Raloxifene imparts
anticancer benefit
By N. Seppa
When the osteoporosis drug raloxifene came on the market last year,
it offered women a way to strengthen their bones yet avoid the breast-cancer
risk associated with estrogen-replacement therapy. Now, researchers
report that raloxifene may actually prevent breast cancer in many women.
As part of a worldwide study to gauge raloxifene's effects on osteoporosis,
scientists gave the drug to two-thirds of a group of 7,705 postmenopausal
women with the brittle-bone disease. The other participants received
an inert substance. Neither the scientists nor the study participants
knew which pills contained the medication.
All participants also took calcium and vitamin D supplements daily
and received regular mammograms or breast ultrasound examinations in
addition to bone measurements.
During the 40-month study, 27 of the 2,576 women receiving the inert
pills developed breast cancer, while only 13 of the 5,129 women taking
raloxifene were diagnosed with the malignancy. In other words, breast-cancer
incidence with the drug was only one-fourth as great as without it,
the researchers report in the June 16 Journal of the American Medical
Association.
"It's a landmark study," says Michael B. Sporn, a pharmacologist at
Dartmouth Medical School in Hanover, N.H.
The drug seems to stifle invasive breast cancer, in which estrogen
induces uncontrolled cell growth, says study coauthor Steven R. Cummings,
an internist and epidemiologist at the University of California, San
Francisco. In about two-thirds of breast cancers in postmenopausal women,
the hormone fuels a tumor's growth, he says.
Estrogen circulating in the blood attaches to one of two estrogen-receptor
molecules in cells. The receptors then activate specific genes, inducing
a chain reaction of protein production that can lead to cell growth.
Such a flurry of activity initially poses little risk, but repeated
exposure to estrogen over a long period of time "is too much of a good
thing," says Leo Plouffe, a research physician at Eli Lilly and Co.
in Indianapolis, which makes raloxifene.
"If you consistently promote the growth of certain cells [with estrogen],
the cells might transform themselves into cancer cells," he says. Or,
if cancer is already present, the estrogen stimulus might abet the disease.
Raloxifene works by occupying the estrogen receptors, Cummings says.
When the drug thus blocks the receptor on a cancerous cell, estrogen
cannot bind and apparently the cell dies off, he says.
In its role as a bone-growth promoter, however, raloxifene mimics rather
than blocks estrogen's effects. Precisely how raloxifene can play one
role in one cell and another elsewhere remains unclear, Cummings says.
Raloxifene may provide yet another benefit: Women receiving the drug
in this study didn't show the increased incidence of uterine cancer
that previous research has associated with both estrogen and the anti-breast-cancer
drug tamoxifen.