Background: Tamoxifen treatment results in a doubling of the risk of endometrial cancer after 1-2 years of treatment and a quadrupling after 5 years. Anastrozole, a third-generation aromatase inhibitor, with superior efficacy to tamoxifen, may also offer tolerability benefits in terms of effects on the endometrium. Methods and results: A sub-protocol of the ATAC trial compared the incidence/type of intrauterine changes following treatment with these agents in a subgroup of patients (n = 285) from the main trial. After 2 years anastrozole treatment, endometrial thickness remained ≤ 5 mm (baseline: 3.0 mm); in patients receiving tamoxifen, endometrial thickness increased by 3.2 mm to 7.0 mm, with a similar trend in the combination group. At baseline, 26/285 patients (9.1%) had endometrial abnormalities, most commonly polyps. After 2 years the number of endometrial abnormalities appeared lower with anastrozole treatment compared with tamoxifen although these differences were not statistically significant (odds ratio: 0.44; 95% confidence interval 0.146, 1.314; P = 0.14). Most abnormalities occurred within the first year of treatment (anastrozole: 4/6; tamoxifen: 7/10; combination: 10/16; total: 21/32). Fewer patients in the anastrozole group (1.4%) required medical intervention (tamoxifen 12.5%; combination 13.6%). Conclusions: Fewer endometrial abnormalities occurred during 2 years treatment with anastrozole compared with tamoxifen although statistical significance was not reached in this sub-protocol analysis.

Anastrozole, ATAC, Breast cancer, Endometrial pathology, Tamoxifen,
Human Reproduction
Department of Medical Oncology

Duffy, S, Jackson, T.L, Lansdown, M, Philips, K, Wells, M, Pollard, S, … Klijn, J.G.M. (2006). The ATAC ('Arimidex', tamoxifen, alone or in combination) adjuvant breast cancer trial: First results of the endometrial sub-protocol following 2 years of treatment. Human Reproduction, 21(2), 545–553. doi:10.1093/humrep/dei322