Current perspectives on aromatase inhibitors in breast cancer.
OBJECTIVE
One way to deprive hormone-dependent breast cancer of estrogen is to prevent its synthesis. This is achievable by inhibiting the aromatase cytochrome P-450 (P-450arom) enzyme complex responsible for the ultimate step in estrogen production. A new generation of specific and selective aromatase inhibitors is currently under investigation. The purpose of this review is to outline the preclinical test systems for screening these inhibitors, to summarize the preclinical and clinical data published to date, and to discuss the future application of these inhibitors in the management of breast cancer.


CONCLUSIONS
Disadvantages to the use of earlier inhibitors are described. In vitro and in vivo experiments that reflect the potency and selectivity of new inhibitors are highlighted. From preliminary clinical trials, these inhibitors appear to have excellent pharmacokinetic profiles and produce few side effects when administered orally. Activity against postmenopausal metastatic breast cancer has been demonstrated for the agents reviewed. They are all now in phase III testing to determine their relative efficacy in this setting. Their application in combination with both hormone therapy and chemotherapy, in premenopausal metastatic disease, and in the adjuvant setting in both premenopausal and postmenopausal women remains to be defined.
Department of Hematology/Oncology, Toronto Hospital--General Division, Canada.
P E
PE
Goss
K M
KM
Gwyn
D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000201:enzymology / Q000628:therapy*; D004354:Drug Screening Assays, Antitumor; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D013329:Structure-Activity Relationship
D047072:Aromatase Inhibitors; D004967:Estrogens; D001141:Aromatase