Tamoxifen
Study Raises Risk-Benefit Questions
But
American physicians defend breast-cancer therapy
The
drug tamoxifen, NOLVADEX® (tamoxifen citrate), can reduce the risk
of breast cancer in women with higher odds of developing the disease,
but a new study says it is not clear if the benefits of the drug outweigh
its side effects. 
Researchers
in Britain, Australia, and New Zealand found a 32 percent reduction
in the risk of breast cancer in 3,578 women taking the hormone therapy.
However, it turned up a doubling in potentially life-threatening blood
clots, especially in women undergoing surgery or prolonged immobilization.
And it found more than a doubling in the risk of death—related
to clots after surgery—compared with 3,566 women receiving a placebo
treatment.
Risk-Benefit
Ratio in Preventive Setting Still Unclear
Dr.
Jack Cuzick, the leader of the IBIS-I (International Breast Cancer Intervention)
study, said in a statement: "Although when used as adjuvant therapy
for breast cancer, tamoxifen can clearly reduce the risk of recurrence
and death, at present the overall risk-to-benefit ratio in the preventive
setting is still unclear. Further long-term follow-up to study breast-cancer
incidence and mortality, other causes of death, and side effects in
the current trials remains essential."
Some
American Physicians Disagree With Recent Findings
However,
some American physicians disagree that tamoxifen was on a bubble. Dr.
D. L. Wickerham, associate chairman of the National Surgical Adjuvant
Breast and Bowel Project (NSABP), a major cancer research effort in
the United States, says the results "confirm that tamoxifen is an effective
drug." As for the clotting risk, Wickerham says that is "not news. Tamoxifen
has been around since the 1960s," and physicians have long known about
the elevated incidence of blood cots.
Wickerham,
a breast cancer expert at Allegheny General Hospital in Pittsburgh,
adds the risk is the same as that of estrogen in hormone replacement
therapy for postmenopausal women: not negligible, but not so great to
prevent them from taking it.
The
researchers report their findings in a recent issue of The Lancet.
About
Tamoxifen
Tamoxifen
is sold as Nolvadex by AstraZeneca. Many take it for the treatment of
existing breast tumors, and a smaller fraction use it to prevent cancer
from occurring.
The
drug is a selective estrogen receptor modulator, or SERM. It binds to
estrogen receptors and alters how cells react to the hormone. In the
breast, it restrains estrogen activity, reducing the growth of cells.
In the endometrium, it increases estrogen activity, pushing cell growth.
What
Does Previous Research Say?
Three
previous clinical trials of tamoxifen have shown it can cut the risk
of breast cancer in high-risk women, such as those with a close relative
with the disease, by about 50 percent over five years. That is in the
ballpark of the latest study, which included more than 7,100 women between
the ages of 35 and 70.
The
researchers did see more uterine cancers in the women taking tamoxifen,
11 versus five, but the difference was not statistically significant
and the tumors were easily removed by hysterectomy.
However,
the clotting risk may be more troublesome, the scientists say. While
some of the clots—roughly half of which were in the leg veins—occurred
after leg surgery or a fracture, many others were spontaneous.
All
of the excess deaths in the tamoxifen group occurred after surgery,
the researchers say. As a result, "a wise precaution would be to discontinue"
the drug before any operation and use anti-clotting therapy during the
procedure. Tamoxifen should be resumed only when the woman is able to
move around well.
Dr.
Clifford Hudis, chief of the breast cancer medicine service at Memorial
Sloan-Kettering Cancer Center in New York City, says the latest research
would be concerning had other studies not found no increased risk of
death from tamoxifen. But "all the other studies show that you lower
your breast cancer risk and the risk of death is neutral or better."
Still,
Hudis says it is true that physicians need to refine their risk-benefit
profile for the drug, especially in determining which women are the
best candidates for therapy. Hudis considers tamoxifen most appropriate
as a preventive in women at high risk of breast cancer. The IBIS study,
he notes, included many women at moderately elevated risk of the disease.
Always
consult your physician for more information.
|
