PLASMA ESTROGEN SUPPRESSION WITH AROMATASE INHIBITORS EVALUATED BY A NOVEL, SENSITIVE ASSAY FOR ESTRONE SULFATE

Aromatase inhibition is a well-defined treatment option for postmenopa usal breast cancer. Although several aromatase inhibitors such as amin oglutethimide, formestane and fadrozole have been found to inhibit tit vivo aromatization by >85%, previous studies reported plasma estrogen levels to be sustained at approximately 20-50% of their control level during treatment with these drugs. The discrepancy could be due to la ck of sensitivity or non-specific crossreactions in the radioimmunoass ay (RIA) methods. Mean plasma levels of estrone (E-1) and estradiol (E -2) in postmenopausal women are approximately 80 and 20 pmol/l, respec tively; on the contrary, mean plasma levels of the estrogen conjugate estrone sulphate (E1S) are approximately 4-500 pmol/l. Most RIA method s for plasma E-2 and El measurements have sensitivity limits in the ra nge of 2-3 and 7-10 pmol/l, respectively; accordingly, the suppression of plasma estrogens by more than 80-90% will produce hormone values b elow the sensitivity Limit of the method in many patients. Recently, w e developed a new method to determine plasma E1S. This assay has a sen sitivity limit of 2.7 pmol/l. In theory, this method may allow the det ermination of plasma E1S levels suppressed to less than 2% of control values in the majority of patients. Using this method, we found differ ent aromatase inhibitors such as formestane, aminoglutethimide, formes tane and aminoglutethimide administered in concert or anastrozole to s uppress plasma E1S levels down to 24, 13, 7 and 4%, respectively. The suppression of plasma E1S evaluated with this method thus approaches t he percentage aromatase inhibition measured with tracer studies. (C) 1 997 Elsevier Science Ltd.