Description of Evidence
An update of the BCPT results after 7 years of follow-up demonstrates results similar to those in the initial report. Follow-up was more complete for the tamoxifen group than for the placebo group because of a greater drop-out rate among women in the placebo group after early termination of the study. In addition, women who received a placebo were given the option of taking tamoxifen or participating in the Study of Tamoxifen and Raloxifene (STAR), and 32% did so. Breast cancer rates decreased among women in the placebo group from year 6 to year 7 of follow-up. A statistically significant RR of 43% for invasive breast cancer persisted at follow-up despite the addition of women to the placebo arm. The rate of invasive breast cancer among women in the placebo group was 6.29 per 1,000 women versus 3.59 per 1,000 women for women in the tamoxifen group, for a risk reduction of 0.27%. Benefits and risks of tamoxifen were not significantly different from those in the original report, with persistent benefit of reductions in fracture and persistent risks of endometrial cancer, thrombosis, and cataract surgery. No overall mortality benefit was observed after 7 years of follow-up (RR = 1.10; 95% CI, 0.85-1.43).
Other trials of tamoxifen for primary prevention of breast cancer have been completed.[81,82,83] Initial analyses from two smaller trials, one in the United Kingdom (U.K.)  and one primarily in Italy, showed no protective effect, perhaps because of differences between target populations and study designs and those in the U.S. study. The U.K. study focused on 2,471 women at increased breast cancer risk because of their family history of breast and/or ovarian cancer; about 36% of participants were from families that had a greater than 80% chance of carrying a breast cancer susceptibility gene. After a median follow-up of nearly 6 years, no protective effect of tamoxifen was detected (RR = 1.06). Subsequent follow-up shows that at a median of 13 years, there was a statistically nonsignificant reduction in breast cancer risk in the tamoxifen arm compared with the placebo arm (HR = 0.78; 95% CI, 0.58-1.04). However, risk of ER-positive breast cancer was significantly reduced in the treatment arm (HR = 0.61; 95% CI, 0.43-0.86), an effect noted predominantly in the posttreatment period. The Italian study focused on 5,408 women who had undergone hysterectomy and who were described as "low-to-normal risk" women. At the initial report, after a median follow-up of nearly 4 years, no protective effect of tamoxifen was observed. Longer follow-up and subgroup analysis in the Italian trial found a protective effect of tamoxifen among women at high risk for hormone receptor-positive breast cancer (RR = 0.24; 95% CI, 0.10-0.59) and among women who were taking HT during the trial (RR = 0.43; 95% CI, 0.20-0.95).[85,86]