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
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
(Our Organization
is not responsible for the content of Internet sites.)
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 |
