PHARMACOLOGICAL PROFILES OF EXEMESTANE AND FORMESTANE, STEROIDAL AROMATASE INHIBITORS USED FOR TREATMENT OF POSTMENOPAUSAL BREAST-CANCER

Steroidal aromatase inhibitors like formestane and exemestane are usef ul drugs for endocrine treatment of postmenopausal breast cancer. In a ddition, these drugs should be considered valuable probes to explore t he biology of breast cancer with particular emphasis on possible relat ions between the degree of estrogen suppression and clinical efficacy and the possible role of intratumor estrogen synthesis. The fact that steroidal and non-steroidal aromatase inhibitors bind to different par ts of the aromatase enzyme suggests these drugs may act in concert agg ravating plasma estrogen suppression. Thus, use of a steroidal and a n on-steroidal aromatase inhibitors in concert may be one way to improve breast cancer treatment and may also provide important information to a better understanding of the dose-response relationship between estr ogen suppression and clinical effects. Further, the finding that patie nts progressing on non-steroidal aromatase inhibitors may respond to f ormestane as well as exemestane suggests these drugs may have differen tial effects, probably on the aromatization in the tumor tissue. Furth er studies are warranted to explore the influence of steroidal and non -steroidal aromatase inhibitors on intratumor aromatase activity and i ntratumor estrogen concentrations and to correlate these findings to i ntratumor drug concentrations. The findings that steroidal aromatase i nhibitors map have clinical effects in patients progressing on treatme nt with the non-steroidal aromatase inhibitor aminoglutethimide is cha llenging, and suggest further studies to evaluate possible benefits of using different novel aromatase inhibitors in concert or sequence.