the normal range.
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PMID:Low-dose aminoglutethimide in postmenopausal breast cancer: effects on adrenal and thyroid hormone secretion. 165 77

A dispersed guinea pig adrenal system has been used to study the effect of the aromatase inhibitor rogletimide (RGL) on adrenal steroidogenesis. The ACTH-stimulated release of cortisol, 17-hydroxyprogesterone (17-OHP) and androstenedione (A) was measured following exposure of adrenal cells to RGL, or the other aromatase inhibitors aminoglutethimide (AG) and CGS 16949A. RGL at concentrations sufficient to cause 80-90% inhibition of placental microsomal aromatase had no effect on the release of all three steroids. In contrast, AG at 10(-5) M markedly reduced the output of all three steroids from these cells. CGS 16949A at 10(-6) M reduced the output of cortisol and increased the concentration of 17-OHP and A. These results indicate that RGL is unlikely to cause the suppression of cortisol synthesis which has been noted to occur with AG and CGS 16949A during the treatment of breast cancer patients.
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PMID:The effect of the aromatase inhibitor, rogletimide (pyridoglutethimide), on guinea pig adrenal cell steroidogenesis and placental microsomal aromatase activity: comparison with aminoglutethimide and CGS 16949A. 165 68

By modification of a recently developed method for separation of radio-labelled urinary oestrogens we were able to separate oestrogen metabolites and measure their isotope ratios in urine following injections of [3H]delta 4-androstenedione and [14C]oestrone. This method provides a useful tool for studying in vivo aromatisation of delta 4-androstenedione into oestrone in breast cancer patients before and during treatment with aromatase inhibitors.
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PMID:Measurement of aromatisation by a urine technique suitable for the evaluation of aromatase inhibitors in vivo. 166 31

The expression of aromatase was evaluated in 38 breast carcinomas by an immunohistochemical method (ABC) using an specific polyclonal antibody against human placental aromatase. Fifteen tumors (40%) showed significant immunoreactivity, as defined by cytoplasmic positivity of moderate intensity present in at least 15% of the cells. The results were correlated with the estrogen and progesterone hormone receptor status and several clinicopathologic parameters such as age, tumor size, lymph node status, and stage of the disease. There was a significant, but inverse, correlation between the aromatase activity and the estrogen receptor status (P = 0.04), indicating the likelihood of negative estrogen if substantial aromatase activity was present. No statistically significant correlation was found between the presence of intratumoral aromatase and the rest of the parameters studied (P greater than 0.7). Nor was there a correlation between the aromatase content of the tumors and the menopausal status. The degree of intratumoral heterogeneity of the aromatase content was minimal in six cases where multiple samples from each tumor were analyzed. This is the first study reporting the detection of aromatase in archival material from breast carcinomas using immunohistochemical techniques. The lack of biologic significance of its presence in breast cancer reported here and by others using biochemical assays should be validated in larger series with longer follow-up. The method described can be readily used for that objective.
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PMID:Detection of intratumoral aromatase in breast carcinomas. An immunohistochemical study with clinicopathologic correlation. 173 27

Tamoxifen is the endocrine treatment of choice for hormone-responsive early and advanced breast cancer. Newly developed biodegradable luteinizing hormone-releasing hormone super agonists represent a practical and effective treatment for metastatic disease in premenopausal women. Progestins or aromatase inhibitors are useful therapies in patients who relapse from antiestrogens. Currently, there is no indication that improved survival can be achieved by combined endocrine therapy or combined chemo-hormonal therapy.
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PMID:Pharmacologic manipulation of steroid hormones. Adjunctive therapies in cancer of the breast. 177 79

A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered. The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazo[1,5-alpha]pyridin-5-yl)benzonitrile monohydrochloride, 26a. In addition, the 6,7-dihydropyrrolo[1,2-c]imidazole (21a) and the 6,7,8,9-tetrahydroimidazo[1,5-alpha]azepine (21b) analogues were synthesized and evaluated. CGS 16949 A's ability to selectively inhibit aromatase (IC50 = 4.5 nM) over other cytochrome P-450 enzymes and suppress estrogen production when administered orally make it a suitable candidate to test the potential of an aromatase inhibitor in estrogen-dependent diseases including breast cancer.
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PMID:Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease. 182 37

The influence of a new aromatase inhibitor, CGS 16949A on peripheral aromatisation of androstenedione into oestrone was investigated in postmenopausal women with breast cancer. A mixture of 3H androstenedione and 14C oestrone was injected, and all urine was collected for the following 96 h. The isotope ratio was determined in the urinary oestrogen metabolites after isolation by HPLC. Eight patients were investigated before and during treatment with CGS 16949A. At a dose of 1 mg b.d. (eight patients) CGS 16949A inhibited aromatisation by a mean value of 82.4% (range 71.3 to 93.7%). When the drug dose was escalated to 2 mg b.d. (three patients) aromatisation was inhibited by a mean of 92.6% (range 90.6 to 95.8%), these results suggest that CGS 16949A at a dose of 1 mg b.d. causes submaximal aromatase inhibition in many patients, while a dose of 2 mg b.d. seems to result in greater than 90% aromatase inhibition. These data are consistent with previous observations that the higher dose is more effective in suppression of plasma oestradiol levels.
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PMID:The influence of CGS 16949A on peripheral aromatisation in breast cancer patients. 182 73

This updated literature review on heterosteroids and drug research has information on chemical structure, pharmacology, and effects. It first discusses the anti-inflammatory heterosteroids, such as mometasone furoate and cortivazol. It also covers heterosteroidal antimineralocorticoids and anabolic hetero derivatives. The review discusses at length the 19-norsteroid, mifepristone (RU-486), which exhibits antiprogestational activity and is being used for fertility control in women. It also has antiglucocorticoid activity and shows promise as a treatment of diseases characterized by muscle atrophy. In vitro studies indicate that mifepristone inhibits growth of breast cancer cell lines and of endometrial cancer cell lines. It has already exhibited growth inhibitory effects in some breast cancer patients. Discussions of mifepristone's pharmacokinetics and structural modifications of mifepristone follow. Danazol is an antigonadotropin and is used to treat endometriosis, benign breast disease, precocious puberty, hereditary angioneurotic edema, menorrhagia, some types of infertility, and gynecomastia. Danazol effects considerable changes in lipid metabolism. Other hormonal, antihormonal, and/or antifertility heterosteroids and/or aspects include androgen antagonists (e.g., cyproterone acetate), estrogen activity, antiestrogens, STS-557, and oximinosteroids. Heterosteroidal inhibitors of steroid hormone biosynthesis discussed are aromatase inhibitors, 5 alpha-reductase inhibitors, and 3 beta-hydroxysteroid dehydrogenase inhibitors (trilostane, epostane, and azastene). Heterosteroids affect the cardiovascular system, including the cardiac glycosides, antiarrhythmic agents, and antilipemic agents. Some heterosteroids affect central nervous system activity (e.g., RU-5135 causes convulsions in rodents). Pancuronium analogues and chandonium and analogues are neuromuscular blocking azasteroids. In addition to danazol and RU-486, several other antineoplastic heterosteroids exist (e.g., estramustine phosphate sodium, a prostate cancer drug).
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PMID:Heterosteroids and drug research. 184 48

A sensitive and specific quantitative assay has been developed for the determination of 4-hydroxyandrostenedione (4-OHA), a potent aromatase inhibitor used in the treatment of estrogen-dependent breast cancer. This steroid has a high first-pass metabolism and is extensively metabolized, mainly by glucuronidation. Plasma levels of unchanged 4-OHA are very low, even after high peroral doses. The analytical method is based on the addition of 17 alpha-ethinylestradiol (internal standard), liquid-liquid extraction from biological material followed by extractive alkylation with pentafluorobenzyl bromide and quantitation by gas chromatography. The method has been validated for sensitivity, accuracy and precision and was found to be suitable for application to pharmacokinetic and bioavailability studies of peroral formulations of 4-OHA.
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PMID:Determination of 4-hydroxyandrostenedione in plasma and urine by extractive alkylation and electron-capture gas chromatography. 187 5


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