The long-awaited results of the largest breast cancer chemoprevention trial ever conducted provide what its leaders say is excellent news: Regular use of the anti-osteoporosis drug raloxifene (Evista) works just as well as tamoxifen at reducing breast cancer risk in postmenopausal women at high risk, but appears less likely to cause some of the potentially dangerous side effects seen with tamoxifen use.

"These results demonstrate that raloxifene represents an effective alternative for postmenopausal women at increased risk of breast cancer," said Dr. D. L. Wickerham, associate chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP), which coordinated the Study of Tamoxifen and Raloxifene (STAR).

The STAR results, added Dr. Leslie Ford, associate director for clinical research in NCI's Division of Cancer Prevention, "have immediate implications for how women view their breast cancer risk and what they can do about it. They will make breast cancer prevention more of a reality for many women."

More than 19,000 postmenopausal women participated in the NCI-sponsored STAR clinical trial. Participants were randomly assigned to receive 60 mg of raloxifene or 20 mg of tamoxifen every day for 5 years. All of the women in the trial were considered at increased risk for breast cancer based on several criteria, including family history and their personal medical history.

The rates of invasive breast cancers were nearly equivalent in participants on raloxifene and those on tamoxifen: 167 breast cancers among the 9,745 women on raloxifene compared with 163 cases among the 9,726 women taking tamoxifen.

The STAR trial may very well change the landscape of breast cancer chemoprevention, Dr. Ford said. Despite the 50-percent reduction in breast cancer risk among women who took tamoxifen in the Breast Cancer Prevention Trial (BCPT), its adoption rate as a chemopreventive outside of clinical trials has been sluggish. The slow uptake has been mostly attributed to concerns about the side effects seen in the BCPT participants on tamoxifen, including an increased risk of uterine cancers, primarily endometrial cancer, and vascular side effects such as a pulmonary embolism (a blood clot in the lungs) and deep-vein thrombosis (blood clots in major veins).

In STAR, however, there was a 36-percent reduction in uterine cancers in women on raloxifene compared with those on tamoxifen. (More than half the women who joined STAR had had a hysterectomy and therefore were not at risk for uterine cancer.) While the reduction did not achieve statistical significance, Dr. Wickerham notes, numerous studies comparing raloxifene to placebo have shown no increase in endometrial cancers.

In addition, women in the raloxifene group had almost 30 percent fewer deep-vein thromboses and pulmonary embolisms than women in the tamoxifen group.

Because tamoxifen has long been used for cancer treatment, Dr. Ford notes, that may have raised flags in many clinicians' minds about using it to prevent cancer.

"I think primary care physicians, gynecologists, and internists were somewhat uncomfortable with tamoxifen, despite its extensive safety profile," she says. "But raloxifene has been used by gynecologists and family practice physicians for preventing osteoporosis, so they may be more comfortable prescribing it."

Raloxifene, which, like tamoxifen, is a selective estrogen receptor modulator, or SERM, has not been approved by the FDA for use in breast cancer chemoprevention. Yesterday, however, the drug's manufacturer, Eli Lilly, issued a statement saying it would request the agency's approval to market raloxifene for the prevention of invasive breast cancer in postmenopausal women.

"Tamoxifen is still an incredibly effective drug and it's the only drug currently approved for breast cancer chemoprevention, and that includes in premenopausal women," says Dr. Wickerham. "The discussion about whether women should switch to raloxifene needs to be between each patient and her doctor."

By Carmen Phillips