In a randomized trial 1 a total of 7 145 women aged 35-70 years and at increased risk of breast cancer were assigned to receive either tamoxifen (20 mg/day) or placebo for 5 years. The primary outcome measure was the incidence of breast cancer, but side effects were also investigated. After a median follow-up of 96 months after randomization, 142/3579 breast cancers were diagnosed in the tamoxifen group and 195/3575 in the placebo group (4.97 versus 6.82 per 1000 woman-years, respectively; RR 0.73, 95% CI 0.58 to 0.91). The prophylactic effect of tamoxifen was fairly constant for the entire follow-up period for up to 10 years after randomization. Side effects in the tamoxifen group decreased after the active treatment period. For example, deep-vein thrombosis and pulmonary embolism were higher in the tamoxifen arm than in the placebo arm during active treatment (52 vs. 23 cases, RR 2.26, 95% CI 1.36 to 3.87) but not after tamoxifen was stopped (16 vs. 14 cases, RR 1.14, 95% CI 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% CI 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% CI = 0.50 to 0.87).
A technology assessment report 2 on tamoxifen and raloxifene in chemoprevention of breast cancer was abstracted in the Health Technology Assessment Database. There is strong, direct evidence that tamoxifen reduces by approximately half the incidence of invasive and noninvasive breast cancer in pre- and postmenopausal women at high risk for breast cancer.
The largest chemoprevention trial, BCPT 3, enrolled 13,388 women ages 35 and older who had an estimated 5-year risk of breast cancer of at least 1.66 percent. In the placebo group, 175 women were diagnosed with invasive breast cancer and 89 in the tamoxifen group (RR, 0.51; 95 percent CI, 0.39-0.66). The absolute risk reduction was 21.4 cases per 1,000 women over 5 years (NNT 47). There were 69 cases of noninvasive breast cancer in the placebo group and 35 in the tamoxifen group (RR, 0.50; p <0.002). The absolute risk reduction was 8.2 cases per 1,000 women (NNT, 122). The relative risk reduction was similar across all age groups and all risk levels. The drug was effective only against estrogen receptor-positive tumors. The drug is associated with an increased risk of venous thromboembolic disease (deep vein thrombosis and pulmonary embolism) and also with an increased risk of endometrial cancer. The balance between benefits and harms varies among subgroups of women, depending on age, predicted risk of breast cancer, and hysterectomy status.
Primary/Secondary Keywords