Endometrial effects of exemestane compared to tamoxifen within the TEAM trial: Results of a prospective randomized study

Abstract

572 Background: A prospective open label randomized multicenter substudy was performed in the German TEAM Trial Group to compare the effects of the irreversible aromatase antagonist Exemestane (EXE) and the ER agonist/antagonist Tamoxifen (TAM) on the endometrium during adjuvant treatment for postmenopausal estrogen receptor positive breast cancer. Methods: Transvaginal Ultrasound Scans (TVS) were performed at baseline, 6 and 12 months of treatment if no proliferation >5mm was present, and in 3 months intervals if endometrial thickness exceeded 5mm. Intent-to-treat analysis was performed based on 158 patients. Primary endpoint was the time interval from randomization to the earliest occurrence of endometrial hyperplasia > 10mm. Secondary endpoints were the time from randomization to endometrial hyperplasia > 5mm and the time interval from randomization to vaginal bleeding. Analysis of Time to Event Curves was performed by Kaplan-Meier method, analysis of differences between treatments by two-sided Logrank test and Cox Proportional Hazards. Differences in frequency were compared by Fisher‘s Exact Test. Results: 65 patients were available for analysis in the TAM arm, 78 in the EXE arm. Both groups were comparable regarding age, height, tumor grade,and stage. Median follow-up was 727 (EXE) and 526 days (TAM). In this time period, there were no (EXE) vs. 11 (TAM) cases of endometrial hyperplasia >10mm (p<0.0001), 11 (EXE) vs. 34 (TAM) patients with hyperplasia >5mm (p< 0.006). In total, endometrial hyperplasia was observed 11 times in the EXE arm vs. 45 times in the TAM arm (p<0.0001). Time to endometrial hyperplasia was significantly longer in the EXE group (p<0.0001); HR was 0.160 indicating an 84% risk reduction of hyperplasia in the EXE group. Increase in endometrial thickness from baseline to 6mo. was 2.94mm (EXE) vs. 5.41mm(TAM), from baseline to 12 mo 2.64mm vs. 6.0 mm respectively (p<0.0006). Only 1 patient underwent histological sampling in the EXE group (no hyperplasia) vs. 18 in the TAM subset. Conclusions: In a TEAM subprotocol, irreversible inactivation of aromatase by EXE resulted in significantly less endometrial proliferation than TAM during adjuvant therapy of receptor positive postmenopausal breast cancer. No significant financial relationships to disclose.