Gene
Finding Provides Clues To Tamoxifen Success
Scientists
Enhance Understanding Of What Treatments Work Best
The activity
of two genes may tell physicians who will succeed on tamoxifen therapy
for breast cancer and, more importantly, who will fail, according
to a new report in the medical journal Cancer Cell.
A new study that found
if high levels of a gene called HOXB13 or low levels of a gene known
as IL17BR were expressed, tamoxifen therapy was not successful.
The simple gene test was
more than 80 percent accurate in predicting a recurrence of the cancer.
Tamoxifen is a breast cancer
medication that blocks the effects of estrogen. This is important
because, in many cases, breast cancer cells are fueled by estrogen.
Estrogen-blocking drugs
such as tamoxifen are often prescribed after a woman has surgery for
breast cancer that is hormone-sensitive to try to keep the cancer
from returning.
Hormone-sensitive breast
cancers are also known as hormone receptor positive.
"Thirty to 40 percent of
women who are hormone receptor positive will recur even if taking
tamoxifen," explains study co-author Dr. Dennis Sgroi, director of
breast pathology at Massachusetts General Hospital in Boston.
"Right now, we have no
way of knowing who will do well," he says. "What we wanted to do was
to find something that could identify the population that won't do
well."
Gene
"Profiling" Aids Researchers
Dr. Sgroi and his colleagues
examined frozen tumor samples from the initial biopsies of 60 women
who had hormone receptor positive breast cancer. All of the women
had been treated with tamoxifen.
Thirty-two women from this
sample remained disease-free up to 10 years later, while 28 women
had a recurrence of cancer or their cancer spread to other areas of
the body.
Dr. Sgroi says the researchers conducted
detailed gene expression profiling and found two genes that were strongly
associated with a recurrence of cancer - HOXB13 and IL17BR.
Dr. Sgroi said the researchers
do not know for sure what role these genes play in the development
and spread of breast cancer. They suspect that HOXB13 may help cancer
cells migrate and invade other cells. The role of IL17BR is less clear.
Dr. Sgroi says other research has suggested this gene may play a role
in inflammation and the immune system.
"Independently, each gene
predicted recurrence, but when we looked at them together, we did
even better," he says. "We were able to predict with 81 percent accuracy
[by looking at the ratio of expression between the two genes]."
To confirm these findings,
the researchers validated the initial results with a smaller group
of women who also had hormone receptor positive cancer and received
tamoxifen therapy. The findings were similar.
"We are cautiously optimistic,"
Dr. Sgori reports. "These findings need to be validated in a population-based
study, which we're in the process of doing."
Tailoring
Treatment Looks Promising
But, he adds, it appears
that "we've come up with a simple test that may assist an oncologist
in deciding whether tamoxifen therapy alone is adequate."
"Not all breast cancers
are alike," says Dr. Duane Superneau, chief of the section of medical
genetics at Ochsner Clinic Foundation Hospital in New Orleans.
"This could give clinicians
a means to see what therapy would be most individually suited," Dr.
Superneau says. "Our strategies for treatment could be more directly
applied for the individual and their individual disease."
Dr. Superneau says that
any lab that currently does gene testing should be able to conduct
these tests.
Both Drs. Sgroi and Superneau
say that in addition to learning who will respond well to tamoxifen,
the knowledge that a higher expression of HOXB13 and a lower expression
of IL17BR occur in tamoxifen-resistant cancers could also help direct
future research into treating those cancers.
Always consult your physician
for more information.
|
July 2004
Gene
Finding Provides Clues To Tamoxifen Success
Gene
"Profiling" Aids Researchers
Tailoring
Treatment Looks Promising
Hormone
Therapy Defined
Online
Resources
Other
Resources:
St.
John's Mercy Cancer Services
Find
a St. John's Mercy Physician
Breast
Health Information
Women's
Health Information
St.
John's Mercy Classes and Programs
Hormone
Therapy Defined
Hormone therapy is used
to prevent the growth, spread, and recurrence of breast cancer.
Hormones are chemicals
produced by glands, such as the ovaries and testicles. Hormones help
some types of cancer cells to grow, such as breast cancer and prostate
cancer.
The female hormone estrogen
can increase the growth of breast cancer cells in some women.
Hormone therapy may be
considered for women whose breast cancers test positive for estrogen
or progesterone receptors.
A hormone receptor test
measures the amount of certain proteins (called hormone receptors)
in cancer tissue.
Hormones (such as estrogen
and progesterone that naturally occur in the body) can attach to these
proteins.
If the test is positive,
it indicates that the hormone is probably helping the cancer cells
to grow. In this case, hormone therapy may be given to block the way
the hormone works and help keep the hormone away from the cancer cells
(hormone receptors).
If the test is negative,
the hormone does not affect the growth of the cancer cells, and other
effective cancer treatments may be given.
Always discuss the results
of the hormone receptor test with your physician.
An antiestrogen drug frequently
used, called tamoxifen (Nolvadex®), blocks the effects of estrogen
on the growth of malignant cells in breast tissue.
However, tamoxifen does
not stop the production of estrogen. Side effects that may occur when
taking tamoxifen include hot flashes, nausea or vomiting, vaginal
spotting, fatigue, headaches, and skin rash.
Taking tamoxifen also increases
the risk of endometrial cancer (involves the lining of the uterus)
and uterine sarcoma (involves the muscle tissue of the uterus), both
cancers of the uterus. There is also a small risk of blood clots and
stroke.
Always consult your physician
for more information.
Online
Resources
American
Cancer Society
American
Society for Clinical Oncology
Centers
for Disease Control and Prevention (CDC)
National
Cancer Institute
National
Institutes of Health (NIH)
National
Women's Health Information Center
Susan
G. Komen Breast Cancer Foundation
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