Gynaecological Assessment of Postmenopausal Women with an Asymptomatic Thickened Endometrium While on Tamoxifen: Results from a Double Blind Randomized Controlled Trial Comparing Continuation of Tamoxifen and Anastrozole.
Authors: J. Van Ginderachter, J. Vlasselaer, E. De Jonge, P. Berteloot, H. Depypere, R. Van den Broecke, P. Neven, P. van Dam, D. Timmerman, C. Blomme, L. De Clercq, B. Van Calster, G. Vlaemynck, F. Amant, I. Vergote
Journal: Cancer Research (2009)

Abstract Background: The switch to adjuvant anastrozole/exemestane after 2-3 years of tamoxifen improves breast cancer outcome. Prior to this knowledge, we designed a multicentre randomised placebo-controlled study, to evaluate uterine and quality of life (QoL) issues comparing those switching to anastrozole and those continuing on tamoxifen in patients with a thickened endometrium after 2-3 years of tamoxifen treatment. The study was prematurely closed when anastrozole/exemestane became reimbursed by our health authorities following publication of a survival benefit from the adjuvant switch strategy in this setting. We here report on all randomized patients.Patients and Methods: Patients were postmenopausal, asymptomatic with a double endometrial thickness (DET) on transvaginal ultrasound (TVUS) of more than 7 mm. They were randomized between 20mg tamoxifen and 1mg anastrozole during the rest of 5 years of endocrine treatment; tablets were unrecognizable for drug assignment. The study aimed at investigating the TVUS changes with a measurement at baseline, at year 1 and when completing the endocrine therapy unless there were QoL issues, progression or vaginal bleeding. The primary study-endpoint was the change in DET and uterine volume (UV). Secondary endpoints were differences in the occurrence of menopausal symptoms between groups. Longitudinal fixed-effects regression analysis methods were used to evaluate uterine changes and QoL scores over time. Age and BMI were used as covariates.Results: The study randomized 72 subjects (37 anastrozole and 35 tamoxifen) from 5 institutions. Mean age (range) was 60 years (43 – 77 years); demographics were comparable but patients randomized to anastrozole were more likely lymph node positive. Subjects on anastrozole had a significant decrease in mean change in DET and UV already after 1 year. Both primary endpoints did not change over time when continuing tamoxifen but between-group differences were significant (p-values &amp;lt; 0.001). The covariates did not influence the effect of medication. Eleven patients withdrew from the study (7 on anastrozole; 4 on tamoxifen, ns); 2 had disease progression (both on anastrozole), 1 (on tamoxifen) developed a hematologic cancer, 7 stopped because of side effects (5 on anastrozole and 2 on tamoxifen) and arthralgia being most frequently reported for early stopping (4 anastrozole and 1 tamoxifen). AEs/SAEs were observed in 54% and 11% of patients on anastrozole and in 51% and 17% of patients on tamoxifen (ns). Regarding QoL, vaginal dryness increased for patients on anastrozole but not for patients on tamoxifen (p=0.008). No different evolution of arthralgia between both groups is suggested, even though more anatrozole patients withdrew due to arthralgia problems. Vaginal bleeding was reported in 5 (3 on tamoxifen and 2 on anastrozole).Conclusion: Although the study was prematurely stopped, we were able to show a strong decrease in DET and UV in asymptomatic postmenopausal tamoxifen users with a thickened endometrium after 2-3 years of tamoxifen who change to anastrozole. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4093.