Tamoxifen
William M. Buchholz, MD.
Internal
Medicine, Hematology, Oncology
Tamoxifen
is a "selective estrogen receptor modulator" or SERM. In English,
this means that it acts like estrogen in some tissues (bone, liver,
uterus) and like an anti-estrogen in other tissues (notably, the
breasts). It is used to treat metastatic breast cancer, prevent
a known breast cancer from returning (adjuvant therapy), prevent
breast cancer from starting in the first place (primary prevention),
and sometimes used for its desirable side effects on preventing
osteoporosis and lowering cholesterol.
Like
all medicines, tamoxifen (trade name, Nolvadex) has side effects.
Some of these side effects are serious and must be carefully considered
before taking the drug. Other side effects are very rare, some are
inconvenient but not dangerous, and some are ascribed to tamoxifen
but may be due to something else.
The
value of tamoxifen depends on the balance of good and bad effects.
You should understand the benefits of any medicine before taking
it. You should also know what side effects can occur, how likely
they are, and whether you can (or need to) prevent these side effects.
Benefits
of Tamoxifen
In
tumors that have estrogen or progesterone receptors ("ER or PR positive"),
tamoxifen is used to treat metastatic disease. Sixty to 70% of women
with ER or PR positive tumors respond to treatment.
Tamoxifen is used as adjuvant therapy, particularly in post-menopausal
women with ER or PR positive tumors. Depending upon the receptors
and menopausal status of the patient, it can reduce the chances
of recurrence by up to 36%. (For ER positive premenopausal women
there is a 19% improvement.)
For women who are healthy but have a "high risk" of developing cancer,
tamoxifen can reduce the risk of breast cancer by 45%.
Tamoxifen can lower cholesterol and prevent heart disease. Various
studies have shown:
1)
33-63% decrease in heart attacks
2) 8-15% decrease in total cholesterol
3) 16-26% decrease in LDL (bad guy) cholesterol
Tamoxifen helps osteoporosis:
1) Spine bone density increases from.4 to 2.4%
2) Hip bone density increases about.6%
3) Over all fractures are reduced by 35%
Side
effects of Tamoxifen
The
following list of side effects is taken from various controlled
studies.
The risk of uterine cancer is doubled from approximately 1 in 1000
to 2 in 1000 women. This affects only postmenopausal women, is almost
always Stage 1 when discovered, and is completely cured with hysterectomy.
The best test is a pelvic exam by a gynecologist. Sometimes an ultrasound
is used to measure the size of the uterine lining. If you have postmenopausal
bleeding while on tamoxifen you should be checked by your doctor.
The risk of blood clots in veins increases with age. The rate for
women not taking any hormones varies from 1/1000 women age 50-60
to 3-6/1000 ages 70-80. Tamoxifen doubles the risk of blood clots
to 1/100 women ages 70-80. For the most part, these clots in the
leg veins are uncomfortable but not dangerous. They can be fatal
if they travel to the lungs (pulmonary embolus). Women with a prior
history of deep vein thrombosis or pulmonary emboli should be cautious
and speak to their doctor before taking tamoxifen.
Hot
flashes while on tamoxifen are more common than without the drug.
In one study 56% of women on tamoxifen reported hot flashes while
43% of women taking placebo also experienced them. This suggests
that there are several different causes for hot flashes in the group:
stopping hormones that had prevented hot flashes, chemotherapy causing
menopause, age-related menopause, etc.
In one study a vaginal discharge occurred in 22% of women on tamoxifen
as opposed to 11% of women taking placebo. This discharge was generally
clear and could be distinguished from an infection such as yeast.
A bloody discharge should be evaluated by a physician.
In studies comparing overall quality of life, tamoxifen is not different
from placebo. In fact, in one study, the control group reported
feeling less feminine and having less sexual desire than the tamoxifen
group. There is an average weight gain of 1.3 kg with tamoxifen
compared to 1.1 kg on placebo (net 7 oz gain).
There
is no increase in liver tumors with tamoxifen in humans. Studies
in rats which showed such tumors do not apply to humans because
rodents metabolize tamoxifen differently than people.
In
the following study by Love (Love, et al. Arch Int Med 1991; 151:1842-47)
140 post menopausal women were studied. Half received placebo and
the other half received Tamoxifen for 2 years. The following table
shows the frequency of side effects in women taking placebo (i.e.,
no direct effect from drug), taking Tamoxifen, and whether the difference
is significant (NS = not significant). What is most striking is
the prevalence of significant symptoms in the group taking an inactive
substance.
Placebo Tamoxifen Significance
Hot Flashes
45% 67%
p<.01
Severe Hot Flashes 8%
20% p<.04
Flushed face
33% 47%
NS
Gynecologic Symptoms* 15%
30% p<.05 *discharge, dryness,
discomfort
Racing heart
15% 25%
NS
Bone pain
23% 31%
NS
Joint pain
49% 52%
NS
Nausea
20% 20%
NS
Sweaty hands
21% 23%
NS
Vomiting
0% 0%
NS
Headache
50% 32%
p<.04
Insomnia
49% 55%
NS
Irritability
56% 49%
NS
Depression
36% 32%
NS
Fatigue
67% 72%
NS
Heartburn
23% 17%
NS
There
are anecdotal reports of other side effects including memory loss,
cataracts and other visual problems. I have not been able to find
controlled studies confirming or refuting these.
CONCLUSIONS
As
with any medicine there are advantages and disadvantages. The decision
to take or not take Tamoxifen should not be based upon fear, either
of the side effects or of the possibility of cancer. Many the side
effects ascribed to Tamoxifen occur frequently in a comparable group
of women who are not taking the drug. This has caused undue fear
of the medicine. Conversely, much of the hype in the media about
breast cancer has caused unwarranted expectations that Tamoxifen
is a miracle drug. The decision to take this medicine should be
based upon a balance of the factual data about the drug and your
clinical condition, the level of risk you are willing to take, and
your ability to cope with any side effects of treatment.
The
women for whom there are the largest advantages are:
1) those who are at risk (more than 10 %) for the return of a diagnosed
cancer;
2) those who should not take estrogen because of prior cancer and
are at risk of osteoporosis or have an elevated cholesterol;
3) those who have a high(er) risk of developing a new breast cancer
in the future because of age, a family history of breast cancer,
or a personal history of a high risk lesion.
After reading this if you have any questions please write them down
and arrange a time to meet with me so that I can answer them.
William
M. Buchholz, M.D. rev 2.27.99
©Buchholz
1999 All rights Reserved
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