INHIBITION OF BREAST-CANCER TISSUE AROMATASE-ACTIVITY AND ESTROGEN CONCENTRATIONS BY THE 3RD-GENERATION AROMATASE INHIBITOR VOROZOLE

In about one-third of advanced breast cancers, estrogen deprivation ca uses tumor regression, Estrogen concentrations in tumor tissue seem to depend largely on local production, The aromatase enzyme complex is t hought to be the key enzyme in this respect. In the present study, the effect of the new third-generation nonsteroidal aromatase inhibitor v orozole (Rivizor) on tumor tissue aromatase activity and estrogen conc entrations was evaluated, During 7 days preceding mastectomy, 11 postm enopausal breast cancer patients were treated with 2.5 mg of vorozole once daily, Eight patients could be evaluated, Intratumoral aromatase activity and estrone and estradiol levels were measured and compared t o the values of nine untreated postmenopausal breast cancer patients, In treated patients, median tissue aromatase activity was 89% lower th an that in controls (P < 0.001), Similarly, median tissue estrone and estradiol concentrations were 64 and 80% lower, respectively, in treat ed patients (P = 0.001 and P < 0.05, respectively), These results supp ort the hypothesis that depleting the tumor of estrogens, thus impairi ng estrogenic stimulation, is an important mechanism in the antitumor activity of aromatase inhibitors.