CARDIAC AND VASCULAR MORBIDITY IN WOMEN RECEIVING ADJUVANT TAMOXIFEN FOR BREAST-CANCER IN A RANDOMIZED TRIAL

Objective-To determine any cardiac or vascular morbidity associated wi th long term treatment with tamoxifen given after mastectomy for prima ry breast cancer. Design-Cohort study using linkage between database o f a randomised trial and statistics of Scottish hospital inpatients to identify episodes of cardiac and vascular morbidity. Setting-NHS hosp itals in Scotland. Subjects-1312 women who had undergone mastectomy fo r breast cancer and who were randomised either to a treatment group to receive adjuvant tamoxifen or to a control group to be given tamoxife n only on first relapse of disease. Maximum duration of tamoxifen trea tment was 14 years. Total woman years of follow up were 9943. Main out come measures-Randomised and observational comparisons of risk (expres sed as hazard ratios) of myocardial infarction, other cardiac event, c erebrovascular disease, or thromboembolic event according to treatment allocated and between nonusers, former users, and current users of ta moxifen. Results-Use of tamoxifen was associated with lower rates of m yocardial infarction. Hazard ratio for women in control group was 1.92 (95% confidence interval 0.99 to 3.73) compared with women allocated to adjuvant treatment. The association was stronger for current use: h azard ratio for nonusers was 3.49 (1.52 to 8.03) compared with current users. Current users of tamoxifen, however, had higher rates of throm boembolic events: hazard ratio for non-users was 0.40 (0.18 to 0.90) c ompared with current users. Conclusions-Our results provide further ev idence that tamoxifen reduces the risk of myocardial infarction. Throm boembolic events should be carefully monitored in trials of tamoxifen, particularly those of prophylactic treatment, in which tamoxifen is g iven to healthy women.