Tamoxifen and Raloxifene Equally Effective in Preventing Invasive Breast Cancer, But Differences Seen for Non-Invasive Breast Cancer and Side Effects

Findings from the Study of Tamoxifen and Raloxifene (STAR) trial, one of the largest breast cancer prevention clinical trials ever conducted, show that tamoxifen (Nolvadex) and raloxifene (Evista) both reduce the risk of invasive breast cancer (cancer that has spread into the surrounding breast tissue) by about 50% in women at high risk for the disease. The study also found that raloxifene was not as effective as tamoxifen in lowering the number of noninvasive breast cancers. However, tamoxifen was associated with more uterine cancers and blood clots than raloxifene. A second analysis found no significant difference in the women's overall quality of life when comparing the two drugs.

Tamoxifen is approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of breast cancer recurrence (return) and to lower the risk of developing breast cancer for premenopausal and postmenopausal women at high risk for this disease. Raloxifene is approved by the FDA to prevent osteoporosis (thinning of the bones), and has been shown in previous clinical trials to reduce breast cancer risk in postmenopausal women. The STAR trial is the first head-to-head comparison of these drugs.

The STAR trial was conducted at more than 500 sites in the United States and Canada by the National Surgical Adjuvant Breast and Bowel Project (NSABP). It included 19,747 postmenopausal women at increased risk of breast cancer. The women received either raloxifene or tamoxifen once daily for five years, starting in July 1999.

After four years, the researchers found a similar number of invasive breast cancers in women taking tamoxifen (163 cases), compared with the women taking raloxifene (167 cases). However, fewer noninvasive breast cancers, such as ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS), were reported in the women receiving tamoxifen (57 cases) than the women receiving raloxifene (81 cases). Untreated DCIS may become an invasive cancer in some women.

The number of uterine cancers was greater among women on tamoxifen (36) than in those who received raloxifene (23). Although both drugs are known to increase the risk of blood clots, the risk was 29% lower in the raloxifene group compared with the tamoxifen group. Researchers found no significant difference between the groups with regard to the incidence of heart problems, stroke, bone fracture, or death.

"These findings show that raloxifene represents an effective alternative for breast cancer prevention in postmenopausal women at high risk for this disease, with fewer side effects than tamoxifen," said D. Lawrence Wickerham, MD, Associate Chairman of the NSABP, and lead author of the study. He noted that the decision to choose one drug over another is based on a woman's medical history, and that women with certain cardiovascular problems or uncontrolled diabetes may not be able to take raloxifene. Raloxifene has not been evaluated in premenopausal women at high risk for breast cancer, Dr. Wickerham added, but they may be candidates for tamoxifen.

In a second analysis, researchers compared quality of life among 973 women taking tamoxifen and 1,010 women taking raloxifene. The women were followed for about five years, and researchers found no difference between the two groups in overall physical or mental health and depression.

Researchers evaluated the severity of the side effects in all 19,747 women. Most side effects reported by the women were mild, but there were differences between the drugs. For example, the women taking tamoxifen were more likely to report hot flashes (mainly seen in women under age 60), vaginal bleeding and discharge, bladder control problems, and leg cramps, whereas women taking raloxifene were more likely to report joint pain, pain during sexual intercourse, and vaginal dryness.

"We now have two drugs that are effective for reducing breast cancer risk in women at high risk for this disease, neither of which significantly impairs overall quality of life," said Patricia Ganz, MD, Professor at the UCLA Schools of Medicine and Public Health and Director of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center in Los Angeles, who directed the quality of life assessment in the STAR trial.

What This Means For Patients

Both tamoxifen and raloxifene lower the risk of invasive breast cancer for women at high risk. Patients and their doctors should consider the patient's medical history, current symptoms, and personal preferences when selecting the appropriate drug.