Effect of Tamoxifen or Anastrozole on Steroid Sulfatase Activity and Serum Androgen Concentrations in Postmenopausal Women with Breast Cancer

被引:0
作者
Stanway, S. J. [1 ]
Palmieri, C. [2 ]
Stanczyk, F. Z. [3 ]
Folkerd, E. J. [4 ]
Dowsett, M. [4 ]
Ward, R. [2 ]
Coombes, R. C. [2 ]
Reed, M. J. [1 ]
Purohit, A. [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sect Investigat Med, Oncol Drug Discovery Grp, London W12 0NN, England
[2] Hammersmith Hosp, Dept Oncol, Canc Res UK Labs, London W12 0NN, England
[3] Univ So Calif, Keck Sch Med, Womens & Childrens Hosp, Reprod Endocrine Res Lab, Los Angeles, CA 90033 USA
[4] Royal Marsden Hosp, Dept Biochem, London SW3 6JJ, England
关键词
Aromatase inhibitors; anti-estrogens; breast cancer; steroid sulfatase; tamoxifen; anastrozole; postmenopausal women; IN-VIVO INHIBITION; ESTRONE SULFATASE; AROMATASE INHIBITORS; 17-BETA-HYDROXYSTEROID DEHYDROGENASE; CELL-PROLIFERATION; ESTRONE-3-O-SULFAMATE; ESTRADIOL; ANDROSTENEDIONE; STIMULATION; SUPPRESSION;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: In postmenopausal women estrogens can be formed by the aromatase pathway, which gives rise to estrone, and the steroid sulfatase (STS) route which can result in the formation of estrogens and androstenediol, a steroid with potent estrogenic properties. Aromatase inhibitors, such as anastrozole, are now in clinical use whereas STS inhibitors, such as STX64, are still undergoing clinical evaluation. STX64 was recently shown to block STS activity and reduce serum androstenediol concentrations in postmenopausal women with breast cancer. In contrast, little is known about the effects of aromatase inhibitors or anti-estrogens on STS activity or serum androgen levels. Patients and Methods: Study 1: Blood was collected from ten postmenopausal women with breast cancer before and after two-week treatment with anastrozole and serum concentrations of androstenediol and other androgens and estrogens were assessed. Study 2: Blood samples were collected from 15 breast cancer patients before and after four-week treatment with anastrozole and 10 patients before and after four-week treatment with tamoxifen. Blood was used to assess STS activity in peripheral blood lymphocytes (PBLs) and serum dehydroepiandrosterone sulfate and dehydroepiandrosterone levels. Results: Neither anastrozole nor tamoxifen had any significant effect on STS activity as measured in PBLs. Anastrozole did not affect serum androstenediol concentrations. Conclusion: Anastrozole and tamoxifen did not inhibit STS activity and serum androstenediol concentrations were not reduced by aromatase inhibition. As androstenediol has estrogenic properties, it is possible that the combination of an aromatase inhibitor and STS inhibitor may give a therapeutic advantage over the use of either agent alone.
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页码:1367 / 1372
页数:6
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