One of the largest breast-cancer prevention trials conducted to date reports good news for postmenopausal women at increased risk of the disease. Initial results of the Study of Tamoxifen and Raloxifene, or STAR, show the drug raloxifene, currently used to prevent and treat osteoporosis, works as well as tamoxifen in reducing breast-cancer risk for postmenopausal women — with fewer side effects.
"It is thrilling to have another choice for women who are at increased risk of breast cancer," said Joelle Machia, a nurse in the Clinical Research Division and program coordinator for STAR. "Raloxifene can provide the same risk-reduction benefit of tamoxifen but with much less toxicity and fewer side effects, thus offering women another viable alternative. This is another significant step in breast-cancer prevention."
STAR enrolled 19,747 postmenopausal women who were at increased risk of the disease. The Center recruited 282 of the 552 Washington women who enrolled in the study. Participants were randomly assigned to receive either 60 mg of raloxifene (Evista®) or 20 mg of tamoxifen (Nolvadex®) daily for five years.
The National Surgical Adjuvant Breast and Bowel Project (NSABP), a network of cancer research professionals coordinated the trial, which is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health.
Tamoxifen side effects
Both drugs reduced the risk of developing invasive breast cancer by about 50 percent. Among the 9,745 women in the raloxifene group, 167 developed invasive breast cancer, compared to 163 of 9,726 women in the tamoxifen group.
"In 1998, the landmark Breast Cancer Prevention Trial showed that tamoxifen, compared to placebo, could reduce the risk of invasive breast cancer in premenopausal and postmenopausal women by nearly 50 percent," said Dr. Norman Wolmark, NSABP chairman. "Today, we can tell you that for postmenopausal women at increased risk of breast cancer, raloxifene is just as effective, without some of the serious side effects known to occur with tamoxifen."
Women who were prospectively and randomly assigned to take raloxifene daily, and were followed for an average of about four years, had 36 percent fewer uterine cancers than the women who were assigned to take tamoxifen. Uterine cancers, especially endometrial cancers, are a rare but serious side effect of tamoxifen. More than half of the women who joined STAR had a hysterectomy and, therefore, were not at risk of uterine cancer. For those women with a uterus, 36 of 4,732 who were assigned to take tamoxifen developed uterine cancers (mainly endometrial cancer) compared to 23 of 4,712 women who were assigned to take raloxifene.
Benefits may outweigh risks
Both tamoxifen and raloxifene are known to increase a woman's risk of blood clots. In STAR, women in the raloxifene group had 29 percent fewer deep-vein thromboses (blood clots in a major vein) and pulmonary embolisms (blood clots in the lung) than women in the tamoxifen group. Specifically, 87 of 9,726 women in the tamoxifen group had a deep-vein thrombosis compared to 65 of 9,745 women taking raloxifene. In addition, 54 of 9,726 women taking tamoxifen developed pulmonary embolisms compared to 35 of 9,745 women taking raloxifene.
Women taking either drug had equivalent numbers of strokes, heart attacks and bone fractures. Both raloxifene and tamoxifen are known to protect bone health; it is estimated that half a million postmenopausal women are currently taking raloxifene by prescription to prevent or treat osteoporosis. Additionally, the initial results from STAR suggest that raloxifene does not increase the risk of developing a cataract, as tamoxifen does.
"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 Dr. Leslie Ford, associate director for clinical research in NCI'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 STAR researchers also tracked known menopausal side effects that occur with both drugs and monitored the participants' quality of life. The data show that side effects of both drugs were mild to moderate in severity, and quality of life was the same for both drugs.
Machia noted an exceptionally high compliance rate, higher than rates usually seen on treatment studies. "This reflects the commitment and dedication of our participants without whose contribution these results would not have been possible," she said. "It is exciting to see the study come to its fruition. It speaks to the women who participated — our heroes — who made this all possible. These study participants have made a significant contribution to advancing our understanding of breast-cancer prevention, which will have an impact for generations to come," she said.
Women who participated in STAR were postmenopausal, at least 35 years old and had a high risk for breast cancer. Most had a 3 percent to 4 percent risk of getting breast cancer over a five-year period, as determined by their age, family history of breast cancer, personal medical history, age at first menstrual period and age at first live birth. The average 50-year old Caucasian woman has a 1.3 percent risk of getting breast cancer during the same period. Before enrolling in the study, the women were instructed about the potential risks and benefits of tamoxifen and raloxifene and then were asked to sign an informed-consent document. The participating sites were mainly community-based investigators, thus giving women the opportunity to participate in research locally, Machia said.
Participants in STAR are now receiving information about which drug they were taking. Women assigned to raloxifene will continue to be provided with the drug until they have completed five years of treatment. Those women assigned to tamoxifen can choose to continue taking tamoxifen or to receive raloxifene to complete their five years of treatment.
Principal investigator for the trial is Dr. Richard Clarfeld, a Center affiliate investigator and breast surgeon at Overlake Medical Center in Bellevue. STAR staff from the Center's Puget Sound Oncology Consortium include: Nancy Knudsen, program administrator; Heather Hughes, recruitment coordinator; and Barbara Deppe, program assistant.
For Q&A related to the STAR results, visit www.cancer.gov/newscenter/pressreleases/STARresultsQandA and for tools used to calculate a woman's risk of breast cancer, see www.cancer.gov/bcrisktool or www.breastcancerprevention.com.