Results from the MORE clinical trial (Multiple Outcomes of Raloxifene Evaluation) add to previous research which shows that the drug raloxifene (brand name, Evista) may significantly reduce the risk of invasive breast cancer in post-menopausal women. Raloxifene is currently approved by the U.S. Food and Drug Administration (FDA) to help prevent or treat osteoporosis, a degenerative bone disease that affects roughly one in two women over age 50. Raloxifene is similar in composition to the drug tamoxifen (brand name, Nolvadex), which is FDA approved to help prevent and treat breast cancer. While further research on raloxifene is necessary, data suggests that raloxifene may be as effective as tamoxifen in preventing breast cancer without the small increased risk of endometrial cancer (cancer of the uterine lining) that is associated with tamoxifen.

The MORE trial was conducted by Eli Lilly and Company, the maker of raloxifene. In the trial, 2,557 women were given 60 milligrams (mg) per day of raloxifene; 2,572 women were given 120 mg per day of raloxifene; and 2,576 women were given a placebo (an inactive pill). Because raloxifene is used to treat osteoporosis, the women in the study were not necessarily at high risk of developing breast cancer. All of the women were given routine screening mammograms.

After four years of treatment, lead researcher Jane Cauley, MD and her colleagues found that women who took raloxifene were significantly less likely to develop either invasive breast cancer or estrogen-receptor positive invasive breast cancer than the women who were given the placebo. Invasive breast cancer occurs when cancer cells break through the duct and lobular wall and invade the surrounding fatty and connective tissues of the breast. Estrogen-receptor positive breast cancer is the most common type of breast cancer in post-menopausal women. This type of cancer is dependent on the hormone estrogen for survival and may respond well to treatments that target or deprive estrogen from its estrogen receptors (such as tamoxifen).

In the MORE trial, the most common side effects of raloxifene were hot flashes and leg cramps. There was also an increased risk of deep vein thrombosis (blood clots in the deep veins of the legs) among the women who took raloxifene. Other side effects included flu syndrome, endometrial cavity fluid, and peripheral edema (swelling). Dr. Cauley and her colleagues did not observe an increased risk of endometrial cancer in the women who used raloxifene compared to the women who took a placebo. By contrast, tamoxifen has been linked to a small risk of endometrial cancer (approximately 2 out of 1000 women on tamoxifen develop endometrial cancer).

While the results of the MORE trial are promising, further data is still needed before raloxifene can obtain FDA approval to help prevent breast cancer. Previous results of the MORE trial (published in the Journal of the American Medical Association) showed that three years of treatment with raloxifene can help reduce the risk of invasive breast cancer by approximately 76%. A separate study published in the Journal of the National Cancer Institute also found that raloxifene does not increase breast density, a non-cancerous condition that can make breast cancers more difficult to detect with mammography.

Several additional clinical trials on raloxifene are currently underway. In particular, the STAR trial (Study of Tamoxifen and Raloxifene) is enrolling 22,000 post-menopausal women at high risk of breast cancer to study the long-term safety and effectiveness of both tamoxifen and raloxifene. More than 500 centers in the United States, Canada, and Puerto Rico are enrolling women in STAR, which is being conducted by researchers from the University of Pittsburgh Medical Center’s National Adjuvant Breast and Bowel Project (NSABP). Eli Lilly and Company is also conducting the RUTH trial (Raloxifene Use for the Heart), which will investigate whether raloxifene can help prevent heart attacks and other serious cardiac events as well as invasive breast cancer in women at high risk for coronary artery disease and heart attack.

The American Cancer Society recommends the following guidelines to help detect breast cancer early, when the chances for successful treatment and survival are the greatest:

• All women between 20 and 39 years of age should practice monthly breast self-exams and have a physician performed clinical breast exam at least every three years.
• All women 40 years of age and older should have annual screening mammograms, practice monthly breast self-exams, and have yearly clinical breast exams. The clinical breast exam should be conducted close to and preferably before the scheduled mammogram.

In addition, women with a strong family history of breast cancer or those who test positive for the BRCA1 (breast cancer gene 1) or BRCA2 (breast cancer gene 2) mutations may want to talk to their physicians about beginning annual screening mammograms earlier than age 40, as early as age 25 in some cases.

Currently women at high risk of breast cancer may wish to discuss the following options with their physicians:

• Close monitoring with regular clinical exams, regular screening mammography, and monthly breast self-exams
• Taking tamoxifen for a period of five years
• Enrolling in the STAR clinical trial, which is comparing tamoxifen and raloxifene (must meet eligibility requirements)
• Prophylactic bilateral mastectomy (preventive removal of both breasts), usually followed by breast reconstruction (for women at very high risk of breast cancer)

Additional Resources and References

• The February 13, 2001 Eli Lilly and Company news release, "Final Data from Landmark MORE Study Show Evista Continues to Reduce Breast Cancer Risk Through Four Years," is available at http://newsroom.lilly.com/news/story.cfm?id=756
• The latest MORE trial study results will be published in the February 26, 2001 issue of Breast Cancer Research and Treatment. The journal is available online at http://www.wkap.nl/jrnltoc.htm/0167-6806
• The study, "The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women," is published in the June 16, 1999 issue of the Journal of the American Medical Association (Vol. 281, No. 23). The study is available online at http://jama.ama-assn.org/issues/v281n23/abs/joc90196.html
• The study, ""Digitized Mammography: a Clinical Trial of Postmenopausal Women Randomly Assigned to Receive Raloxifene, Estrogen, or Placebo," is published in the January 3, 2001 issue of the Journal of the National Cancer Institute. An abstract of the study is available online at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
  cmd=retrieve&db=pubmed&list_uids=11136842&dopt=Abstract
• To learn more about raloxifene, please visit http://www.imaginis.com/osteoporosis/osteo_treatment.asp#raloxifene
• For information on tamoxifen or the side effects of tamoxifen, please visit http://www.imaginis.com/breasthealth/tamoxifen.asp and http://www.imaginis.com/breasthealth/side_effects.asp
• For information on the STAR trial (Study of Tamoxifen and Raloxifene), please visit http://www.imaginis.com/breasthealth/star/
• To learn more about the guidelines for early breast cancer detection, please visit http://www.imaginis.com/breasthealth/earlydetection.asp

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