Clinical Question: What are the relative effects of raloxifene (Evista) and tamoxifen (Nolvadex) on reducing the risk of developing invasive breast cancer?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: The investigators identified post-menopausal women, 35 years or older, with at least a five-year predicted breast cancer risk of 1.66 percent on the Gail model. A total of 19,747 consenting women (mean age = 58.5 years) met inclusion criteria. More than 93 percent of participants were white. Eligible women randomly received (concealed allocation) tamoxifen (20 mg per day) or raloxifene (60 mg per day) for a maximum of five years. Follow-up occurred for more than 94 percent of women for a mean of 3.9 years. The authors do not specifically state whether individuals assessing outcomes remained blinded to treatment group assignment.

Using intention-to-treat analysis, there were no significant differences between the two groups in the risk of invasive or noninvasive breast cancer, uterine cancer, other invasive cancers, ischemic heart disease events, stroke, osteoporotic fractures, or all-cause mortality. Thromboembolic events and cataracts occurred significantly less often in the raloxifene group. A related study in the same issue (Land SR, et al. Patient-reported symptoms and quality of life during treatments with tamoxifen or raloxifene for breast cancer prevention: the NSABP Study of Tamoxifen and Raloxifene [STAR] P-2 trial. JAMA 2006;295:2742–51) reported no significant differences between the treatment groups in physical health, mental health, or depression, but the tamoxifen group reported better sexual function.

Bottom Line: Tamoxifen and raloxifene are similarly effective for reducing the risk of invasive breast cancer in postmenopausal women. Although women taking tamoxifen are at an increased risk of thromboembolic events and cataracts, they report improved sexual function compared with women taking raloxifene. All-cause mortality and overall quality of life were similar in both treatment groups. (Level of Evidence: 1b–)