[MOL] NY Times re: Tamoxifen/Evista [01032] Medicine On Line


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[MOL] NY Times re: Tamoxifen/Evista



Round 3 in Cancer Battle: A 5-Year Drug Regimen
    [05/11/99; New York Times (Free Registration Required)]



                    Having completed the first two phases of treatment for an
early breast cancer -- a
                    lumpectomy and six weeks of radiation therapy -- I have
now begun the third and, in
                    a way, the most exciting phase: five years of daily
treatment with the drug
              tamoxifen. 


              Unlike traditional cancer chemotherapy, tamoxifen does not kill
cells and does not cause
              nausea and hair loss. Tamoxifen is more like a growth
regulator. It is an estrogen-like
              compound that acts in the breast as an antiestrogen, preventing
the natural hormone from
              stimulating the growth of breast cancer cells. 


              Tamoxifen has been around for about 20 years. It was first used
to treat advanced breast
              cancer, then to prevent recurrence of less advanced disease.
Now it is being used to prevent
              breast cancer from occurring in the first place in women at
high risk of developing the
              disease. 


              Factors that contribute to a woman's risk of developing breast
cancer include being over 60,
              having a family history of breast cancer, having had a
noninvasive breast cancer or
              precancerous breast abnormalities, having begun to menstruate
before the age of 12 and
              having had no children or a first child after age 30. 


              The First Cancer Preventive 


              I admit to being confused and disappointed when my surgeon
announced gleefully that my
              cancer was highly sensitive to hormone stimulation, as
indicated by a test for estrogen and
              progesterone receptors on the cancer cells. To me that meant I
would probably never again be
              able to take postmenopausal hormones, which could protect my
heart, bones and brain from
              premature deterioration and which prevented hot flashes and
vaginal dryness. 


              The surgeon was pleased because being
estrogen-receptor-positive meant that my tumor was
              slower growing, and that I could reap the maximum protection
from tamoxifen, which has
              been shown to cut in half the risk of recurrence of the
original breast cancer as well as the
              development of a second cancer in the opposite breast. 


              Estrogen receptors are found in about 65 percent to 80 percent
of breast cancers in
              postmenopausal women and 45 percent to 60 percent of cancers in
premenopausal women. 


              The higher the level of estrogen receptors in a woman's tumor,
the greater the survival
              benefit associated with taking the drug. Women whose cancers
are
              estrogen-receptor-negative reap some benefit from tamoxifen as
well, suggesting that the
              drug has other as-yet undiscovered actions. 


              Studies have indicated that five years of daily tamoxifen is
more protective than one or two
              years and as good or better than taking the drug for 10 years.
Its protective effects have been
              shown to persist for at least five years after the drug is
stopped. 


              Most exciting, last year tamoxifen was shown in a study of more
than 13,000 women to
              reduce by 50 percent the development of a first cancer in women
considered at high risk for
              the disease. This made tamoxifen the first drug found to
prevent cancer, although it is still
              not known for sure whether the protection is permanent. But
tamoxifen may not be helpful in
              women who carry cancer-promoting mutations of the genes BrCa1
and BrCa2. 


              Dr. D. Lawrence Wickerham, an oncologist at Allegheny
University in Pittsburgh and a
              co-leader of national tamoxifen studies, said, "The cancers
that developed in
              tamoxifen-treated women tended to be smaller and were found at
an earlier stage," meaning
              they were more readily cured. Describing other benefits found
in the studies, Dr. Wickerham
              said: "Women taking tamoxifen suffered fewer bone fractures of
the wrist, hip and spine and
              their cholesterol level dropped by 12 to 20 percent.
Furthermore, there is no evidence that
              tamoxifen is associated with weight gain, depression, nausea or
cancers of the ovary, liver
              and gastrointestinal tract." 


              The effects of tamoxifen on the brain are unknown, though there
is no evidence of any ill
              effect, like memory impairment. 


              Unwanted Effects, Too 


              But for all the good tamoxifen does, it has certain major and
minor disadvantages. Like
              estrogen, it raises the risk of developing a relatively
uncommon cancer of the uterus,
              endometrial cancer, a disease that can be detected early
through routine monitoring and cured
              by surgery and, if needed, radiation therapy. Its other serious
side effect -- one that is shared
              by estrogen as well -- is an increased risk of blood clots,
which are occasionally fatal.
              Nonetheless, Dr. V. Craig Jordan of Northwestern University's
cancer center, who did
              pioneering research on tamoxifen, said the survival benefit
from the drug for a woman like
              me who has had breast cancer outweighs the risk of death from
its effects on the uterus and
              blood by about 30 times. 


              Stimulation of the growth of the endometrium, or uterine
lining, which could increase the
              risk of cancer, occurs in a small percentage of women who take
tamoxifen. Nonetheless,
              women may be advised to have a baseline uterine examination
before starting tamoxifen,
              followed by annual checkups to see if the drug is stimulating
growth of the endometrium.
              This examination can be done in a doctor's office as an
endometrial biopsy or painlessly by
              transvaginal ultrasound. A woman who experiences an unusual
vaginal discharge or bleeding
              while on tamoxifen should report that to her gynecologist
without delay. 


              On a less serious note, tamoxifen also causes hot flashes in a
quarter to a third of users and
              an annoying vaginal discharge in about 5 percent to 10 percent
of women. The hot flashes
              may seriously disrupt a woman's life. But they usually diminish
with time, and their
              intensity may be diminished by daily consumption of soy
products like tofu and ground
              flaxseed. 


              A New Class of Drugs 


              Tamoxifen, sold as Nolvadex, is the first of a new class of
drugs called SERM's, for
              selective estrogen receptor modulators. These compounds compete
with natural estrogen for
              a docking site on cells throughout the body. When these sites,
called receptors, are occupied
              by tamoxifen, estrogen cannot hook on properly and exert its
usual effects. 


              A more recent addition to this class is raloxifene, sold as
Evista, which seems to share most
              of the characteristics, good and bad, of tamoxifen, and several
other such drugs are in
              various stages of development. The ultimate goal is to find a
compound that does all the good
              that estrogen does, including reducing the risk of heart
disease and osteoporosis, stimulating
              brain cells and preventing menopausal symptoms, but that has
none of estrogen's bad
              effects, especially raising the risk of cancers of the breast
and uterus and causing blood clots.

              Raloxifene, which is approved for the prevention of bone loss,
also appears to protect the
              breast and heart but without stimulating cell growth and cancer
in the uterus. But like
              tamoxifen, it can increase clotting and induce hot flashes, and
it is not yet known whether it
              is as good as or better than tamoxifen in preventing breast
cancer. 


              A study to determine this, called STAR (for Study of Tamoxifen
and Raloxifene), is just
              getting under way. The study, sponsored by the National Cancer
Institute, will involve
              22,000 women and is expected to last 5 to 10 years. 


              "At the moment, it's too early to use raloxifene to prevent
breast cancer outside of a clinical
              trial," Dr. Wickerham said during a teleconference sponsored by
Cancer Care Inc. 


              "We don't yet know raloxifene's long-term benefits or risks." 


              He suggested that women interested in possibly participating in
the STAR trial call the
              National Cancer Institute's hot line, (800) 4-CANCER, or sign
on to the Web site of the
              National Surgical Adjuvant Breast and Bowel Project. 


              More information on tamoxifen can be found in a new paperback
book, "Tamoxifen," by Dr.
              John F. Kessler and Greg A. Annussek (Avon, $5.99).
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