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

Fadrozole Hydrochloride (CGS 16949A) and Letrozole (CGS 20267), are two of the newest non-steroidal, orally active aromatase inhibitors currently being evaluated as second line treatment of patients with hormone dependent forms of metastatic breast cancer. In a phase I clinical efficacy study, we examined the ability of these two imidazole derivatives to suppress the synthesis of estrogen in a cohort of postmenopausal patients with metastatic breast cancer. Both medications at relatively low doses were potent and rapid inhibitors of aromatase activity as evidenced by their ability to suppress the level of blood and urine estradiol and estrone as well as blood estrone sulfate in these patients. Letrozole appeared to be the more potent of the two, with over 95% suppression of both plasma and urinary estrogens observed within 2 weeks of therapy. Letrozole appeared to be more selective than Fadrozole in inhibiting aromatase activity in that no compromise in cortisol and aldosterone output was evident with Letrozole therapy at all of the doses tested, a compromise clearly seen with Fadrozole. The inhibition of aromatase activity by these imidazole derivatives as second line therapy for patients with hormone dependent breast cancer appears to be a favorable alternative form of hormone ablative therapy and holds considerable promise for the treatment of this malignancy.
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PMID:Effects of Fadrozole (CGS 16949A) and Letrozole (CGS 20267) on the inhibition of aromatase activity in breast cancer patients. 794 8

30 postmenopausal patients with metastatic breast cancer were treated with three different doses of fadrozole hydrochloride (CGS 169 49A), a non-steroidal competitive aromatase inhibitor. The effect of 0.5, 1 and 2 mg given twice daily upon the levels of oestrogens, their androgen precursors and upon the concentration of sex hormone binding globulin (SHBG) was investigated after 1 and 3 months and then every 3 months until progression of disease. A significant reduction in the serum concentration of oestrone (P < 0.0001) was obtained at all doses. Also, the serum concentration of oestrone sulphate was significantly reduced (P < 0.0001). However, after 1 month, the concentration was significantly different from pretreatment levels (P < 0.01) only at the 4 mg daily dose. A decline was also observed in the concentration of SHBG (P < 0.05), with a concomitant elevation of the percentage non-SHBG-bound oestradiol. The androgens, testosterone and dehydroepiandrosterone sulphate, were unaltered during treatment, while androstendione was significantly elevated at the 2 mg daily dose (P < 0.001).
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PMID:Sex hormone levels in postmenopausal women with advanced metastatic breast cancer treated with CGS 169 49A. 799 8

Breast cancer should be recognised as a systemic disease even at the stage when metastatic dissemination is not clinically evident. Chemotherapy and endocrine therapy, as systemic treatments require appropriate assessment in the context of multi-disciplinary treatment of breast cancer. Postoperative adjuvant therapy is being standardised based upon several randomized trials. The concept of dose-intensity was addressed through randomized trials. It was confirmed that dose-intensity correlated with higher response rates, but the effect of dose-intensive treatments on survival still needs to be established. High-dose chemotherapy along with autologous bone marrow support is being evaluated for its safety and efficacy. This strategy is also applied for postoperative adjuvant therapy of high-risk patients. Several new chemotherapeutic agents have evaluated clinically during the last years. Taxol, taxotare, navelbine, and anthracycline MX2 have been found to have efficacy against breast cancer. Antiestrogen analogs, new aromatase inhibitors, and LHRH analogs have introduced into clinics recently and they are changing the outfit of endocrine therapy. Appropriate combination of chemotherapy and endocrine therapy induced improved quality of life of metastatic breast cancer patients.
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PMID:[State of the art of drug therapy in breast cancer]. 827 39

The place of tamoxifen in the treatment of metastatic breast cancer is being challenged by the development of less estrogenic antiestrogens. New inhibitors of aromatase and estrone sulfatase have been reported. Anthrapyrazoles are new cytotoxic agents with high activity and low toxicity. Uncertainty about the optimal duration of chemotherapy continues. Methods to intensify chemotherapy, enabled by bone marrow support techniques, continue to be studied, but a routine role for this approach in palliative treatment of metastatic disease has not been established. Active specific immunotherapy appears to be practicable following identification of defined tumor-associated immunogens. Evidence for the ability of bisphosphonates to reduce morbidity from bone metastases continues to accumulate.
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PMID:Metastatic breast cancer. 830 49

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.
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PMID:The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer. 847 85

Hormonal manipulation is currently the mainstay of palliative care for metastatic breast cancer because it is well tolerated and produces significant responses in approximately one-third of unselected patients. Tamoxifen, a nonsteroidal antiestrogen, is currently considered first-line therapy. Second-line agents include progestins and aromatase inhibitors. New agents, such as the "pure" antiestrogens and the gonadotropin-releasing hormone (GnRH) agonists, are being tested. Other approaches for affecting the hormonal milieu are also under investigation, including combinations of hormonal agents, hormonal agents plus biologics, and hormonal agents plus antiproliferative agents. This review will address the basis for endocrine therapy and possible mechanisms of hormonal resistance, currently available agents and newer ones on the horizon, and areas of future interest.
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PMID:Current status of endocrine therapy for metastatic breast cancer. 856 27

Hormonal agents play a critical role in the palliation of advanced breast cancer, as well as adjuvant therapy to surgery and radiation in patients with primary breast cancer. Tamoxifen appears to be the therapy of choice for the initial treatment of metastatic breast cancer in both premenopausal and postmenopausal women, although some clinicians prefer oophorectomy or the use of luteinizing hormone releasing hormone analogues in premenopausal patients. Historically, second-line hormonal therapy for metastatic disease has been with a progestin; however, due to the troubling side effects of weight gain and dyspnea, progestins may soon be replaced by aromatase inhibitors. The development of new antiestrogens lacking estrogen-agonist activity for metastatic disease is in its earliest clinical developmental phases. For adjuvant therapy in postmenopausal women, there is conflicting evidence as to whether the combination of a hormonal agent (ie, tamoxifen) plus chemotherapy provides an advantage over hormonal therapy alone. In premenopausal women areas of active investigation include combination hormonal therapy (eg, tamoxifen plus luteinizing hormone releasing hormone analogues or oophorectomy) and combination chemohormonal therapy (concomitant v sequential). Tamoxifen had been associated with rare cases of thromboembolic events and secondary endometrial cancers. The etiology of these secondary cancers is unclear and controversial; however, the benefits of tamoxifen far outweigh the risks for both palliative and surgical adjuvant therapy. The success of tamoxifen in preventing cancer recurrence in the contralateral breast has led to clinical investigation of the drug for the chemoprevention of breast cancer in women at high risk for development of the disease. The role of tamoxifen for this indication remains to be determined following completion of the National Surgical Adjuvant Breast and Bowel Project trial in North America and additional trials in the United Kingdom and Italy.
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PMID:Hormonal approaches to breast cancer treatment and prevention: an overview. 882 59

Aromatase inhibitors are a new class of agents that are of considerable interest for potential use as palliative therapy for hormone-dependent metastatic breast cancer in postmenopausal women. In the postmenopausal or castrate female, the process of aromatization accounts for the majority of circulating, biologically active estrogens. This report presents a clinical perspective on some of the most recent information concerning the biology and pharmacology of the aromatase enzyme and highlights the development of newer aromatase inhibitors with important therapeutic potential. Clinical questions addressed include the selection of aromatase inhibitors, the selection of the most appropriate patients for therapy with these new agents, and the positioning of these new agents with respect to other forms of endocrine therapy for breast cancer. Finally, we shall consider areas for future investigation of possible new indications for these agents in clinical medicine.
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PMID:Aromatase inhibitors in clinical practice: current status and a look to the future. 882 63

Diagnosis and therapy of breast cancer are briefly reviewed for the general internist. He should know what triple diagnosis, breast-conserving surgery, radiotherapy and adjuvant systemic therapy involve. He should know when to perform a screening mammography, what follow-up examinations after breast cancer are indicated and what dangers loom in metastatic breast cancer. He should know of new therapeutic avenues such as bisphosphonates, new aromatase inhibitors, taxanes, and high-dose chemotherapy with stem cell support. Since advances in the treatment of breast cancer have been achieved mostly through randomized studies, a positive attitude toward such studies and a willingness to take part in them are desirable.
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PMID:[Breast carcinoma: state of the art]. 899 24

Anastrozole offers a new option for many postmenopausal women with metastatic breast cancer who no longer respond to antiestrogen therapy. It has a lower side effect profile for weight gain and peripheral edema and equivalent efficacy to the current second-line therapy, megestrol acetate, which may improve quality of life. Due to its selectivity and lack of clinically significant effects on cortisol metabolism, it does not have the toxicity problems of other aromatase inhibiting agents such as aminoglutethimide. Long-term studies are needed to adequately evaluate the impact of this degree of estrogen suppression on cardiovascular and bone mass risk factors [12]. Cost of therapy will certainly have an impact on the choice of second-line endocrine therapy in those with limited income sources and lack of prescription coverage. In summary, there is likely to be an increased use of nonsteroidal aromatase inhibitor agents for second-line hormonal therapy of breast cancer. Due to increased length of survival, these individuals will not be seen exclusively by oncologists; their care will be shared with their primary care provider [21]. Providers must have an understanding of these agents and their potential impact on the long-term health care of the individual in order to provide knowledgeable and comprehensive care.
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PMID:Role of new selective aromatase inhibitor in therapy for metastatic breast cancer in postmenopausal women. 907 23


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