[4055] Anastrozole is associated with a lower risk of endometrial abnormalities than tamoxifen: first report of the ATAC trial endometrial sub-protocol at 6 years follow-up.

Duffy S, on Behalf of the ATAC Trialists' Group.. St Jamess University Hospital, Leeds, United Kingdom

Background: Tamoxifen treatment increases the risk of endometrial cancer. Anastrozole, a highly selective aromatase inhibitor with superior efficacy and overall tolerability relative to tamoxifen, may also have important benefits in terms of its impact on the endometrium. This sub-protocol of the randomized, double-blind, multicenter Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial (ISRCTN18233230) was designed prospectively to examine the effects of tamoxifen and anastrozole on the uterus when used as primary adjuvant therapy.
Material and Methods: The ATAC trial compared adjuvant hormonal therapy with anastrozole (1 mg/day) or tamoxifen (20 mg/day) alone or in combination for 5 years. Patients (n=271) who were included in the endometrial sub-protocol were postmenopausal women with invasive, operable breast cancer who enrolled in the main ATAC trial and had not received prior tamoxifen, had no previous or planned hysterectomy, and no previous endometrial ablation at baseline. Endometrial abnormalities were assessed using transvaginal ultrasonography (TVS), hysteroscopy, and pipelle sampling at baseline and after 1, 2, and 6 years of treatment. Endometrial thickness was also assessed with TVS. The primary objective was to compare the incidence of abnormal endometrial histology results in patients receiving anastrozole vs tamoxifen.
Results: At a mean follow-up of 6 years, anastrozole treatment was associated with a lower number of endometrial abnormalities (most commonly polyp formation) than tamoxifen treatment (27% vs 44%; odds ratio 0.52; 95% confidence intervals 0.20, 1.32; p=0.17). The rate of endometrial abnormalities occurring was highest during the first year of treatment. In patients treated with anastrozole, median endometrial thickness at 6 years was the same as at baseline (3.0 mm), whereas median endometrial thickness increased from 3.0 mm at baseline to 5.0 mm at 5 years in patients treated with tamoxifen. In tamoxifen-treated patients, endometrial thickening continued until cessation of treatment.
Discussion: After 6 years follow-up, there was a trend to fewer endometrial abnormalities with anastrozole treatment than with tamoxifen, which was consistent with the trend at 1 and 2 years. Unlike tamoxifen, anastrozole does not have a stimulatory effect on endometrium and did not lead to an increase in endometrial thickness. The results of the endometrial sub-protocol are consistent with findings of the main ATAC trial, which showed that anastrozole is more efficacious, generally better tolerated, associated with fewer gynecological adverse events (including endometrial cancer) than tamoxifen, and that the majority of endometrial events occur early in treatment.

Saturday, December 16, 2006 7:00 AM

Poster Session IV: Treatment: Endocrine Therapy (7:00 AM-9:00 AM)