Hairloss Study Abstract: Clinical use of aromatase inhibitors in the treatment of breast cancers.

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Title: Clinical use of aromatase inhibitors in the treatment of breast cancers.
Title Abreviation: J Cell Biochem Suppl		Date of Pub: 1993
Author: Manni A;
Issue/Part/Supplement: -HEADING-	Volume Issue: 17G		Pagination: 242-6
MESH Headings: Aminoglutethimide (TU); Animal; Aromatase (AI); Breast Neoplasms (DT); Fadrozole (TU); Female; Human; Nitriles (TU); Rats; Triazoles (TU); -RN-;
Journal Title Code: K8K	Publication Type: JOURNAL ARTICLE
Date of Entry: 940721N	Entry Month: 9409
Country: UNITED STATES	Index Priority: 2
Language: Eng	Unique Identifier: 94276620
Unique Identifier: 94276620	ISSN: 0733-1959
Abstract: Estrogens are the major hormones supporting the growth of human breast cancer. Aromatization of androgen precursors in peripheral tissues, including the breast cancer itself, is the major source of estrogens in postmenopausal women. Therefore, inhibition of the aromatase enzyme offers an effective means of inducing regression of hormone-responsive breast cancer. Aminoglutethimide, the first and most widely tested aromatase inhibitor, suppresses estrogen production to the level of adrenalectomy and exerts an anti-tumor action comparable to other standard endocrine therapies such as tamoxifen. However, conventional doses of the drug (1000 mg daily) cause moderate toxicity and inhibit other critical cytochrome P-450 steroidogenic enzymes, thus requiring concomitant glucocorticoid administration. New non-steroidal, competitive aromatase inhibitors with greater selectivity and less toxicity are being developed. The second generation compound, fadrazole (CGS 16949), lowers estrogen production to a degree similar to aminoglutethimide (50-80%), but at much lower doses (approximately 2 mg daily) and is associated with minimal toxicity. Although not totally specific, this drug is sufficiently selective not to require simultaneous cortisol replacement. CGS 16949 has been shown to possess significant anti-tumor action in pilot studies and is currently being tested in Phase III trials. Recently, a third generation inhibitor, CGS 20267, has been found to have virtually complete selectivity for the aromatase enzyme. Furthermore, this drug suppresses estrogen biosynthesis to a greater extent (approximately 90%) than previously observed with other aromatase inhibitors. Such enhanced activity may lead to a superior anti-tumor action, and may extend the use of this drug to a variety of other conditions where optimal suppression of estrogen biosynthesis is desired.
Abstract By: Author
Address: Milton S. Hershey Medical Center, Department of Medicine, Pennsylvania State University, Hershey 17033.
Number of References: 15
Last Revision Date: 940808