Raloxifene as Good as Tamoxifen to Prevent Breast Cancer

Both Drugs Cut Risk in Half for High-Risk Women

The bone drug raloxifene (Evista) is just as good as tamoxifen in preventing invasive breast cancer in high-risk women, federal health officials announced today. Both drugs cut the risk of breast cancer in half.

That could give women another option to safeguard their health, experts said, if the Food and Drug Administration approves raloxifene for breast cancer prevention. But which drug a woman chooses will depend on her particular situation, since the 2 medications are slightly different.

"Although no drugs are without side effects, tamoxifen and raloxifene are vital options for women who are at increased risk of breast cancer and want to take action," said Leslie Ford, MD, associate director for clinical research at the National Cancer Institute's Division of Cancer Prevention. "For many women, raloxifene's benefits will outweigh its risks in a way that tamoxifen's benefits do not."

Ford joined other researchers in an afternoon telephone conference to release the first findings from the Study of Tamoxifen and Raloxifene, known as the STAR trial. It involved nearly 20,000 women who had a higher-than-average risk for breast cancer because of factors like their age, family history of the disease, personal medical history, age at which they began menstruating, or the age they had their first child. The women had to be at least 35 years old and already past menopause. Nearly half of the women in the study were 50-59 years old, and another 41% were 60 or older.

Half of the women were randomly assigned to take raloxifene, and half were assigned to tamoxifen. They took the drugs every day for 5 years. Both drugs are pills.

Differences in Uterine, Noninvasive Breast Cancers
Tamoxifen and raloxifene lowered the risk of invasive breast cancer by about the same amount, the researchers said. Previous studies have shown tamoxifen reduces risk by about 50%. The women on both drugs had similar risks for strokes and heart attacks, and both drugs seemed to reduce the risk of bone breaks by about the same extent.

But there were also some important differences.
Women on raloxifene had 36% fewer uterine cancersr than women on tamoxifen, which is known to increase the risk of these cancers. Both drugs are known to increase the risk of blood clots in major veins and the lungs, but women on raloxifene had 29% fewer of either type than women on tamoxifen. Both of those results were just shy of statistical significance. In addition, raloxifene did not appear to raise the risk of cataracts, which tamoxifen does appear to do. That difference was statistically significant.

However, tamoxifen protected women better from non-invasive breast cancers. Tamoxifen is known to reduce the risk of developing lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) by about half. Although similar numbers of women were taking each drug, 57 women on tamoxifen developed LCIS or DCIS, while 81 women on raloxifene did.

"The outcome of the study is not as clear cut as we might have hoped for," said Len Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society. "It will take some time for experts to review the data to determine which of the two treatments is preferable."

Although LCIS and DCIS are not life-threatening, they do require treatment and women who develop either condition (and particularly DCIS) have a higher risk of developing breast cancer later.

"It's an important consideration," Lichtenfeld said.

But Lawrence Wickerham, MD, one of the researchers involved with the study, said, "We feel raloxifene is the winner of this study, given its equivalence to tamoxifen in prevention of invasive breast cancer with fewer life-threatening side effects."

Wickerham is protocol officer for the STAR trial and associate chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP), which ran the study.

Researchers plan to release more data from the trial at a large cancer conference in June.

Raloxifene Not Yet Approved for Breast Cancer Prevention
Raloxifene is not yet approved by the Food and Drug Administration (FDA) as a breast cancer prevention drug. But about half a million women past menopause already take the drug to prevent or treat osteoporosis. The researchers said they expect raloxifene's manufacturer, Eli Lilly and Co., to ask the FDA to approve it for breast cancer prevention.

Tamoxifen is most commonly used as a treatment for women with breast cancer whose tumors have estrogen receptors. It was approved to prevent breast cancer in high-risk women in 1998. The FDA has specific criteria for figuring out if a woman is eligible to take tamoxifen for this purpose. It is estimated that about 15% of all women over age 35 would be eligible to use tamoxifen in this way, but not every woman who could take it for breast cancer prevention does.

The side effects have frightened many women away from using tamoxifen for this purpose, noted Norman Wolmark, MD, NSABP chairman.

"Women who are considering breast cancer prevention therapy should talk with their health care provider," the NCI said in a question-and-answer document about the new study findings. That's because each woman's personal health history is important in determining whether this type of drug is right for her.

Lichtenfeld echoed that advice.
"For now it will be very important for women an increased risk of breast cancer to make an informed decision with the advice of their physician as to which approach is best for them," he said. "It is also important to note that while both drugs can prevent many breast cancers, neither has been shown to reduce the risk of death due to the disease."