By Abby Sinnott

Researchers at the University of California, San Francisco report that a novel osteoporosis prevention drug, called raloxifene, reduced the risk of invasive breast cancer in postmenopausal women with osteoporosis by 76 percent after forty months of treatment.

The final results of the Multiple Outcomes of Raloxifene Evaluation (MORE) trial are published in the June 16 issue of The Journal of the American Medical Association (JAMA).

“This is an exciting start because women who are concerned about breast cancer now have another alternative for reducing their risk of developing the disease and preventing osteoporosis at the same time,” says Steven R. Cummings, MD, UCSF professor of medicine and epidemiology and lead author of the study.  “If raloxifene’s benefits continue over a longer period of time, treatment with the drug may be a way of substantially reducing a woman’s lifetime risk of breast cancer.”

The overall 76 percent reduction in the incidence of breast cancer is due to a 90 percent reduction in the risk of estrogen-receptor positive breast cancer (ER+) and 0.88 reduction in the risk of estrogen-receptor negative (ER-) breast cancer among study participants who received raloxifene, Cummings says. ER+ breast cancer is the most common type of breast cancer among older postmenopausal women, accounting for approximately 75 percent of all cases in this population.

ER+ breast cancer tumor cells contain a protein, or receptor, that responds to estrogen and stimulates tissue growth in a woman’s breasts, increasing her risk of breast cancer.

During the UCSF-led study, which took place at 180 clinical centers, 7,705 postmenopausal women (mean age 66.5 years) with osteoporosis who were at a low to average risk of developing breast cancer were randomized to receive either 60 milligrams (mg) or 120 mg of raloxifene per day, or a matching placebo. Of these women, 2,572 received 120 mg of raloxifene daily; 2,557 received 60 mg and one placebo tablet daily; and 2,576 received two placebo tablets daily. Women with a history of breast cancer or those who were taking estrogen were excluded from the study.

Among the 7,705 women enrolled in the study, Cummings reports that a total of 54 cases of breast cancer were confirmed, 40 of which were classified as invasive. Thirteen cases of invasive breast cancer developed among the 5129 women who received raloxifene versus 27 among the 2576 women who took a placebo.

“These results are dramatic because very few preventive treatments have reduced the risk of any disease this much,” Cummings says. “However, as with any postmenopausal hormonal therapy, there are both benefits and risks associated with the drug and therefore women should talk to their doctors about different treatment options.”

Raloxifene belongs to a class of drugs called selective estrogen receptor modulators (SERMS). SERMS work by mimicking the effects of estrogen in some parts of the body—for example SERMS mimic the positive effects of estrogen on a woman’s bones and cholesterol levels—while inhibiting estrogen’s “bad” effects on a woman’s risk of breast cancer.

One of the most significant benefits of raloxifene is that it reduces the risk of breast cancer among postmenopausal without causing an apparent increase in uterine cancer—a side effect associated with other drugs in its class such as tamoxifen. 

Some of the reported side effects of raloxifene include hot flashes, leg cramps, peripheral edema and flu-like symptoms.  There was also an increased incidence of blood clots among women who received raloxifene. After 40 months of follow-up, 38 cases of venous thrombosis (blood clot in a major vein) and 17 cases of pulmonary embolus (blood clot in a lung) developed among women in the study who were taking raloxifene. However, because these conditions are rare, Cummings says that the three-fold increase in risk among women receiving raloxifene translates to a 0.6 percent excess risk over a three-year period.

He adds that women with a history of venous thrombosis or pulmonary embolus should not take raloxifene, tamoxifen or estrogen.

Further, more women in the raloxifene group (1.2 percent) reported a new or worsening condition of diabetes compared to those in the placebo group. However, the diabetic women’s sugar levels did not increase nor did their need for treatment for the disease during the study.

The MORE trial was conducted at 180 clinical centers in 25 countries (mostly in the United States and Europe) and was designed primarily to determine the effect of raloxifene on women’s bone mineral density and vertebral fracture risk. The incidence of breast cancer among study participants was evaluated as a secondary endpoint of the MORE trial.

Cummings says that the study will continue for another four years to determine the long-term effects of raloxifene on the prevention of breast cancer among postmenopausal women. This clinical trial, called the Continuing Outcomes Relevant to Evista (CORE) study, will follow a sub-population of MORE participants.

Raloxifene was approved for the prevention of osteoporosis by the Food and Drug Administration (FDA) in December 1997. It is marketed as Evista by Eli Lilly and Co.

Other authors of the paper include Dennis Black, PhD; and Deborah Grady, MD, University of California, San Francisco; Steven Eckert, PhD; Kathryn A. Krueger, MD; Joan E. Glusman, MD; and Thomas Nickelsen, MD, PhD, Eli Lilly and Co.; Larry Norton, MD, Sloan Memmorial Cancer Center; Nina H. Bjarnason, MD, Center for Clinical and Basic Research, Ballerup, Denmark; Trevor J. Powles, PhD, Royal Marsden NHS Trust Hospital; Jane A. Cauley, DrPH, FRCP, University of Pittsburgh; Monica Morrow, MD, Northwestern University Medical School; Marc E. Lippman, MD, Georgetown University Medical Center; Alberto Costa, MD, European Institute of Oncology, Milano, Italy; V. Craig Jordan, PhD, DSc, Robert H. Lurie Cancer Center, Northwestern University.