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

Two human breast cancer cell lines (MCF-7 and MDA-MB-231) and one cell line derived from normal human breast (HBL-100) were examined for the presence of aromatase activity by determining the amounts of [3H]estradiol ([3H]E2) formed by cell cultures incubated with [3H]testosterone. Aromatase activity was demonstrable in both breast cancer cell lines, but estradiol synthesis was not observed in HBL-100 cultures. The [3H]E2 content of MCF-7 cultures rose as a function of incubation time and substrate concentration. Furthermore, [3H]E2 formation by this cell line was suppressed by several known inhibitors of human placental aromatase. These observations represent the first evidence that some lines of continuously cultured human breast cancer cells, like some human breast tumors, are capable of forming estrogen from an extracellular precursor steroid. Cultured breast cells may provide model systems for investigating the relative importance of intracellular estrogen formation in the regulation of human breast cancer cell growth.
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PMID:Estradiol formation from testosterone by continuously cultured human breast cancer cells. 45 46

Many cytotoxic agents have demonstrated activity in advanced breast cancer, the more active agents being cyclophosphamide and the anthracyclines doxorubicin and epirubicin. Combinations of drugs are generally superior to single agents in terms of response rate, duration of response and survival. The treatment of advanced breast cancer can be continued either until treatment failure, or for a limited time from either initiation of therapy or from the observation of complete response. Although these are issues of significant concern, data from randomised trials are limited, and so the question of optimal treatment duration remains open. Randomised trials comparing regimens that differ by a dose intensity factor of less than 2 have failed to demonstrate significant differences in efficacy between the dose levels. With higher doses, as applied in combination with colony-stimulating factors and bone marrow transplantation, response rates seem to increase, but whether this translates into improved survival has not yet been answered by the results of randomised trials. Approximately 30% of patients respond to endocrine therapy. From the results of randomised trials, which have compared the efficacies and toxicities of different endocrine modalities including combined endocrine therapy, single-agent tamoxifen is generally considered as the preferred first-line treatment, leaving progestins and aromatase inhibitors as alternatives for second-line endocrine therapy in responders. In the majority of trials, chemotherapy combined with endocrine therapy has given improved response rates compared with chemotherapy alone, but the differences have not generally been translated into prolonged survival with combined modalities. This gives rise to the question of the optimal sequence of chemotherapy and endocrine therapy, a subject needing further evaluation in future trials.
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PMID:Systemic therapy of advanced breast cancer. 128 47

The effect of a number of steroids, growth factors, and peptides on aromatase activity in two estrogen receptor positive breast cancer cell lines (MCF7 and T47D) was investigated. The cells were incubated in Dulbecco's minimum essential medium containing phenol red and 10% fetal calf serum. Pronounced differences in basal aromatase activity and different responses to the addition of experimental agents were found in the two cell lines. Aromatase activity in MCF7 cells was significantly stimulated by phorbol 12,13-diacetate [PDA], dibutyryl cyclic AMP [(Bu)2cAMP], transforming growth factor alpha, and epidermal growth factor individually and PDA and (Bu)2cAMP in combination, while it was inhibited by dexamethasone and unaffected by transforming growth factor beta, fibroblast growth factor, platelet-derived growth factor, prolactin, and tamoxifen. Addition of cortisol to MCF7 cells had no effect on aromatase activity at 1 nM, caused suppression of activity at 10 nM and stimulated activity at 100 nM. Aromatase activity in T47D cells was stimulated by transforming growth factor alpha, epidermal growth factor, platelet-derived growth factor, prolactin, dexamethasone, and cortisol individually and PDA and (Bu)2cAMP in combination. It was unaffected by transforming growth factor beta, PDA, (Bu)2cAMP, and fibroblast growth factor. These findings suggest that aromatase activity is induced by agents which stimulate cyclic AMP-dependent protein kinases [e.g., (Bu)2cAMP] and that this effect is potentiated by factors which stimulate protein kinase C [e.g., PDA]. The effect on aromatase activity of growth factors, the actions of which are believed to be mediated by receptors linked to tyrosine kinase activity, is not as clearly defined, with a factor causing stimulation, inhibition, and no change in activity depending on the tissue concerned. Further insight into these differences will require resolution of the molecular mechanisms that mediate the actions of stimulatory and repressive growth factors on aromatase activity of oestrogen-producing cells.
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PMID:Steroid and growth factor modulation of aromatase activity in MCF7 and T47D breast carcinoma cell lines. 131 30

We have previously shown that human breast cancer is autonomous in the regulation of its intra-tissue oestradiol concentration. Breast fatty tissue does not have this capacity, but rather reflects changes in the peripheral oestradiol concentration. To further evaluate the relative contribution of breast cancer and fatty tissue to the maintenance of tumour oestradiol we investigated whether a tumour-directed gradient in aromatase activity and oestrogen levels existed in mastectomy specimens. No such gradient was found, however, for aromatase, oestrone, oestradiol and their sulphates. Aromatase activity (expressed per gram of tissue) and the concentrations of oestradiol, oestradiol sulphate and oestrone sulphate were higher in tumour than in breast fatty tissue. Fatty tissue had a higher oestrone concentration. It is tentatively concluded that breast tumour aromatase activity is more important for the maintenance of tumour oestradiol levels than aromatase in breast fatty tissue.
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PMID:On the significance of in situ production of oestrogens in human breast cancer tissue. 131 86

Therapeutic access in the treatment of breast cancer with the antiestrogen tamoxifen has been established by world-wide clinical trials since the drug was introduced by Cole et al, in 1971. In recent years, however, a new series of antiestrogens (the derivatives of tamoxifen) such as trioxifene, toremifene and droloxifene have been studied with regard to clinical efficacy as a first-line treatment for postmenopausal patients with breast cancer and occasionally even for patients who previously responded to tamoxifen and then relapsed. Luteinizing hormone releasing hormone (LHRH) agonists are now available for premenopausal patients that will produce a medical castration, when given continuously, by down-regulation of the pituitary LHRH receptors. Four compounds, leuprolide, buserelin, tryptorelin and goserelin have been available for clinical use, but goserelin (Zoladex) is now widely used by long-acting depot preparations, which are given subcutaneously once every 4 weeks. Another series of drugs which inhibit estrogen synthesis in postmenopausal patients and are termed "aromatase inhibitors" have been developed. The pure aromatase inhibitors newly developed include two types of both a steroidal compound (4-hydroxyandrostenedione) and a non-steroidal one which is a tetrahydroimidazopyrimidine derivative (CGS 16949A). This review describes the pharmacological and clinical aspects of these new agents.
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PMID:[New drugs in endocrine treatment of breast cancer]. 132 43

Established human mammary tumor cell lines constitute an important tool in the study of breast cancer. The aim of this work was to isolate and characterize two new mammary tumor cell lines, JCK and GCS, which were obtained from the pleural effusion and ascitic fluid, respectively, from two breast cancer patients. Both cell lines had some properties of transformed cells, namely immortalization and growth in soft agar. The carcinoma cells presented epithelial morphology shown by light and electron microscopy, and antigenic properties shown by different tumor markers such as a cytokeratin cocktail, carcinoembryonic antigen, epithelial membrane antigen, and human milk fat globule membrane antigen. A significant increase was also found (P greater than 0.05) in cell growth and 3H-thymidine incorporation into DNA in the JCK and GCS cell lines in the presence of 17 beta estradiol at concentrations of 10(-9) and 10(-7) M, respectively, after 5 days in culture. These cells presented estradiol receptor levels which were similar in the biopsies and the resulting cell lines. The aromatase activity was also similar in the JCK cell line and the original patient biopsy. However, there was a considerably higher aromatase activity in the GCS cell line than in the biopsy specimen. Southern hybridizations with the neu oncogene showed an additional 12 kb fragment in both cell lines, as also seen in patients with breast cancer. We conclude from these studies that this in vitro system may provide us with a way to study metastatic cells and improve clinical management of breast cancer patients.
Breast Cancer Res Treat 1992
PMID:New cell lines of human breast cancer origin. 132 92

Means and the currently accepted principles of hormone therapy of breast cancer have been summarized on the basis of data from references. Fields of application and adverse effects of anti-oestrogens, aromatase inhibitors, gestagens, gonadotrophin-releasing, and androgenic hormones have been analysed. Drugs with various mechanisms of action and available in Hungary have been discussed.
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PMID:Hormone therapy in breast cancer. 134 21

Progress in the treatment of breast cancer developed along multiple directions of research during the last decade. The concept of dose-intensity was addressed through retrospective analyses and prospective randomized trials. It was confirmed that dose-intensity correlates with higher response rates, but the effect of dose-intensive treatments on survival still needs to be established. Several new cytotoxic drugs have appeared during the last several years. Taxol, navelbine, and anthrapyrazole CI-941 have been found to have major efficacy against breast cancer, with response rates exceeding 50%. Amonafide, lonidamine, and elliptinium analogs were also shown to be effective, although to a lesser degree. Antiestrogen analogs, new aromatase inhibitors, and LHRH analogs are recent developments that are changing the face of hormonal therapy. Monoclonal antibodies are being developed and evaluated for tumor imaging applications and as vehicles for specific antitumor agents (cytotoxics, radioisotopes, and toxins). Expanding knowledge about the basic biology of breast cancer has led to the identification of growth factors and their receptors, which may be exploited for therapeutic purposes in the not too distant future.
Breast Cancer Res Treat 1992
PMID:Overview of new treatments for breast cancer. 135 16

More than 45,000 women will die of metastatic breast cancer in the United States in 1991. Endocrine therapy remains a major option for treatment of such patients, and results in complete plus partial response rates of 30% with a median duration of approximately one year. Postmenopausal status, increased age, a prolonged disease-free interval, bone and soft tissue metastases, and positive estrogen and progesterone receptors are all associated with an increased response to endocrine therapy. The use of additive hormonal therapy, specifically antiestrogens, progestins, and aromatase inhibitors, have replaced surgical ablative procedures in the majority of patients; response rates to antiestrogen therapy, progestin therapy, and aromatase inhibitors are similar, but antiestrogens have generally been associated with the most favorable therapeutic index. At present, there is no convincing evidence that either combinations of endocrine therapies or endocrine therapy combined with chemotherapy are associated with an improvement in survival for patients with metastatic disease. Future research efforts directed at defining the molecular mechanisms of endocrine activity should facilitate clinical trials of newer and potentially more effective agents. All patients with metastatic breast cancer should be considered for at least one trial of endocrine therapy provided their metastatic disease is not rapidly progressive or life-threatening.
Breast Cancer Res Treat 1992
PMID:Endocrine therapy for advanced breast cancer: a review. 138 23

Aminoglutethimide was the first aromatase inhibitor to be used in breast cancer therapy but, since it interacts with the synthetic glucocorticoids, hydrocortisone must also be given as a replacement. The most important side-effects of aminoglutethimide are at the level of the central nervous system. Other aromatase inhibitors with greater potency and selectivity are being developed. Pyridoglutethimide, a compound resulting from modifications to the structure of aminoglutethimide, seems to be devoid of sedative properties according to preliminary tests on the central nervous system. 4-Hydroxyandrostenedione is significantly more potent and better tolerated than aminoglutethimide. Fadrozole (CGS 16,949 A) is 200-400 times more potent than aminoglutethimide and is now in phase II of its clinical development. CGS 20,267 has no effect on adrenal steroidogenesis and is currently in phase I of its clinical development. Availability of newer aromatase inhibitors could make a worthwhile contribution to endocrine therapy in breast cancer.
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PMID:Aromatase inhibitors: clinical pharmacology and therapeutic implications in breast cancer. 138 68


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