Aromatase inhibition for breast cancer treatment.

While the first generation aromatase inhibitor aminoglutethimide and second- and third generation inhibitors like formestane and fadrozole all have been found to inhibit in vivo aromatization by 85-93%, the novel aromatase inhibitors letrozole and arimidex inhibit in vivo aromatization by 97-99%. However, we do not know whether these drugs cause a higher response rate or a longer duration of remission compared with less potent aromatase inhibitors. Lack of cross-resistance to steroidal and non-steroidal aromatase inhibitors suggests that these drugs may have partially different mechanisms of action, probably by influencing the intratumour aromatase enzyme. Recent studies have shown that breast cancer cells may adapt to alterations in oestrogen concentration in vitro by increasing their sensitivity. The observation that patients suffering relapse following castration, hypophysectomy or adrenalectomy may respond to treatment with aromatase inhibitors suggests that similar mechanisms could be responsible for acquired resistance to oestrogen deprivation.