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.

Abstract

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 < 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.