SAN FRANCISCO--Raloxifene (Evista), an estrogen-receptor modulator used to treat osteoporosis, also has a protective effect against breast cancer, according to a 2-year randomized study and an overview analysis reported at ASCO. These findings require some caution in interpretation, since they were mainly observed in women with osteoporosis, a population that has a lower breast cancer risk than the general population.
Steven R. Cummings, MD, reported findings from the Multiple Outcomes of Raloxifene(Drug information on raloxifene) Evaluation (MORE) trial. Dr. Cummings is professor of medicine and epidemiology, University of California, San Francisco.
V. Craig Jordan, PhD, DSc, of the Lurie Cancer Center, Northwestern University, reported results of a second analysis of the same study that also included data from other placebo-controlled studies of raloxifene.
The MORE study is a randomized, double-blind trial designed to test the hypothesis that women assigned to raloxifene will have a lower risk of fractures than women assigned to placebo. It was not primarily designed to look at breast cancer risk.
The study enrolled 7,705 postmenopausal women up to age 80 (mean, 66.5 years). All had osteoporosis (hip or spine bone density below normal or vertebral fractures) and no history of breast or endometrial cancer. Patients were randomly assigned to receive raloxifene (60 or 120 mg/day) or a matching placebo, in a ratio of two active to one placebo. Results with the two doses were pooled because of their similarity.
Breast and endometrial cancer cases were assessed retrospectively from the safety database. Breast cancer was confirmed by pathology reports and/or original slides reviewed blindly as to treatment assignment.
Results at 33 Months
Dr. Cummings reported that after a median of 33 months of follow-up, raloxifene had reduced the risk of all breast cancers to about one-quarter to one-third the rates in the placebo group (see Figure).
The rate of invasive breast cancer decreased by 70% in the raloxifene group (P < .001). At the time of this report, 35 cases of breast cancer had been confirmed: 13 in the women assigned to raloxifene and 22 in the women assigned to placebo, for a relative risk of 0.3.
There were no excess cases of endometrial cancer among women treated with raloxifene, with four cases in the raloxifene group and four in the placebo group. However, two of the endometrial cancers in the raloxifene group were diagnosed during the first month after randomization and were likely preexisting. "If these two cases are excluded, the estimate of relative risk is 0.25," Dr. Cummings said.
With regard to adverse events, Dr. Cummings said, "We are seeing the same increase in the risk of blood clots forming in major veins with raloxifene as is seen with tamoxifen(Drug information on tamoxifen) or estrogen."
Dr. Cummings concluded that, "in older women with osteoporosis, approximately 2.5 years of raloxifene substantially reduces the risk of developing breast cancer" but that long-term effectiveness is unknown. This trial is expected to continue for another 5 years.
NSABP Plans Trial of Tamoxifen vs Raloxifene for Breast Cancer Prevention
The NCI has approved the NSABPs plan for a clinical trial that will compare tamoxifen and raloxifene in postmenopausal women at high risk for developing breast cancer. Recruitment for the trial, known as STAR (Study of Tamoxifen and Raloxifene), is scheduled to begin in the fall of 1998.
The double-blind, randomized study will enroll 22,000 postmeno-pausal women age 35 or older who are at increased risk of breast cancer using assessment criteria similar to those in the BCPT. The women will receive either tamoxifen (20 mg orally) or raloxifene (60 mg orally) for 5 years. Participants will be monitored annually via blood tests, mammography, physical exam, and gynecologic exam.
More than 300 institutions are expected to participate in the trial. For more information about the study, contact the NSABP at its website (www.nsabp.pitt.edu), by fax (412-330-4660), or by mail (NSABP, East Commons Professional Building, Four Allegheny Center-5th Floor, Pittsburgh, PA 15212-5234).
Dr. Jordan analyzed integrated data from multicenter, double-blind, placebo-controlled, randomized trials of raloxifene in 10,553 postmenopausal women.
For all studies combined, including the MORE trial, 58 cases of newly diagnosed breast cancer were reported and used to compare incidence rates between raloxifene and placebo.
At 33 months follow-up, ralox-ifene had reduced the incidence of breast cancer by 54% overall, 55% for invasive cancers, and 70% for ER+ cancers. "This is consistent with selective prevention of breast cancer by an ER-mediated mechanism," he said. "These are strong preliminary data to go forward with the study comparing tamoxifen and raloxifene."