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Original Article

Anastrozole (Arimidex®), a New Aromatase Inhibitor for Advanced Breast Cancer: Mechanism of Action and Role in Management

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Pages 385-390 | Published online: 11 Jun 2009
 

Abstract

Breast cancer is the most common cancer in American women, and is estimated to be the cause of 46,000 deaths per year (1-3). The incidence of breast cancer increases with age, with breast cancer more common in menopausal and postmenopausal women than in younger women (4). Approximately one-third of all breast cancers are hormone dependent; because estrogen is the primary steroidal mitogen, hormonal manipulation has proven to be a successful modality in these cases (3,5,6). Tumors likely to respond to endocrine therapy can be identified through the presence of estrogen and progesterone receptors, with positive response rates as high as 60% in patients with estrogen receptor (ER)-positive tumors and 75% in cases in which both estrogen and progesterone receptors have been detected (6,7). Postmenopausal women are more likely than younger women to have breast tumors positive for both estrogen and progesterone receptors; in addition, the absolute concentration of these receptors may also be higher in tumors in post- menopausal women (8). A relatively new strategy for the blockade of estrogen synthesis in the management of advanced breast cancer in postmenopausal women is aro- matase inhibition with the selective, nonsteroidal inhibitor anastrozole (Arimidex®) (9-15). Aromatase inhibition presents a number of advantages over other endocrine therapies, including a well-defined mechanism of action, specific inhibition of estrogen synthesis, a lack of estrogenic effects, and lack of cross-resistance with antiestrogens (5). When compared with other aromatase inhibitors (e.g., aminoglutethimide, formestane, fadrozole), anastrozole has a number of advantages, including high potency, high specificity for the aromatase enzyme, a favorable safety profile, a convenient mode of administration, and no requirement for corticosteroid replacement therapy (9-12,15,16).

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