Raloxifene Prevents Breast Cancer in Women at Increased Risk

The osteoporosis drug raloxifene (Evista) is just as good as tamoxifen in preventing invasive breast cancer in postmenopausal women at increased breast cancer risk and has fewer toxicities, according to initial findings from the Study of Tamoxifen and Raloxifene, known as the STAR trial. However, unlike tamoxifen, raloxifene does not protect against lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS).

Researchers involved in the STAR trial hailed the results as good news for women concerned about their potential for developing breast cancer.

“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.”

The National Cancer Institute (NCI) sponsored the trial, which was run by the National Surgical Adjuvant Breast and Bowel Project (NSABP). It involved nearly 20,000 women who had an increased risk for breast cancer because of factors like age, family history of the disease, personal medical history of breast biopsies (especially those showing atypical hyperplasia), age at which they began menstruating, or the age they had their first child. The tool they used to calculate risk is posted on NCI's Web site at http://www.cancer.gov/bcrisktool/ and through NSABP at http://www.breastcancerprevention.org/.

The women had to be at least 35 years old and already past menopause. Nearly half of the women in the study were 50 to 59 years old, and another 41% were 60 or older. Participants were randomly assigned to take raloxifene (60 mg) or tamoxifen (20 mg) every day for 5 years.

STAR researchers first presented their results in a teleconference in April, and released additional data at the 2006 annual meeting of the American Society for Clinical Oncology in June. The results had not yet been published in a peer-reviewed journal when CA went to press.

Tamoxifen and raloxifene lowered the risk of invasive breast cancer by about the same amount, the researchers said in their initial reports. Previous studies have shown tamoxifen reduces risk by about 50%. For those study participants who did develop breast cancer, there were no differences in the sizes of the primary tumor, axillary lymph node status, or estrogen receptor status. The women on both drugs had similar risks for strokes and heart attacks, and both drugs seemed to reduce the risk of fractures by about the same extent.

But there were also some important differences.

Women on raloxifene had fewer uterine cancers than women on tamoxifen, which is known to increase the risk of these cancers. Of the 4,732 women with a uterus who were assigned to tamoxifen, 36 developed uterine cancer (primarily endometrial cancer), compared with 23 of the 4,712 women on raloxifene, a 36% reduction.

Women on raloxifene also had fewer blood clots than women on tamoxifen, though both drugs are known to increase the risk of thromboembolic events. Of the 9,726 women on tamoxifen, 87 developed deep vein thromboses, and 54 developed pulmonary emboli. For the 9,745 women on raloxifene, the figures were 65 and 35, respectively, a 29% overall reduction.

Raloxifene had a statistically significant effect on cataracts, reducing incidence compared with tamoxifen.

But raloxifene did not protect women from LCIS and DCIS as well as did tamoxifen, which is known to reduce the risk of these conditions 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 ACS. “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 invasive breast cancer later.

“It's an important consideration,” Lichtenfeld said.

Lawrence Wickerham, MD, Protocol Officer for the STAR trial and Associate Chairperson of the NSABP, 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.”

Raloxifene is not yet approved by the US Food and Drug Administration (FDA) as a breast cancer prevention drug. But about a half-million women past menopause already take the drug to prevent or treat osteoporosis. Raloxifene's manufacturer, Eli Lilly and Co., plans to ask the FDA to approve it for breast cancer risk reduction by the end of 2006.

Tamoxifen is most commonly used as a treatment for women with estrogen receptor-positive breast cancer. It was approved in 1998 for risk reduction in women at increased breast cancer risk. But the drug's side effects have frightened many women away from using tamoxifen for this purpose, noted Norman Wolmark, MD, NSABP chairperson.

Women who are interested in taking a drug for breast cancer prevention should consult their doctor about the risks and benefits, Lichtenfeld said.

“For now it will be very important for women at 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. 

Figure  .

Early results of the STAR trial show that raloxifene matches tamoxifen in reducing the risk of invasive breast cancer, with fewer toxicities.