Tamoxifen reduces the risk of breast cancer by a third over four years in healthy women at high risk of developing the disease, a major international study has shown.
But the investigators consider that the increased risk of thromboembolism and endometrial cancers from the drug means that longer term follow up is needed before a clear recommendation can be made on its use in primary breast cancer prevention.
Results from the international breast cancer intervention study (IBIS 1), published last week, found a significant excess of deaths from all causes in the tamoxifen group (25 v 11; P=0.028) and a non-significant increase in endometrial cancer (11 v 5; P=0.2).
But it showed that prophylactic tamoxifen (20 mg a day), compared with placebo, reduced the risk of breast cancer by 32% (95% confidence interval 8% to 50%; P=0.013) in healthy, high risk women after a median follow up of 50 months. At this time, 25% of women had completed five years of treatment (the duration of treatment that was chosen to be tested) and a further 47% were still having treatment. The rest stopped taking tamoxifen before five years were up.
Only 69 breast cancers occurred in the 3578 women randomised to tamoxifen compared with 101 in the 3566 given matching placebo .
The study included women aged 35-70 years who had risk factors for breast cancer, most commonly (62%) two or more first degree or second degree relatives with breast cancer.
The reduction in breast cancer with tamoxifen followed conflicting results seen in previous studies. A North American trial showed a 50% reduction in breast cancer incidence, but little or no reduction was seen in two previous European trials.
The new study confirmed, however, that tamoxifen was associated with more than a doubling in risk of thromboembolic events (odds ratio 2.5 (1.5 to 4.4; P=0.001)), with even greater risk after surgery. The investigators therefore recommended that prophylactic use of tamoxifen was contraindicated in women at high risk of thromboembolic disease and temporary cessation of the drug should be considered during and after major surgery. 