| Release
Date: Nov. 6, 2002
Researchers at the University of
Arkansas for Medical Sciences (UAMS) have reported a possible
genetic explanation for why some women with breast cancer respond
better to conventional doses of the widely-used drug tamoxifen
than do others.
The scientists, affiliated with the Arkansas Cancer Research
Center at UAMS, Central Arkansas Veterans Healthcare System, and
the National Center for Toxicological Research at Jefferson, Ark.,
report in the Journal of the National Cancer Institute that
women with a "slow version" of the gene SULT1A1 have
lower survival rates on a typical post-surgery regimen of
tamoxifen.
"If other scientists are able to confirm these findings,
doctors will be able to adjust doses of tamoxifen for individuals
according to whether they have the low-activity gene," said
Susan Nowell, the research team leader and a doctoral student in
interdisciplinary toxicology at UAMS. The scientists estimate that
about 13 percent of women have the "slow" gene and may
need different doses of tamoxifen.
The researchers are studying
genetic factors in women's responses to tamoxifen in hopes that
physicians one day will be able to design custom prescriptions
based on individual patients' genetic make-up. This research has
the potential to provide physicians with the information to
determine how much of a drug will be effective as well as which
particular drug will work best for the individual patient.
"This is the goal of
pharmacogenetics - to be able to define the genetic basis of
individual response. We want our research to lead to the goal of
individualized pharmacology to make treatment for disease more
effective in the individual," Nowell said.
In some women, tamoxifen acts as an "anti-estrogen"
agent to prolong survival and combat recurrence of types of breast
cancer that are related to estrogen. However, the drug's
effectiveness has not been universal, prompting the scientists to
look for a genetic difference in women who show less improvement
in survival on tamoxifen therapy.
Their study involved 160 women who
had received tamoxifen and another 177 women with breast cancer
who had not. The women who did not receive the drug had similar
survival rates regardless of whether they possessed the "slow
version" of the gene, but the difference in responses was
evident in women who received tamoxifen. Women who had inherited
the "slow" gene from both parents were three times less
likely to survive as women who had two normal SULT1A1 genes, or
one "slow" and one normal gene. The scientists took into
account age, ethnicity, and stage of tumor at diagnosis, finding
that the genetic effect persisted even when those factors were
considered.
Nowell and other scientists and
physicians at the Arkansas Cancer Research Center next will
recruit patients with new diagnoses of breast cancer, who are to
receive tamoxifen therapy, for a long-term study of the effects of
tamoxifen in women with and without the "slow" gene.
Laura Hutchins, M.D., at the cancer center will recruit the
patients for that study, which the U.S. Department of Defense will
fund. Nowell holds a predoctoral fellowship with the U.S.
Department of Defense Breast Cancer Research Program.
# # #
Contact:
Leslie W. Taylor
501-686-8998
Wireless phone: 501-951-7260
leslie@uams.edu
Elizabeth F. Shores
501-686-8394
ShoresElizabethF@uams.edu
UAMS
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