Aromatase inhibitors were first reported in the early 1970s and have been used to treat
breast cancer since that time. Until recently, essentially the only agent available in this class was
aminoglutethimide, a nonspecific inhibitor with multiple adverse effects and drug interactions. Selective and potent
aromatase inhibitors are now available (
formestane,
exemestane,
fadrozole,
anastrozole and
letrozole), and we review the risks and benefits of these agents in order to assist clinicians in making treatment decisions.
Formestane is an
injectable steroidal
aromatase inhibitor with significant activity against metastatic
breast cancer. It has been shown to have similar efficacy and superior tolerability compared with
megestrol, and is similar to
tamoxifen in the metastatic setting.
Exemestane is an oral steroidal
aromatase inhibitor. It has been shown to be effective third-line
therapy after
tamoxifen and
megestrol in postmenopausal patients with metastatic
breast cancer. All the nonsteroidal (
imidazole/
triazole)
aromatase inhibitors are orally available.
Fadrozole has similar activity to
megestrol and
tamoxifen in the setting of
metastasis, but has been shown in phase II trials to inhibit
cortisol and
aldosterone production.
Anastrozole and
letrozole have similar toxicity profiles. Compared with
megestrol,
anastrozole improves overall survival and has superior tolerability.
Letrozole is superior to
megestrol and
aminoglutethimide in terms of overall survival and time to progression, and is also better tolerated. Although there is a strong rationale for using these agents in the treatment of
breast cancer, the information presently available is insufficient to recommend any one agent over another. Direct comparative studies are lacking, and comparing agents across studies is limited by many biases and may not be valid.
Formestane is only available as an injection and
exemestane is not commercially available in many countries, making these agents more difficult to recommend over the other 3 agents.
Fadrozole is less potent and less selective in inhibiting
aromatase than
letrozole. The efficacies of
fadrozole,
megestrol and
tamoxifen appear to be similar; however, comparative data show no advantage of
fadrozole over
letrozole.
Anastrozole and
letrozole are generally considered to be similar agents. The clinical future of the selective
aromatase inhibitors is promising, and these agents may change the way postmenopausal
breast cancer is treated at all stages of the disease.