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.
|
October 2002
(October is National Breast Cancer Awareness Month)
Risk-Benefit
Ratio in Preventive Setting Still Unclear
Some
American Physicians Disagree With Recent Findings
About
Tamoxifen
What
Does Previous Research Say?
Cracking
the Mystery of Breast Cancer
Online
Resources
In Other Breast Health
News:
Cracking
the Mystery of Breast Cancer
Researchers
map how changes to BRCA2 gene can lead to cancer
Mutations in a protein
called BRCA2 can lead to breast and ovarian cancers, says a study
in a recent issue of Science.
Memorial Sloan-Kettering
Cancer Center researchers have uncovered the function of BRCA2 and
the dangerous nature of mutations in the protein.
Previous research showed
BRCA2 is a protective protein that prevents cancer development,
but it was not clear this occurred. The researchers mapped out the
structure of the BRCA2 protein and showed that it interacts directly
with DNA to help repair genetic damage.
Left uncorrected, genetic
damage can result in unstable chromosomes that can lead to cancer.
"If BRCA2 is altered or
missing, it leads to a dangerous accumulation of genetic errors,"
says study senior author Nikola P. Pavletich, head of Sloan-Kettering's
laboratory of structural biology of oncogenes and tumor.
"By studying the normal
function of BRCA2, we can understand how changes in the protein
contribute to the development of cancer," Pavletich says.
Always consult your physician
for more information.
Online
Resources
American
Cancer Society
The
Lancet
National
Alliance of Breast Cancer Organizations
National
Breast Cancer Coalition
National
Cancer Institute
National
Surgical Adjuvant Breast and Bowel Project
Science
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