What is tamoxifen?
Tamoxifen (Nolvadex®) is a medication in pill form
that interferes with the activity of estrogen (a hormone). Tamoxifen has
been used for more than 20 years to treat patients with advanced breast
cancer. It is used as adjuvant, or additional, therapy following primary treatment for early stage breast cancer. In women at high risk of
developing breast cancer, tamoxifen reduces the chance of developing the
disease. Tamoxifen continues to be studied for the prevention of breast
cancer. It is also being studied in the treatment of several other types
of cancer. It is important to note that tamoxifen is also used to treat
men with breast cancer.
How does tamoxifen work on breast cancer?
Estrogen promotes the growth of breast cancer cells. Tamoxifen works against the effects of estrogen
on these cells. It is often called an "anti-estrogen." As a treatment
for breast cancer, the drug slows or stops the growth of cancer cells
that are present in the body. As adjuvant therapy, tamoxifen helps prevent the original
breast cancer from returning and also helps prevent the development of
new cancers in the other breast.
Are there other beneficial effects of tamoxifen?
While tamoxifen acts against the effects of estrogen in breast
tissue, it acts like estrogen in other tissue.
This means that women who take tamoxifen may derive many of the
beneficial effects of menopausal estrogen replacement therapy, such as lower blood cholesterol and slower bone loss (osteoporosis).
Can tamoxifen prevent breast cancer?
Research has shown that when tamoxifen is used as adjuvant therapy
for early stage breast cancer, it reduces the risk of recurrence of the original cancer and also reduces the
risk of developing new cancers in the other breast. Based on these
findings, the National Cancer Institute (NCI) funded a large research study to determine the
usefulness of tamoxifen in preventing breast cancer in women who have an
increased risk of developing the disease. This study, known as the
Breast Cancer Prevention Trial (BCPT), was conducted by the National
Surgical Adjuvant Breast and Bowel Project (NSABP), a component of the NCI's Clinical Trials Cooperative Group Program. This study found a 49
percent reduction in diagnoses of invasive breast cancer among women who
took tamoxifen. Women who took tamoxifen also had 50 percent fewer
diagnoses of noninvasive breast tumors, such as ductal or lobular carcinoma in situ. However, there are risks
associated with tamoxifen. Some are even life threatening. The decision
to take tamoxifen is an individual one: The woman and her doctor must
carefully consider the benefits and risks of therapy.
Women with an increased risk of developing breast cancer have the
option to consider taking tamoxifen to reduce their chance of developing
this disease. They may also consider participating in the Study of
Tamoxifen and Raloxifene (see question 5).
At this time, there is no evidence that tamoxifen is beneficial for
women who do not have an increased risk of developing breast cancer.
What is the Study of Tamoxifen and Raloxifene (STAR), and how can a
woman learn more about it?
The Study of Tamoxifen and Raloxifene (STAR) is a clinical trial (a research study conducted with
people) designed to see whether the osteoporosis drug raloxifene
(Evista®) is more or less effective than tamoxifen in reducing the
chance of developing breast cancer in women who are at an increased risk
of developing the disease. Raloxifene may have breast cancer risk
reduction properties similar to those found in tamoxifen. This study
will also examine whether raloxifene has benefits over tamoxifen, such
as fewer side effects.
The STAR trial, which began in June 1999, is being conducted by the
NSABP. It will involve about 22,000 postmenopausal women who are at
least 35 years old and are at increased risk for developing breast
Women can learn more about the STAR trial in several ways. They can
call NCI's Cancer Information Service at 1–800–4–CANCER
(1–800–422–6237). The number for deaf and hard of hearing callers with
TTY equipment is 1–800–332–8615. Information is also available on
NSABP's Web site at http://www.nsabp.pitt.edu/ or on the Study of Tamoxifen
and Raloxifene (STAR) Trial Digest Page on the NCI's Web site at http://www.cancer.gov/star on the Internet.
What are some of the more common side effects of taking
In general, the side effects of tamoxifen are similar to some of the
symptoms of menopause. The most common side
effects are hot flashes and vaginal discharge. Some women experience irregular
menstrual periods, headaches, fatigue, nausea and/or vomiting, vaginal
dryness or itching, irritation of the skin around the vagina, and skin rash. As is the case with menopause,
not all women who take tamoxifen have these symptoms. Men who take
tamoxifen may experience headaches, nausea and/or vomiting, skin rash,
impotence, or a decrease in sexual interest.
Does tamoxifen cause cancers of the uterus?
Tamoxifen increases the risk of two types of cancer that can develop
in the uterus: endometrial cancer, which arises in the lining of the
uterus, and uterine sarcoma, which arises in the muscular wall of the
uterus. Like all cancers, endometrial cancer and uterine sarcoma are
potentially life-threatening. Women who have had a hysterectomy (surgery to remove the uterus) and are taking tamoxifen
are not at increased risk for these cancers.
In the BCPT, women who took
tamoxifen had more than twice the chance of developing endometrial
cancer compared with women who took a placebo (an inactive substance
that looks the same as, and is administered in the same way as,
tamoxifen). The risk of endometrial cancer in women taking tamoxifen
was in the same range as (or less than) the risk in postmenopausal
women taking single-agent estrogen replacement therapy. This risk is
about 2 cases of endometrial cancer per 1000 women taking tamoxifen
Most of the endometrial cancers that have occurred in women taking
tamoxifen have been found in the early stages, and treatment has
usually been effective. However, for some breast cancer patients who
developed endometrial cancer while taking tamoxifen, the disease was
Information collected by the U.S. Food
and Drug Administration indicates that women who have used tamoxifen
for breast cancer treatment or prevention have an increased risk of
developing uterine sarcoma. Review of all the NSABP clinical trials
using tamoxifen confirmed an increased risk of this rare cancer. In
the BCPT, there are about 2 cases per 10,000 women taking tamoxifen
each year. Research to date indicates that uterine sarcomas are more
likely to be diagnosed at later stages than endometrial cancers, and
may therefore be harder to control and more life-threatening than
Abnormal vaginal bleeding and lower abdominal (pelvic) pain are symptoms of cancers of the uterus.
Women who are taking tamoxifen should talk with their doctor about
having regular pelvic examinations, and should be checked promptly if
they have any abnormal vaginal bleeding or pelvic pain between scheduled
Does tamoxifen cause blood clots or stroke?
Data from large treatment studies suggest that there is a small
increase in the number of blood clots in women taking tamoxifen,
particularly in women who are receiving anticancer drugs (chemotherapy)
along with tamoxifen. The total number of women who have experienced
this side effect is small. The risk of having a blood clot due to
tamoxifen is similar to the risk of a blood clot when taking estrogen
Women in the BCPT who took tamoxifen also had an increased chance of
developing blood clots and an increased chance of stroke.
Does tamoxifen cause eye problems?
As women age, they are more likely to develop cataracts (a clouding
of the lens inside the eye). Women taking tamoxifen appear to be at
increased risk for developing cataracts. Other eye problems, such as
corneal scarring or retinal changes, have been reported in a few
Does tamoxifen cause other types of cancer?
Although tamoxifen can cause liver cancer in particular strains of rats, it is not
known to cause liver cancer in humans. It is clear, however, that
tamoxifen can sometimes cause other liver toxicities in patients, which
can be severe or life threatening. Doctors may order blood tests from
time to time to check liver function.
One study suggested a possible increase in cancers of the digestive tract among women receiving tamoxifen for
breast cancer. Other trials, including the BCPT, have not shown an
association between tamoxifen and these cancers.
Studies such as the BCPT show no increase in cancers other than
uterine cancer. This potential risk is being evaluated.
Should women taking tamoxifen avoid pregnancy?
Yes. Tamoxifen may make premenopausal women more fertile,
but doctors advise women on tamoxifen to avoid pregnancy because animal
studies have suggested that the use of tamoxifen in pregnancy can cause
fetal harm. Women who have questions about fertility, birth control, or pregnancy should discuss
their concerns with their doctor.
Does tamoxifen cause a woman to begin menopause?
Tamoxifen does not cause a woman to begin menopause, although it can
cause some symptoms that are similar to those that may occur during
menopause. In most premenopausal women taking tamoxifen, the ovaries continue to act normally and produce estrogen
in the same or slightly increased amounts.
Do the benefits of tamoxifen in treating breast cancer outweigh its
The benefits of tamoxifen as a treatment for breast cancer are firmly
established and far outweigh the potential risks. Patients who are
concerned about the risks and benefits of tamoxifen or any other
medications are encouraged to discuss these concerns with their doctor.
How long should a patient take tamoxifen for the treatment of breast
Patients with advanced breast cancer may take tamoxifen for varying
lengths of time, depending on their response to this treatment and other factors. When
used as adjuvant therapy for early stage breast cancer, tamoxifen is
generally prescribed for 5 years. However, the ideal length of treatment
with tamoxifen is not known.
Two studies have confirmed the benefit of taking adjuvant tamoxifen
daily for 5 years. These studies compared 5 years of treatment with
tamoxifen with 10 years of treatment. When taken for 5 years, the drug
reduces the risk of recurrence of the original breast cancer and also
reduces the risk of developing a second primary cancer in the other
breast. Taking tamoxifen for longer than 5 years is not more effective
than 5 years of therapy.