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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Endocrine therapy for advanced breast cancer: a review. 138 23

Breast cancer is the most common malignant tumor among women, comprising an estimated 24% of all cancer cases and 18% of all cancer deaths. At least half of the patients with primary breast cancer will ultimately die by metastatic disease. The tumor characteristics, the natural course of the disease and the response to therapy vary strongly. A number of recently detected cell biological parameters such as oncogenes/suppressor genes, growth factors and secretory proteins are more or less important prognostic factors, because they influence the characteristics and behavior of a tumor with respect to metastatic pattern, extent of cellular differentiation, growth rate and response to treatment. However, there is no clear consensus how best to identify patients at high or low risk. In our experience c-myc amplification and pS2 protein are strong prognosticators for relapse rate, while in advanced disease (apart from a negative estrogen/progesterone receptor/pS2 status) amplification of HER2/neu is a good prognosticator for failure to endocrine therapy. In the diagnosis of breast cancer, in vivo imaging of tumors by labeled hormones or other factors also forms a new development which might have implications for treatment too. With respect to treatment both endocrine and chemotherapy can cure a minority of patients with micrometastases, but in patients with advanced disease only a prolongation of (progression-free) survival can be reached. Response rates decrease with increasing tumor load. In the past decade a number of interesting new endocrine agents has been developed such as new (pure) (anti)steroidal agents, vitamins, aromatase inhibitors, analogs of peptide hormones, prolactin inhibitors and growth factor antagonists. However, less is known on the (potential) interaction between hormones, chemotherapeutic agents, retinoids, cytokins, growth factor antagonists and irradiation. Rapid detection of new powerful combination therapies are needed to improve treatment results during the nineties.
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PMID:Clinical breast cancer, new developments in selection and endocrine treatment of patients. 144 97

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

Forty-six postmenopausal women with either locally advanced or metastatic breast cancer were treated with the aromatase inhibitor CGS 16949A in three different daily doses (0.3 mg, 0.6 mg and 0.9 mg total daily dose). 41 patients (89%) were pretreated by endocrine treatment for metastatic disease; 30 of these 41 were also pretreated with chemotherapy. Of the remaining 5 patients (11%) 3 were previously treated with chemotherapy alone and 2 were not pretreated. Evaluable sites of disease were: skin and soft tissue (including local recurrence) in 34, bone in 31, lung in 14 and viscera in 13 instances, respectively. 1 PR (3%) and 9 stable diseases (24%) were observed in the 37 patients assessable for response. All but two of these results were observed in the 0.9 mg group. Time to progression was 14 months for the patient showing a PR, and the median time to progression for those with stable disease was 6 months (range 6 to 23 months). Plasma estradiol and estrone levels were measured in patients receiving the daily dose of 0.6 mg (n = 4) and 0.9 mg (n = 15). The estrone levels decreased from a mean of 23.1 pg/mL (SD 17.1) to 10.5 pg/mL (SD 6.6) in the 0.6 mg-group and from 21.2 pg/mL (SD 18.9) to 9.1 pg/mL (SD 5.5) in the 0.9 mg-group within 4 days of drug administration (p less than 0.0001 from baseline in both groups, with no significant difference between doses).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CGS 16949A, a new aromatase inhibitor in the treatment of breast cancer--a phase I study. 215 May 91

Endocrine therapy is a major treatment modality for the systemic management of breast cancer. In comparison with alternatives such as chemotherapy, hormone manipulations have the advantage of lower toxicity but suffer from the disadvantages of producing responses in only 30-40% of patients with metastatic disease and seldom being curative. Nevertheless in recent years there have been significant advances in the endocrine treatment of breast cancer which have stemmed from a better understanding of the sources from which breast tumours may be supplied with hormones, the mechanism by which hormones regulate tumour proliferation and the more accurate identification of hormone sensitive tumours. As a result agents such as antioestrogens, aromatase inhibitors. LHRH agonists have largely superseded surgical and radiological ablation of endocrine organs. The major reduction in morbidity associated with these medical regimes means that they are much more acceptable to patients and may be used as adjuvants to local treatment of the breast in patients with "earlier" stages of the disease. At the same time patients can now be offered rational treatment selected on the basis of tumour biology rather than on more empirical criteria. The aims of this review are to provide details of the research which has led to this progress in endocrine treatment of breast cancer and to put into perspective the prospects for further advances.
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PMID:Endocrine treatment for breast cancers: biological rationale and current progress. 227 30

Aromatase activity has been measured in human breast cancers by incubating tumour minces with [7 alpha-3H]testosterone and characterizing purified oestradiol (E2) fractions by chemical derivative formation. Of 247 primary tumours, 178 showed evidence of oestrogen biosynthesis, levels varying between 0.5 and 12.5 fmol E2 produced/h/g tissue. These values were quantitatively small but at least comparable with those in other peripheral tissues. There was no correlation between presence or level of aromatase activity and the histopathology of the tumours although oestrogen biosynthesis was more likely to be present in more cellular tumours. Aromatase activity was also unrelated to age, menopausal status, lymph node status and T stage of the patient from which the tumour was derived. In a subgroup of patients presenting without clinical evidence of distant metastatic disease, no significant relation was detected between tumour aromatase and disease-free interval, but tumours without aromatase activity were associated with increased survival at 36 months after primary treatment. A statistically significant correlation was also detected between the presence of tumour aromatase and oestrogen receptors. Furthermore, in small subgroups of patients with "advanced" breast cancer tumour aromatase was related to response to aminoglutethimide but not tamoxifen therapy. Whilst these results do not conclusively define a role for local synthesis of oestrogen in the progression of breast cancer, this possibility still exists and further studies on tumour aromatase are warranted.
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PMID:Relationship between tumour aromatase activity, tumour characteristics and response to therapy. 228 81

There is only one previous report of an estrogen-secreting adrenal tumor occurring in a woman during reproductive years. Our patient presented with mild hirsutism associated with menstrual bleeding every 3-6 weeks. The occurrence of apparently intermenstrual bleeding prompted an evaluation of estrogen levels. Markedly elevated plasma estrone levels were found (860-2305 pmol/L; normal, 50-340). Lesser relative elevations in 11-deoxycortisol and androstenedione were noted. Computed tomographic scanning of the adrenal glands identified a large tumor, which was subsequently resected. Estrone levels fell to 120 pmol/L, and all other abnormalities were corrected. Eighteen months after adrenalectomy, ovulation occurred regularly, and steroid levels were entirely normal. Steroid production in a cell suspension made from tissue obtained from the 190-g tumor was compared with that occurring in normal human adrenal cells. The production of estrone by the tumor cells was 40-fold greater than that by normal adrenal cells. There was also a mild excess of 11-deoxycortisol produced by tumor cells, but the tumor cells were less than 50% as efficient as normal cells in producing cortisol, dehydroepiandrosterone, androstenedione, testosterone, and dehydroepiandrosterone sulfate. Examination of the steroid profile in plasma occurring in three other patients with adrenal tumors reveals that while elevations in estrone occur frequently, this is usually due to the peripheral conversion of very high levels of androstenedione. Estrone, androstenedione, and 11-deoxycortisol plasma levels were elevated in all four patients; dehydroepiandrosterone sulfate was elevated in only two of four patients. After resection of one of these tumors, all steroid levels remained normal despite the occurrence of extensive metastases. These observations confirm the difficulty of making a diagnosis of estrogen excess in a woman during reproductive years because of the paucity of physical signs. The acquisition of aromatase activity was clearly demonstrated by tumor cells from our patient in vitro. Elevated plasma concentrations of estrone, androstenedione, and 11-deoxycortisol provide useful markers for adrenal tumors, but no one steroid can be relied upon in all tumors, and metastases may lack the steroidogenic capabilities of the primary tumor.
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PMID:Steroidogenesis in an estrogen-producing adrenal tumor in a young woman: comparison with steroid profiles associated with cortisol- and androgen-producing tumors. 229 37

Breast cancer is a highly heterogeneous disorder with regard to biologic and clinical characteristics. Identification of patients with different biologic subtypes is important both prognostically and therapeutically. The recent introduction of estrogen and progesterone receptor measurement has considerably increased our ability to identify patients with hormone-dependent tumors who are likely to respond to endocrine therapy and enjoy a longer survival. Assessment of the tumor growth fraction by autoradiographic or flow cytometric methods and measurement of EGF receptors in tumor specimens are likely to produce additional independent information on the clinical outcome of patients with breast cancer. The endocrine therapy of breast cancer has been greatly facilitated with the introduction of newer forms of therapy such as antiestrogens and aromatase inhibitors. These forms of treatments are well established, not only in patients with metastatic disease but also in selected subgroups of women with operable breast cancer following surgery. In view of its low toxicity and ease of administration, modern endocrine therapy has obviated the need for major ablative procedures such as surgical adrenalectomy and hypophysectomy. Unfortunately, duration of response and survival have not been prolonged by these newer endocrine treatments when compared with traditional hormonal therapy. Thus, new treatment strategies need to be developed, since current therapy does not cure any patient with advanced disease and at best only a small fraction of women with early breast cancer. Hormonally induced manipulation of tumor cell kinetics may provide a tool to enhance the efficacy of cytotoxic chemotherapy, in both metastatic as well as locally advanced disease. This potential approach needs to be further evaluated in prospective randomized clinical trials. Prostate cancer is the male counterpart of hormone-dependent neoplasia. Conventional therapy of this malignancy consists of surgical or medical castration. However, despite a high initial response rate, disease progression invariably occurs with poor response to secondary forms of therapy. Potential new treatment strategies currently being tested in the attempt to improve clinical outcome include simultaneous early blockade of both adrenal and testicular androgens as well as hormonally induced tumor cell growth synchronization and recruitment prior to administration of cytotoxic chemotherapy.
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PMID:Endocrine therapy of breast and prostate cancer. 266 86

Application of aromatase inhibitors to the treatment of conditions in which estrogen plays, a role is discussed. Studies in vitro demonstrate that 4-hydroxyandrostenedione (4-OHA) is a potent inhibitor of aromatase. The compound reduces ovariant estrogen production and causes regression of carcinogen (DMBA)-induced mammary tumors in the rat. In the rhesus monkey, 4-OHA was also shown to inhibit peripheral aromatization. To date 58 postmenopausal breast cancer patients with advanced metastatic disease have received 500 mg im weekly while 31 patients received 250 mg 4-OHA orally per day. Estradiol levels were significantly reduced in all patients from a mean of 7.2 + 0.8 pg/ml to 2.8 + 0.3 pg/ml. Of patients receiving 4-OHA im 27% had partial or complete responses and in 10% of patients the disease was stabilized. Similar responses occurred in the patients receiving 4-OHA orally. These results suggest that 4-OHA is effective and that this compound and other aromatase inhibitors could be valuable new additions to the treatment of breast cancer.
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PMID:Aromatase inhibitors: basic and clinical studies. 332 May 68

4-hydroxyandrostenedione, a potent inhibitor of the aromatase (oestrogen synthetase) system, was given to 11 patients with metastatic breast cancer. After a single 500 mg intramuscular injection a sustained reduction of serum oestradiol was observed for at least 1 week in all patients in whom the steroid was measured. 4 patients responded to treatment for periods of up to 4 months, and healing of bone metastases and reduction in size of soft-tissue metastases was evident. The only side-effects were pain at the injection site and hot flushes. 4-hydroxyandrostenedione is a new and specific aromatase inhibitor which shows promise in the treatment of patients with metastatic breast cancer.
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PMID:4-Hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. 615 Feb 77


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