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Tamoxifen: Questions and Answers
Key Points
- Tamoxifen (Nolvadex®) is a drug that interferes with the activity
of estrogen, a female hormone. Tamoxifen has been used for more than
30 years to treat breast cancer in women and men (see
Question 1).
- Tamoxifen has been used for almost 10 years to reduce the risk of
breast cancer in women who are at increased risk of developing breast
cancer (see Question 1).
- The known, serious side effects of tamoxifen are blood clots, strokes,
uterine cancer, and cataracts. Other side effects include menopause-like
symptoms such as hot flashes, vaginal dryness, joint pain, and leg cramps
(see Questions 4-8).
- The benefits of tamoxifen as a treatment for breast cancer are firmly
established and far outweigh the potential risks (see
Question 11).
- The results of the Breast Cancer Prevention Trial (BCPT) showed a
reduction in diagnoses of invasive breast cancer among women who took
tamoxifen for 5 years (see Question 12).
- The results of the Study of Tamoxifen and Raloxifene (STAR)
clinical trial showed that tamoxifen and another drug, raloxifene, are
equally effective in reducing invasive breast cancer risk in postmenopausal
women who are at increased risk of the disease (see Question
14).
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- What is tamoxifen?
Tamoxifen (Nolvadex®) is a drug, taken orally as a tablet, which interferes
with the activity of estrogen, a female hormone. Estrogen can promote the
development of cancer in the breast. Tamoxifen is approved by the U.S. Food
and Drug Administration (FDA) for the prevention of breast cancer and for
the treatment of breast cancer, as well as other types of cancer.
Tamoxifen has been used for more than 30 years to treat breast cancer in
women and men. Tamoxifen is used to treat patients with early-stage breast
cancer, as well as those with metastatic breast cancer (cancer that has
spread to other parts of the body). As adjuvant therapy (treatment given
after the primary treatment to increase the chances of a cure), tamoxifen
helps prevent the original breast cancer from returning and also helps prevent
the development of new cancers in the other breast. As treatment for metastatic
breast cancer, the drug slows or stops the growth of cancer cells that are
present in the body.
Tamoxifen has been used for almost 10 years to reduce the risk of breast
cancer in women who are at increased risk of developing breast cancer. Tamoxifen
is also used to treat women with ductal carcinoma in situ (DCIS), a noninvasive
condition that sometimes leads to invasive breast cancer.
- How does tamoxifen work?
Estrogen can promote the growth of breast cancer cells. Some breast cancers
are classified as estrogen receptor-positive (also known as hormone sensitive),
which means that they have a protein to which estrogen will bind. These
breast cancer cells need estrogen to grow. Tamoxifen works against the effects
of estrogen on these cells. It is often called an antiestrogen or a SERM
(Selective Estrogen Receptor Modulator).
Studies have shown that tamoxifen is only effective in treating estrogen
receptor-positive breast cancers. Therefore, the tumor’s hormone receptor
status should be determined before deciding on treatment options for breast
cancer.
Although 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 a decreased risk of osteoporosis.
- How long should a patient take tamoxifen for the
treatment of breast cancer?
Patients with metastatic breast cancer may take tamoxifen for varying lengths
of time, depending on the cancer’s 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. When taken for 5 years, tamoxifen reduces the chance of the
original breast cancer coming back in the same breast or elsewhere. It also
reduces the risk of developing a second primary cancer in the other breast.
Clinical trials are ongoing to determine whether hormone therapy taken
for more than 5 years is beneficial. These studies usually include aromatase
inhibitors (AIs) (another type of antiestrogen) (see Question 15). For example,
the National Cancer Institute (NCI), a part of the National Institutes of
Health, is sponsoring the National Surgical Adjuvant Breast and Bowel Project
(NSABP) B–42 trial. This trial is studying the AI letrozole (Femara®)
to find out how well it works compared with a placebo in treating postmenopausal
women who have received hormone therapy for hormone receptor-positive breast
cancer. More information is available in PDQ®, the NCI’s comprehensive
cancer information database, at http://www.cancer.gov/clinicaltrials/NSABP-B-42
on the Internet.
The MA–17R trial, which is being coordinated by the National Cancer
Institute of Canada’s Clinical Trials Group, is comparing letrozole
with placebo in women previously diagnosed with primary breast cancer who
participated in another clinical trial of letrozole. Information about the
MA–17R trial can be found at https://www.swogstat.org/ROS/ROSBooks/Fall%202006/Intergroup/NCIC%20CTG/JMA17R.pdf
on the Internet.
- What are some of the more common side effects of
tamoxifen?
The known, serious side effects of tamoxifen are blood clots, strokes,
uterine cancer, and cataracts (see Questions 5–8).
Other side effects of tamoxifen are similar to 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 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 blood clots or stroke?
Data from large clinical trials 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 replacement therapy.
The Breast Cancer Prevention Trial (BCPT), a large research study funded
by the NCI, was designed to test the usefulness of tamoxifen in preventing
breast cancer in women with an increased risk of developing this disease
(see Question 12). This study also found that women who
took tamoxifen had an increased chance of developing blood clots and an
increased chance of stroke (1, 2).
- 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.
Endometrial Cancer
Studies have found the risk of developing endometrial cancer to be about
2 cases per 1,000 women taking tamoxifen each year compared with 1 case
per 1,000 women taking placebo (1, 2).
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 life-threatening.
Uterine Sarcoma
Studies have found the risk of developing uterine sarcoma to be slightly
higher in women taking tamoxifen compared with women taking placebo. However,
it was less than 1 case per 1,000 women per year in both groups (1,
2). Research to date indicates that uterine sarcoma
is more likely to be diagnosed at later stages than endometrial cancer,
and may therefore be harder to control and more
life-threatening than endometrial cancer.
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 exams.
- Does tamoxifen cause other types of cancer?
Tamoxifen is not known to cause any types of cancer in humans other than
endometrial cancer and uterine sarcoma.
- Does tamoxifen cause eye problems?
As women age, they are more likely to develop cataracts (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 patients.
- Should women taking tamoxifen avoid pregnancy?
Yes. Doctors advise women receiving tamoxifen to avoid pregnancy because
animal studies have suggested that the use of tamoxifen during pregnancy
can cause harm to the fetus. 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 risks?
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.
- Can tamoxifen prevent breast cancer?
Research has shown that when tamoxifen is used as adjuvant therapy for
early-stage breast cancer, it reduces the chance that the original breast
cancer will come back in the same breast or elsewhere. It also reduces the
risk of developing new cancers in the other breast. Based on these findings,
the NCI funded the BCPT to determine whether taking tamoxifen for at least
5 years can prevent breast cancer in women who have never been diagnosed
with breast cancer but who are at increased risk of developing the disease.
This study found a reduction in diagnoses of invasive breast cancer among
women who took tamoxifen for 5 years. Women who took tamoxifen also had
fewer diagnoses of noninvasive breast tumors, such as DCIS or lobular carcinoma
in situ (LCIS) (1). After 7 years of follow-up, researchers
found similar results (2). The study found that tamoxifen
reduced the occurrence of estrogen receptor-positive tumors by 69 percent,
but no difference in the occurrence of estrogen receptor-negative tumors
was seen (1). More information about the BCPT is available
on the NCI’s BCPT home page at http://www.cancer.gov/clinicaltrials/digestpage/BCPT
on the Internet.
- Who should take tamoxifen to reduce breast cancer
risk?
The decision to take tamoxifen is an individual one. A woman and her doctor
must carefully consider the benefits and risks of therapy. At this time,
there is no evidence that tamoxifen has a net benefit for women who do not
have an increased risk of developing breast cancer.
- What is raloxifene and how does it compare to tamoxifen?
Raloxifene is a drug approved by the FDA for the prevention and treatment
of osteoporosis in postmenopausal women. Raloxifene is also approved by
the FDA for reducing the risk of invasive breast cancer in postmenopausal
women with osteoporosis and in postmenopausal women at high risk for invasive
breast cancer.
The NCI funded the Study of Tamoxifen and Raloxifene (STAR), a clinical
trial comparing raloxifene (Evista®) with tamoxifen in preventing breast
cancer in postmenopausal women who are at an increased risk of developing
the disease. The study found that raloxifene and tamoxifen are equally effective
in reducing invasive breast cancer risk in postmenopausal women who are
at increased risk of the disease. The study also found that women who took
raloxifene had fewer uterine cancers and fewer blood clots than the women
who took tamoxifen (3). However, raloxifene did not reduce
the risk of noninvasive breast tumors such as DCIS and LCIS (3).
Other side effects associated with raloxifene were similar to tamoxifen
and included hot flashes, vaginal dryness, joint pain, and leg cramps. Studies
of raloxifene to date have only examined its role in breast cancer prevention,
not treatment.
More information about STAR is available on the NCI’s STAR home page
at http://www.cancer.gov/star on
the Internet.
- What other hormone therapy may be used for early-stage
breast cancer?
Aromatase inhibitors (AIs) are another adjuvant treatment option for some
women with early-stage breast cancer. AIs block the action of a protein
called aromatase, which helps the body produce estrogen. Most of the estrogen
in a woman’s body is made in the ovaries, but other tissues can also
produce this hormone. AIs are usually used in women who have reached menopause,
when the ovaries are no longer producing estrogen.
Although AIs and tamoxifen both help to prevent the growth of estrogen-sensitive
breast tumors, they work differently in the body. Tamoxifen blocks the tumor’s
ability to use estrogen, and AIs reduce the amount of estrogen in the body.
Anastrozole (Arimidex®), exemestane (Aromasin®), and letrozole (Femara®)
are AIs that have been approved by the FDA.
The American Society of Clinical Oncology (ASCO) recommends that postmenopausal
women with hormone-sensitive breast cancer consider one of two adjuvant
treatment options (4):
• Begin treatment with tamoxifen for 2 to 3 years or 5 years, and
then switch to an AI for another 2 to 3 years or 5 years.
• Forego tamoxifen entirely and begin adjuvant treatment with an AI
for 5 years.
ASCO concluded that AIs are appropriate as initial treatment for women
who should not take tamoxifen and that patients who cannot take AIs should
receive tamoxifen.
Whether an individual patient should start therapy with an AI or begin
therapy with tamoxifen and then change to an AI is a subject of medical
judgment and clinical research. Patients should talk with their doctors
about which drug would be best for them given their particular medical situation.
Question 3 includes information about ongoing clinical trials involving
AIs to treat postmenopausal women with hormone receptor-positive breast
cancer.
Selected References
- Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen
for prevention of breast cancer: Report of the National Surgical Adjuvant
Breast and Bowel Project P-1 Study. Journal of the National Cancer Institute
1998; 90(18):1371–1388.
- Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen
for the prevention of breast cancer: Current status of the National Surgical
Adjuvant Breast and Bowel Project P-1 Study. Journal of the National Cancer
Institute 2005; 97(22):1652–1662.
- Vogel VG, Costantino JP, Wickerham DL, et al. Effects
of tamoxifen vs raloxifene on the risk of developing invasive breast cancer
and other disease outcomes: The NSABP Study of Tamoxifen and Raloxifene (STAR)
P-2 Trial. Journal of the American Medical Association 2006; 295(23):2727–2741.
- Winer EP, Hudis C, Burstein HJ, et al. American Society
of Clinical Oncology technology assessment on the use of aromatase inhibitors
as adjuvant therapy for postmenopausal women with hormone receptor-positive
breast cancer: Status report 2004. Journal of Clinical Oncology 2005;
23(3):619–629.
# # #
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