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 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.
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 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
The double-blind, randomized study will enroll 22,000 postmeno-pausal
More than 300 institutions are expected to participate in the trial.
Dr. Jordan analyzed integrated data from multicenter, double-blind,
placebo-controlled, randomized trials of raloxifene in 10,553
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."