Tamoxifen and Retinal Vaso–Occlusive Disease

Abstract

Abstract: : Purpose: Tamoxifen is an estrogen receptor modulator used in the treatment of breast cancer, both as a valuable adjuvant and as a chemopreventive agent. Concerns have been raised about its potential complications to the eye and a major question is whether or not the previously demonstrated increased risk for systemic thromboembolic disease would be similarly observed for retinal vessel occlusive disease (RVOD). The purpose of the present study was to evaluate the adverse effects data from the NSABP–sponsored Breast Cancer Prevention Trial (BCPT; P–1) for the prevalence of RVOD in both the treatment and control groups. Methods: A total of 13,204 subjects were included in the trial. Participants were randomly assigned to the double–masked treatment groups of placebo (6608 women) or tamoxifen (6596 women). The number of women experiencing RVOD were tabulated and average annual incidence rates per 1000 person years were calculated by treatment group. The relative risk and 95% confidence intervals were determined. Overall, the placebo and tamoxifen–treatment groups were very similar with respect to the frequency of conventional systemic and ocular risk factors for thrombosis, such as diabetes, smoking, hypertension and glaucoma. Results: The different forms of RVOD were too infrequent for individual statistical analyses. In aggregate, these lesions showed no statistical evidence (p=0.32) of an increased prevalence in the tamoxifen–treated cohort (11 cases) as compared to that of the control group (8 cases). The average annual rates per 1000 of RVOD were 0.29 and 0.40, respectively. The relative risk of a vaso–occlusive event associated with tamoxifen was 1.37 with a 95% confidence interval of 0.50 to 3.93. Conclusion: The low rate of RVOD in the tamoxifen group should provide some reassurance to those taking this therapy, since it appears to be lower than that associated with other known conventional risk factors. Given that the prior evidence regarding ocular effects of tamoxifen has been predominantly from case reports, one must view any efforts to establish a causal relationship of tamoxifen with RVOD with a great deal of caution. The evaluation of the effects of any drug requires a sufficient sample size and a masked controlled study in order to unambiguously establish its safety and complication profile.

Keywords: drug toxicity/drug effects • vascular occlusion/vascular occlusive disease • clinical (human) or epidemiologic studies: risk factor assessment