This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de Jong, P. C. Articles by Blankenstein, R. A. Search for Related Content PubMed PubMed Citation Articles by de Jong, P. C. Articles by Blankenstein, R. A.

Inhibition of Breast Cancer Tissue Aromatase Activity and Estrogen Concentrations by the Third-Generation Aromatase Inhibitor Vorozole

Departments of Internal Medicine and Endocrinology, University Hospital Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands [P. C. d. J., J. v. d. V., I. M-S., G. H. D., J. H. H. T., M. A. B.]; Department of Internal Medicine, Hospital Diakonessenhuis Utrecht, 3582 KE Utrecht, the Netherlands [J. W. R. N.]; and Department of Internal Medicine, St. Antonius Hospital, 3435 CM Nieuwegein, the Netherlands [P. H. T. J. S.]

In about one-third of advanced breast cancers, estrogen deprivation causes tumor regression. Estrogen concentrations in tumor tissue seem to depend largely on local production. The aromatase enzyme complex is thought to be the key enzyme in this respect. In the present study, the effect of the new third-generation nonsteroidal aromatase inhibitor vorozole (Rivizor) on tumor tissue aromatase activity and estrogen concentrations was evaluated. During 7 days preceding mastectomy, 11 postmenopausal breast cancer patients were treated with 2.5 mg of vorozole once daily. Eight patients could be evaluated. Intratumoral aromatase activity and estrone and estradiol levels were measured and compared to the values of nine untreated postmenopausal breast cancer patients. In treated patients, median tissue aromatase activity was 89% lower than that in controls (P < 0.001). Similarly, median tissue estrone and estradiol concentrations were 64 and 80% lower, respectively, in treated patients (P = 0.001 and P < 0.05, respectively). These results support the hypothesis that depleting the tumor of estrogens, thus impairing estrogenic stimulation, is an important mechanism in the antitumor activity of aromatase inhibitors.

¹ To whom requests for reprints should be addressed, at P. O. Box 85500, 3508 GA Utrecht, the Netherlands.

Received 2/10/97. Accepted 4/20/97.

This article has been cited by other articles:

				E. R. Simpson, M. Misso, K. N. Hewitt, R. A. Hill, W. C. Boon, M. E. Jones, A. Kovacic, J. Zhou, and C. D. Clyne Estrogen--the Good, the Bad, and the Unexpected Endocr. Rev., May 1, 2005; 26(3): 322 - 330. [Full Text] [PDF]

				E. R. Simpson and M. Dowsett Aromatase and Its Inhibitors: Significance for Breast Cancer Therapy Recent Prog. Horm. Res., January 1, 2002; 57(1): 317 - 338. [Abstract] [Full Text] [PDF]

				E. R. Simpson and S. R. Davis Minireview: Aromatase and the Regulation of Estrogen Biosynthesis--Some New Perspectives Endocrinology, November 1, 2001; 142(11): 4589 - 4594. [Abstract] [Full Text] [PDF]

				J. Geisler, S. Detre, H. Berntsen, L. Ottestad, B. Lindtjørn, M. Dowsett, and P. E. Lønning Influence of Neoadjuvant Anastrozole (Arimidex) on Intratumoral Estrogen Levels and Proliferation Markers in Patients with Locally Advanced Breast Cancer Clin. Cancer Res., May 1, 2001; 7(5): 1230 - 1236. [Abstract] [Full Text]

				R. Clarke, F. Leonessa, J. N. Welch, and T. C. Skaar Cellular and Molecular Pharmacology of Antiestrogen Action and Resistance Pharmacol. Rev., March 1, 2001; 53(1): 25 - 72. [Abstract] [Full Text] [PDF]

				K. P. Nephew, E. Osborne, R. A. Lubet, C. J. Grubbs, and S. A. Khan Effects of Oral Administration of Tamoxifen, Toremifene, Dehydroepiandrosterone, and Vorozole on Uterine Histomorphology in the Rat Experimental Biology and Medicine, March 1, 2000; 223(3): 288 - 294. [Abstract] [Full Text]

				P. E. Goss, E. P. Winer, I. F. Tannock, and L. H. Schwartz on behalf of the North American Vorozole Randomized Phase III Trial Comparing the New Potent and Selective Third-Generation Aromatase Inhibitor Vorozole With Megestrol Acetate in Postmenopausal Advanced Breast Cancer Patients J. Clin. Oncol., January 1, 1999; 17(1): 52 - 52. [Abstract] [Full Text] [PDF]

				H. Sasano and N. Harada Intratumoral Aromatase in Human Breast, Endometrial, and Ovarian Malignancies Endocr. Rev., October 1, 1998; 19(5): 593 - 607. [Abstract] [Full Text]