Emerging role of aromatase inhibitors in the treatment of breast cancer.
The new generation of potent steroidal and nonsteroidal inhibitors of the enzyme aromatase act by decreasing estrogen production throughout the body in postmenopausal women. The most potent of these agents may also inhibit estrogen synthesis within metastatic breast cancer tissue. The newly developed, orally administered, nonsteroidal competitive inhibitors, such as anastrozole (Arimidex), letrozole (Femara), and vorozole (Rizivor), are a thousand times more potent inhibitors of aromatase than is aminoglutethimide. Furthermore, these agents are highly selective. In several large randomized trials, the new inhibitors produced similar response rates as megestrol acetate (160 mg/d) in postmenopausal women with hormone-dependent breast cancer, but showed a trend toward improved response duration and survival. They also produced less weight gain and fewer cardiovascular and thromboembolic side effects. In addition, letrozole proved superior to aminoglutethimide in another randomized trial. Both anastrozole (1.0 mg/d) and letrozole (2.5 mg/d) have now been approved as second-line treatment for hormone-dependent breast cancer in postmenopausal women in whom disease has progressed following tamoxifen treatment. Either drug should replace the routine use of megestrol acetate in this setting. Ongoing clinical studies are comparing anastrozole and letrozole to antiestrogens as first-line endocrine therapy for metastatic breast cancer. Other trials will study the possible roles of these compounds as adjuvant therapy and chemoprevention for breast cancer.
Harvey
H A
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Section of Hematology-Oncology, Hershey Medical Center, Penn State Geissinger Health Systems, Hershey, Pennsylvania, USA.
D000368:Aged; D000616:Aminoglutethimide / Q000627:therapeutic use; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006801:Humans; D000077289:Letrozole; D019290:Megestrol Acetate / Q000627:therapeutic use; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000201:enzymology*; D009570:Nitriles / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D014230:Triazoles / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D000616:Aminoglutethimide; C060523:vorozole; D000077384:Anastrozole; D000077289:Letrozole; D019290:Megestrol Acetate