Long-Term Results of Tamoxifen Prophylaxis for Breast Cancer—96-Month Follow-up of the Randomized IBIS-I Trial

Background Initial results from the first International Breast Cancer Intervention Study (IBIS-I) found that tamoxifen reduced the risk of invasive estrogen receptor (ER)-positive tumors by 31% in women at increased risk for breast cancer, but most of the follow-up at this time was during the active treatment phase. We report an updated analysis of IBIS-I that focuses on the period after active treatment was completed, a time for which little evidence from other trials is available.

Methods A total of 7145 women who were aged 35-70 years and at increased risk of breast cancer were randomly assigned to receive either tamoxifen (20 mg/day) or placebo for 5 years. The primary outcome measure was the incidence of breast cancer (including ductal carcinoma in situ), but side effects were also investigated. Relative risks were computed as the ratio of incidence rates. All statistical tests were two-sided.

Results After a median follow-up of 96 months after randomization, 142 breast cancers were diagnosed in the 3579 women in the tamoxifen group and 195 in the 3575 women in the placebo group (4.97 versus 6.82 per 1000 woman-years, respectively; risk ratio [RR] = 0.73, 95% confidence interval [CI] = 0.58 to 0.91, P = .004). The prophylactic effect of tamoxifen was fairly constant for the entire follow-up period, and no diminution of benefit was observed for up to 10 years after randomization. However, side effects in the tamoxifen group were much lower after completion of the active treatment period than during active treatment. For example, deep-vein thrombosis and pulmonary embolism were statistically significantly higher in the tamoxifen arm than in the placebo arm during active treatment (52 versus 23 cases, RR = 2.26, 95% Cl = 1.36 to 3.87) but not after tamoxifen was stopped (16 versus 14 cases, RR = 1.14, 95% Cl = 0.52 to 2.53). The two arms did not differ in the risk of ER-negative invasive tumors (35 in each arm, RR = 1.00, 95% Cl = 0.61 to 1.65) across the entire follow-up period, but the risk of ER-positive invasive breast cancer was 34% lower in the tamoxifen arm (87 versus 132 cases, RR = 0.66, 95% Cl = 0.50 to 0.87).

Conclusions The risk-reducing effect of tamoxifen appears to persist for at least 10 years, but most side effects of tamoxifen do not continue after the 5-year treatment period.