Pilot Study of Daily Exemestane in Women with Endometrial Intraepithelial Neoplasia or Low-Grade Endometrial Cancer.

PURPOSE: To evaluate exemestane, an aromatase inhibitor, as a preventive intervention for endometrial cancer. EXPERIMENTAL DESIGN: This is a multicenter, single-arm, "window of opportunity" pilot study of exemestane (25 mg daily for 21-42 days) in postmenopausal individuals undergoing hysterectomy for endometrial intraepithelial neoplasia (EIN) or low-grade endometrial cancer. The primary objective is to determine the change in proliferation, measured by Ki-67 expression, in pre- and posttreatment endometrial tissue specimens. Secondary outcomes include measurement of circulating serum estradiol and progesterone levels, pathologic response, tissue biomarkers, safety, and adverse effects. RESULTS: Forty participants were accrued to the study. The mean body mass index was 40.3 (range, 22.8-60.5, SD = 9.8). Preoperative diagnoses included EIN (n = 11, 27.5%), grade 1 endometrial cancer (n = 26, 65%), and grade 2 endometrial cancer (n = 3, 7.5%). Median Ki-67 score decreased from 40.7% [IQR (33.9, 50.3)] at baseline to 18.1% [IQR (8.8, 31.8)] at surgery, representing a median absolute change from baseline of 20.4% [IQR (-29.9, -6.7), P < 0.001]. In a matched historic control cohort, participants also had a decrease in Ki-67 score with a median absolute change from baseline of -6.7% [IQR (-12.7, -1.3), P< 0.001]. However, the decrease in Ki-67 was greater in the study participants than the historic controls, with a median difference between the groups of -13.4% [IQR (-23.3, 6.9), P ≤ 0.01]. Both tissue estrogen receptor and progesterone receptor expression declined significantly with exemestane treatment (P < 0.001). However, serum estradiol levels did not change between baseline and after treatment (P = 0.16). CONCLUSIONS: In this pilot study, exemestane demonstrated antiproliferative effects in EIN and low-grade endometrial cancer. This agent warrants further evaluation for the prevention of endometrial cancer.