Use of aromatase inhibitors in breast carcinoma

Aromatase, a cytochrome P-450 enzyme that catalyzes the conversion of androgens to estrogens, is the major mechanism of estrogen synthesis in the post-menopausal woman. We review some of the recent scientific advances which shed light on the biologic significance, physiology, expression and regulati...

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Veröffentlicht in:Endocrine-related cancer 1999-03, Vol.6 (1), p.75-92
Hauptverfasser: Santen, R J, Harvey, H A
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description Aromatase, a cytochrome P-450 enzyme that catalyzes the conversion of androgens to estrogens, is the major mechanism of estrogen synthesis in the post-menopausal woman. We review some of the recent scientific advances which shed light on the biologic significance, physiology, expression and regulation of aromatase in breast tissue. Inhibition of aromatase, the terminal step in estrogen biosynthesis, provides a way of treating hormone-dependent breast cancer in older patients. Aminoglutethimide was the first widely used aromatase inhibitor but had several clinical drawbacks. Newer agents are considerably more selective, more potent, less toxic and easier to use in the clinical setting. This article reviews the clinical data supporting the use of the potent, oral competitive aromatase inhibitors anastrozole, letrozole and vorozole and the irreversible inhibitors 4-OH androstenedione and exemestane. The more potent compounds inhibit both peripheral and intra-tumoral aromatase. We discuss the evidence supporting the notion that aromatase inhibitors lack cross-resistance with antiestrogens and suggest that the newer, more potent compounds may have a particular application in breast cancer treatment in a setting of adaptive hypersensitivity to estrogens. Currently available aromatase inhibitors are safe and effective in the management of hormone-dependent breast cancer in post-menopausal women failing antiestrogen therapy and should now be used before progestational agents. There is abundant evidence to support testing these compounds as first-line hormonal therapy for metastatic breast cancer as well as part of adjuvant regimens in older patients and quite possibly in chemoprevention trials of breast cancer.
doi_str_mv 10.1677/erc.0.0060075
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control</topic><topic>Comparative Study</topic><topic>Drug Design</topic><topic>Drug Interactions</topic><topic>Drug Resistance, Neoplasm</topic><topic>Enzyme Inhibitors - classification</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Estrogens - biosynthesis</topic><topic>Female</topic><topic>Humans</topic><topic>Middle Aged</topic><topic>Neoplasm Proteins - antagonists &amp; inhibitors</topic><topic>Neoplasm Proteins - physiology</topic><topic>Neoplasms, Hormone-Dependent - drug therapy</topic><topic>Neoplasms, Hormone-Dependent - enzymology</topic><topic>Neoplasms, Hormone-Dependent - prevention &amp; control</topic><topic>Nitriles - adverse effects</topic><topic>Nitriles - pharmacology</topic><topic>Nitriles - therapeutic use</topic><topic>Postmenopause</topic><topic>Premenopause</topic><topic>Review</topic><topic>Tamoxifen - pharmacology</topic><topic>Tamoxifen - therapeutic use</topic><topic>Triazoles - adverse effects</topic><topic>Triazoles - pharmacology</topic><topic>Triazoles - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Santen, R J</creatorcontrib><creatorcontrib>Harvey, H A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Endocrine-related cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Santen, R J</au><au>Harvey, H A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Use of aromatase inhibitors in breast carcinoma</atitle><jtitle>Endocrine-related cancer</jtitle><addtitle>Endocr. 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This article reviews the clinical data supporting the use of the potent, oral competitive aromatase inhibitors anastrozole, letrozole and vorozole and the irreversible inhibitors 4-OH androstenedione and exemestane. The more potent compounds inhibit both peripheral and intra-tumoral aromatase. We discuss the evidence supporting the notion that aromatase inhibitors lack cross-resistance with antiestrogens and suggest that the newer, more potent compounds may have a particular application in breast cancer treatment in a setting of adaptive hypersensitivity to estrogens. Currently available aromatase inhibitors are safe and effective in the management of hormone-dependent breast cancer in post-menopausal women failing antiestrogen therapy and should now be used before progestational agents. 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subjects Adult
Aminoglutethimide - adverse effects
Aminoglutethimide - pharmacology
Aminoglutethimide - therapeutic use
Androstadienes - adverse effects
Androstadienes - pharmacology
Androstadienes - therapeutic use
Androstenedione - adverse effects
Androstenedione - analogs & derivatives
Androstenedione - pharmacology
Androstenedione - therapeutic use
Antineoplastic Agents, Hormonal - pharmacology
Antineoplastic Agents, Hormonal - therapeutic use
Aromatase - physiology
Aromatase Inhibitors
Breast Neoplasms - drug therapy
Breast Neoplasms - enzymology
Breast Neoplasms - prevention & control
Comparative Study
Drug Design
Drug Interactions
Drug Resistance, Neoplasm
Enzyme Inhibitors - classification
Enzyme Inhibitors - pharmacology
Enzyme Inhibitors - therapeutic use
Estrogens - biosynthesis
Female
Humans
Middle Aged
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - physiology
Neoplasms, Hormone-Dependent - drug therapy
Neoplasms, Hormone-Dependent - enzymology
Neoplasms, Hormone-Dependent - prevention & control
Nitriles - adverse effects
Nitriles - pharmacology
Nitriles - therapeutic use
Postmenopause
Premenopause
Review
Tamoxifen - pharmacology
Tamoxifen - therapeutic use
Triazoles - adverse effects
Triazoles - pharmacology
Triazoles - therapeutic use
title Use of aromatase inhibitors in breast carcinoma
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