Influence of neoadjuvant anastrozole (Arimidex) on intratumoral estrogen levels and proliferation markers in patients with locally advanced breast cancer

Anastrozole (Arimidex) is a novel, selective, and potent aromatase inhibito r used for the treatment of postmenopausal breast cancer. The drug has been shown to inhibit in vivo aromatization by 96-97% and to suppress plasma es trogen levels by 84-94%. However, the effects of anastrozole on intratumora l estrogen levels have not been studied. Here we report the effects of neoa djuvant treatment with anastrozole on intratumoral levels of estrone (E,), estradiol (E-2), and estrone sulfate (E,S), measured by a highly sensitive RIA following a multistep purification procedure involving high-pressure li quid chromatography, Tumor tissue was obtained prior to treatment and after 15 weeks an therapy with anastrozole (I mg once daily) from 12 postmenopau sal women with locally advanced breast cancer (T-3-T-4 and/or N-2). Pretrea tment tissue levels of E-2, E-1, and E1S were 217.9 (69.8-679.9), 173.6 (83 .9-358.9), and 80.7 (31.4-207.3) fmol/g tissue (geometric mean values with 95% confidence interval, respectively), Treatment with anastrozole suppress ed tissue E-2, E-1, and E1S levels by 89.0% (73.2-95.5%), 83.4% (63.2-92.5% ), and 72.9% (47.3-86.1%), respectively, compared with baseline levels, wit h no significant difference between responders and nonresponders, Plasma Le vels of E,, E-1, and E1S were suppressed by 86.1, 83.9, and 94.2%, respecti vely. Anastrozole caused a decrease in the immunoexpression of the prolifer ation markers Ki67 and pS2 in all of the patients, with a trend for a more profound suppression in those achieving an objective response. The mean per centage of apoptotic cells was found to be decreased in responders and incr eased in nonresponders after 15 weeks of anastrozole therapy. Our results r eveal anastrozole to cause a significant suppression of tissue estrogen lev els and to influence the biology of primary estrogen receptor-positive brea st cancers in postmenopausal women.