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What can be used to reduce the risk of
breast cancer?
When drugs are used to reduce the risk of cancer in healthy
people, it is called chemoprevention.
This is a fairly new and fast-growing area of cancer research.
Many clinical studies have shown that the drugs tamoxifen and
raloxifene may reduce the risk of breast cancer in women known to have
an increased risk. Other studies are looking at newer drugs called
aromatase inhibitors to find out if they may help reduce risk. Herbs
and dietary supplements are also being studied to find out if they
might help reduce risk.
Tamoxifen (also called Nolvadex®
or
Soltamox ™)
What is tamoxifen?
Tamoxifen is a drug that is taken once a day, most often as a
pill. It has been used for more than 25 years to help treat some women
with breast cancer.
Tamoxifen works against breast cancer, in part, by interfering
with the activity of estrogen. Estrogen is a female hormone that can
fuel the growth of breast cancer cells. Tamoxifen blocks estrogen. by
keeping it from hooking up to receptors (molecules that control the
cells' activity) on cells in the breast. For this reason, tamoxifen is
often called an anti-estrogen. It is used to treat estrogen
receptor-positive breast cancer. (Estrogen
receptor-positive breast
cancer responds to estrogen, and estrogen
receptor-negative breast
cancer does not.)
Tamoxifen has been approved by the Food and Drug
Administration (FDA) for reducing the risk of breast cancer in women
who are 35 or older, and have a higher risk of breast cancer, whether
they have gone through menopause or not. (See the section "Eligibility
for tamoxifen versus benefit from tamoxifen" for more
information.)
Tamoxifen is also approved to treat several types of breast
cancer. As a treatment for breast cancer, this drug slows or stops the
growth of estrogen receptor-positive cancer cells in the body.
Tamoxifen also helps keep cancer from coming back (recurring)
in women who have been treated for breast cancer.
Several studies also have looked at tamoxifen's ability to
lower the risk of getting breast cancer in women known to be at
increased risk for the disease.
How well does tamoxifen work to reduce the
risk of breast cancer?
The Breast Cancer Prevention Trial (BCPT), a large study
looking at tamoxifen, was sponsored by the National Cancer Institute
(NCI) in the mid 1990s. In this study, more than 13,000 women who were
at higher than average risk of breast cancer were assigned to one of
two groups. Each group was to take a pill each day for 5 years. One
group took tamoxifen and the other took a placebo (sugar pill), but
neither group of women knew which pill they were taking. After watching
these women for 7 years, the study found that, compared with the women
taking the placebo, those who took tamoxifen had:
- About half the risk of invasive breast cancer.
There were 145 cases of breast cancer in the tamoxifen group compared
with 250 cases in the placebo group.
- About one-third less risk of non-invasive breast
cancer, such as ductal carcinoma in situ (DCIS) or lobular carcinoma in
situ (LCIS). There were 60 cases in the tamoxifen group compared to 93
cases in the placebo group.
During the 7-year follow-up period, there was no major
difference in the risk of death from breast cancer between the two
groups. Breast cancer caused 11 deaths in the placebo group and 12 in
the tamoxifen group. The total number of deaths (from any cause) was
also about the same between the groups.
Another study that looked at tamoxifen for breast cancer risk
reduction, the IBIS-I study, was an international clinical trial that
began in 1992. It followed more than 7,000 women at increased risk. The
study was designed much like the BCPT study described above. After an
average of about 8 years, the women taking tamoxifen had about
one-third (34%) fewer cases of estrogen receptor-positive breast cancer
compared with those taking a placebo.
More recent findings from the IBIS-I study also have shown
that the breast cancer risk reduction effect of tamoxifen continued,
even after the 5 years the drug was actually taken. In fact, this study
has shown that tamoxifen's risk-reducing effects lasted for at least 10
years. In contrast, most of the side effects stop when the drug is
stopped.
Does taking tamoxifen have other benefits?
Along with reducing the risk of developing breast cancer,
tamoxifen can also help prevent osteoporosis, a weakening of the bones
that can happen to women after menopause. The BCPT study found that
tamoxifen reduced the risk of bone fractures of the hip, wrist, and
spine by about one third (32%).
Tamoxifen did not protect against heart attacks in the BCPT
study, but it did seem to help in other studies of women who already
had breast cancer. More research is needed to resolve these conflicting
results.
Are there risks in taking tamoxifen?
Tamoxifen is a complex drug. Along with its anti-estrogen
action, it seems to have some weak estrogen-like properties, too.
Because of this, tamoxifen may increase a woman's chance of some rare
but serious health problems such as:
- endometrial cancer (cancer of the lining of the
uterus/womb)
- uterine sarcoma (cancer of the connective tissue of
the uterus)
- major blood clots (stroke, deep vein thrombosis,
pulmonary embolism/lung clot)
Endometrial cancer and uterine sarcoma
Estrogens and agents that act like estrogens are known to
raise a women's risk of endometrial cancer. According to the BCPT
study, tamoxifen raises the risk of getting endometrial cancer (based
on 53 cases in the tamoxifen group versus 17 cases in the placebo group
of the study). It also appears to increase the risk of a rare but
serious form of cancer known as uterine sarcoma (based on 3 cases in
the tamoxifen group versus 1 case in the placebo group).
It is especially important for women who have taken or are
taking tamoxifen to talk about these cancer risks with their doctors.
These women are strongly encouraged to call their doctors to tell them
about any vaginal bleeding or spotting that is not normal. Bleeding,
spotting, or discharge could be symptoms of these cancers. Women should
also talk to their doctors about the possible benefits, risks, and
limitations of testing for early endometrial cancer detection.
Endometrial cancer usually can be found at an early stage,
when treatment is most effective. The 2 main ways to detect endometrial
cancer early are the endometrial biopsy and transvaginal ultrasound.
For more information on this topic, see our document, Endometrial
Cancer.
The American Cancer Society (ACS) recommends that women taking
tamoxifen learn about their options for endometrial cancer screening so
that they can make informed decisions. But at this time we do not
recommend routine screening for these women. This is because studies
have not shown that routine screening helps find endometrial cancer at
a more curable stage. Also, many studies have found that routine
screening for endometrial cancer can lead to unnecessary surgery to
check out false-positive test results.
Women who have had a hysterectomy (surgery to remove the
uterus) are not at risk for endometrial cancer or uterine sarcoma and
do not have to worry about these cancers.
Major blood clots
According to the BCPT study, women taking tamoxifen have about
twice the chance of developing a blood clot in the lung (called a
pulmonary embolism). This finding is based on 28 cases in the tamoxifen
group, compared to 13 cases in the placebo group.
Women in the tamoxifen group were also more likely to have a
stroke or to have a blood clot in a major vein (called a deep vein
thrombosis or DVT). But in this case, the differences were small enough
that they may have been due to chance rather than the tamoxifen.
The IBIS-I study also found a higher risk of blood clots
(about 2 times higher) in the women who took tamoxifen, especially
among those who had recently had major surgery. This risk increased
only while the woman was taking tamoxifen; it went away after the
tamoxifen was stopped. Women taking tamoxifen who will be having
surgery may want to speak with their doctors about this.
Overall, blood clots occur more often in people with high
blood pressure or diabetes, smokers, and those who are over weight
(obese).
Does tamoxifen have other possible side
effects?
Like most medicines, tamoxifen causes side effects in some
women. The side effects most often reported by women in the BCPT study
were hot flashes and vaginal discharge. There were other side effects,
but these were no more common in the women who took tamoxifen than in
the women who took placebo. They included:
- vaginal dryness, itching, or bleeding
- menstrual irregularities
- depression
- loss of appetite
- nausea and/or vomiting
- dizziness
- headaches
- weight gain
- severe tiredness (fatigue)
Treatments that could reduce or do away with most of these
side effects are available.
Some research has shown that women who take tamoxifen may have
a slightly higher risk for cataracts (a clouding of the lens of the
eye). In the BCPT study, women in the tamoxifen group were 21% more
likely to develop cataracts than women in the placebo group. They were
also more likely to have cataract surgery. But the IBIS-I study did not
find an increased risk of cataracts. As women get older, they are more
likely to develop cataracts whether or not they take tamoxifen.
As in the BCPT study, women taking tamoxifen in the IBIS-I
study were also more likely to have vaginal discharge and hot flashes.
A newer report on the IBIS-I study also found an increased risk of
vaginal yeast infections and an increased risk of having brittle nails
in women on tamoxifen.
Does taking tamoxifen make a woman start
menopause?
Tamoxifen does not cause a woman to begin menopause, but it
can cause some of the same kinds of symptoms, such as hot flashes,
night sweats, mood swings, and vaginal dryness. In most women who take
tamoxifen before menopause, the ovaries work normally and make female
hormones (estrogens) in the same or slightly increased amounts.
How long should women take tamoxifen?
When tamoxifen is used to treat breast cancer, it is most
often taken for 5 years. In one study, women with early stage breast
cancer who took tamoxifen for 10 years got no benefit from taking it
longer. They also showed a trend toward having more side effects.
In the BCPT study, women took tamoxifen for 5 years. But the
ideal length of time women should take tamoxifen to reduce their risk
of breast cancer is not known. Research is being done to try to figure
this out.
Based on the best information available at this time, most
doctors recommend that women take tamoxifen for 5 years.
Does tamoxifen have the same risks as
hormone replacement therapy?
Some women use hormone replacement therapy (HRT), also called
post-menopausal hormone
therapy (PHT),to reduce hot flashes and other
problems after menopause that can affect day-to-day living. HRT may
also help women maintain bone density and reduce their risk of
fractures.
More recent clinical studies have suggested that combined HRT
(estrogen plus progestin) raises a woman's chances of heart disease,
blood clots, breast cancer, and other serious health problems. Women
who are thinking about using HRT after menopause should know about
these possible side effects and talk to their doctors about them before
making the decision. Those who decide to use HRT should use the lowest
dose that works for the shortest possible time.
Tamoxifen, on the other hand, does not reduce symptoms linked
to menopause, and may even make them worse. Like HRT, it appears to
raise the risk of blood clots. Tamoxifen does reduce breast cancer risk
and may help slow or reduce bone loss. Its overall effect on heart
disease is still not clear.
Who should consider taking tamoxifen to
reduce their breast cancer risk?
The BCPT study looked only at women who were at increased risk
for developing breast cancer. These included:
- women 60 years of age and older, and
- women between the ages of 35 and 59 with risk
factors that increased their chances of getting breast cancer within
the next 5 years to the same level or higher than that of a 60-year-old
woman
The risk for these women was figured out by using the Breast
Cancer Assessment Profile. Their risk score was a minimum of 1.7% over
the next 5 years. This means that 17 of every 1,000 women with this
score were expected to develop breast cancer within 5 years. (See the
"Breast cancer risk assessment tools" section for information on how
risk scores are figured out.)
Many diseases, including breast cancer, happen more often in
older women. We know that breast cancer risk increases as women get
older. This means that breast cancer happens more often in women older
than 60 years old compared to women in their 40s and 50s. Still, a
woman younger than age 60 could have the same risk as a 60-year-old (or
even higher) if she has one or more of these factors:
- a BRCA1 or BRCA2 gene mutation
- has already had breast cancer
- a breast biopsy result that shows either atypical
ductal hyperplasia (ADH) or lobular carcinoma in situ (LCIS). These
conditions are signs of an increased chance of developing invasive
breast cancer.
- several close relatives--mother, sister(s),
daughter(s) with breast cancer -- especially if they were diagnosed
before menopause
- not had any children, or had a first child after
age 30
- started menstrual periods before age 12 or went
through menopause after age 55
To learn more about your own breast cancer risk and whether
you might want to talk to your doctor about taking tamoxifen, see the
section, "Breast
cancer risk assessment: Should I consider taking
tamoxifen?"
Should certain women NOT take tamoxifen to
reduce their breast cancer risk?
Tamoxifen should not be used to reduce breast cancer risk in
women who:
- have ever had blood clots or who develop blood
clots that need medical treatment
- are taking medicines to thin their blood (warfarin,
Coumadin®, heparin -- drugs that keep
blood from clotting)
- have or have had high blood pressure,obesity, or
diabetes; or have ever smoked (tamoxifen increases the risk of blood
clots in these women)
- are pregnant or planning to become pregnant
- are breast-feeding
- are younger than 35 years old
- are younger than 60 years old and are not at
increased risk
- have not had any breast cancer risk assessment
- are taking hormone replacement therapy, raloxifene,
or an aromatase inhibitor
There may be other reasons that a woman should not take
tamoxifen, such as cataracts or atypical hyperplasia of the uterus.
Women should talk with their doctors about their complete health
picture in order to make the best possible choices.
Tamoxifen may cause birth defects if it is being taken at the
time of conception or during pregnancy. Women taking this drug need to
use a barrier or another method of birth control that does not involve
hormones. If you are pregnant, breast-feeding, or planning to have
children tell your doctor before you start tamoxifen. Do not take birth
control pills (oral contraceptives) or other birth control that
contains hormones while taking this drug without checking with your
doctor first.
Should women who have an increased risk of
breast cancer take tamoxifen?
Women with an increased risk of breast cancer can think about
taking tamoxifen to reduce their risk. As with any medical procedure or
treatment, the decision to take tamoxifen is a personal one in which
the benefits and risks must be discussed with your doctor.
The balance of these benefits and risks will vary depending on
a woman's personal health history and how much importance she puts on
the benefits and risks. Even if a woman has an increased risk of breast
cancer, tamoxifen therapy may not be right for her. Any woman who is
thinking about tamoxifen therapy should talk with her doctor about her
personal health situation to make the best decision.
Should women who do NOT have an increased
risk of breast cancer take tamoxifen?
Because tamoxifen has never been studied in healthy women at
average risk for breast cancer, there's no way to know if it would
lower their breast cancer risk and if so, by how much. Only higher risk
women were allowed to take part in the BCPT study because there are
known side effects of taking tamoxifen.
Women at average risk would have the same side effects and
risks of the drug, but less benefit because fewer of these women would
be likely to develop breast cancer. There is no recommendation to take
any breast cancer chemoprevention if you are not thought to be at an
increased risk. Women who are not at increased risk may wish to talk
with their doctors about their specific situations.
Breast
cancer risk assessment: Should I
consider taking tamoxifen?
There is no easy answer to this question. As is the case with
almost all drugs, there are benefits and risks with taking tamoxifen.
For now, most experts say that a woman's breast cancer risk
should be higher than average for her to consider taking tamoxifen. A
woman who is at higher than average breast cancer risk needs to compare
the benefit of possibly reducing her breast cancer risk with the risk
of side effects and problems from taking tamoxifen.
To find out if you are at higher than average risk for breast
cancer, your risk factors need to be identified. A risk factor is
anything that is linked to a higher chance of getting a disease. For
example, smoking is a known risk factor for lung and many other
cancers. But keep in mind that not all risk factors actually play a
part in causing the cancer, and some risk factors cannot be changed.
Age is the major risk factor for breast cancer. The risk
increases as you get older. If you are 60 years old you have a higher
risk of having breast cancer than if you are 40. But older women seem
to have more of the serious side effects of tamoxifen. In studies, the
greatest breast cancer risk reduction with the fewest side effects was
seen in younger women who were at higher risk for breast cancer. For
more, see the section "Eligibility
for tamoxifen versus benefit from
tamoxifen."
Another risk factor is family history. If your mother or
sister or aunt or grandmother has had breast cancer, or you have a male
relative with breast cancer, then you have a higher risk than if you
don't have any close relatives with breast cancer. There are other risk
factors for breast cancer that are less important, but when they are
combined they can influence your risk. Examples of these risk factors
are age at first menstruation, age at menopause, and age when your
first child was born.
Having a higher risk because of a certain risk factor does not
mean that you will develop breast cancer. In fact, most women who have
one or more risk factors will never develop breast cancer.
You can get some idea about your risk of breast cancer (and
whether tamoxifen might be an option for you) by answering the
questions that follow. These are the same questions that doctors asked
women interested in taking part in the BCPT study. The questions deal
with age; personal history of breast cancer, LCIS (lobular carcinoma in
situ), DCIS (ductal carcinoma in situ), or ADH (atypical ductal
hyperplasia); reproductive history; and family history.
QUESTION: How old are you?
If you are
younger than 35 years of age: Tamoxifen is not
approved for breast cancer risk reduction in women younger than age 35.
Women in this age group were not part of the BCPT study because their
risk is low to begin with.
If you are 35-55
years of age: Go to the next question.
If you are in
your late 50s: When the BCPT study was set up,
it was decided that all women 60 and older automatically qualified to
take part. This is because breast cancer risk increases with age. The
study later showed that tamoxifen appeared to reduce breast cancer risk
by about half for women age 60 and older.
Tamoxifen is approved for breast cancer risk reduction in all
women over the age of 60, but we don't know how well tamoxifen would
work for women in their 50s unless they have other risk factors. But
because you are close to the age cutoff, it may be OK for you to take
tamoxifen. Talk to your doctor about this, particularly the risks and
benefits of taking tamoxifen, along with your personal risks for blood
clots and osteoporosis, as well as breast cancer and endometrial
cancer.
If you are 60 or
older: Most doctors consider an average
woman's risk at age 60 to be high enough to take tamoxifen to reduce
breast cancer risk, so this is an option for you. When the BCPT study
was set up, it was decided that all women 60 and older (regardless of
any other risk factor) automatically qualified to take part because
breast cancer risk increases with age. Tamoxifen was shown to reduce
breast cancer risk by about half for women age 60 and older.
QUESTION: Have you ever had breast cancer,
lobular carcinoma in situ or atypical ductal hyperplasia?
If no: Go
to the next question.
If yes: If
you had breast cancer including ductal carcinoma in
situ (DCIS), did you take tamoxifen as part of your treatment?
If yes: Tamoxifen
should only be taken for 5 years, so
tamoxifen would not be expected to reduce your risk any further. One of
the newer aromatase inhibitors may be an option for you. (We will talk
about these later on.) You may want to ask your doctor about this.
If no: The BCPT
study did not include women who had breast
cancer (or DCIS) in the past. Talk to your doctor about whether taking
tamoxifen to reduce your risk is an option for you now.
If you had
lobular carcinoma in situ (LCIS) and are 35 or
older: Doctors consider the breast cancer risk of women
who have had
LCIS to be high enough to consider taking tamoxifen, so this may be an
option for you. When the BCPT study was set up, it was decided that any
woman with LCIS automatically qualified to take part because LCIS is a
risk factor for breast cancer.
If you had
atypical ductal hyperplasia (ADH) and are 35 or
older: ADH by itself may not raise a woman's risk of
getting breast
cancer to the level where she might consider taking tamoxifen. But
women who have had ADH and who also have other risk factors may have a
risk that is high enough to consider taking tamoxifen. Talk to your
doctor about all of your risk factors and how they affect your risk, so
you can make an informed decision about whether or not to take
tamoxifen.
QUESTION: Do you have family members who
have had breast cancer?
If no: Go
to the next question.
If yes and you
are age 35 or older: When the BCPT study was
set up, it was decided that any woman age 35 and older with at least 3
close relatives who have had breast cancer automatically qualified
because a strong family history is a risk factor for breast cancer. A
close relative was defined as a mother, sister, or daughter for the
purposes of that study.
If you have grandmothers, aunts, and/or first cousins who are
all related (for example, all on one side of the family and related by
blood rather than marriage) and who were diagnosed with breast cancer
before age 50 and/or ovarian cancer at any age, or male relatives with
breast cancer, you may want to talk to your doctor about your risk and
whether or not you should take tamoxifen.
If you have been
told you are "positive for the breast cancer
gene" or that you have a mutation (change) in one of the breast cancer
genes (BRCA1 or BRCA2): The breast cancer risk of women
who have had a
genetic test result that shows a mutation (change) in the BRCA1 or
BRCA2 gene is high enough to take tamoxifen to reduce breast cancer
risk. If you are age 35 or older this may be an option for you.
As part of the follow-up to the BCPT study, the researchers
looked at how well tamoxifen worked on women in the study with BRCA1 or
BRCA2 mutations. They found that tamoxifen seemed to reduce breast
cancer risk among BRCA2 carriers by about 60%. But it did not change
breast cancer risk among women with BRCA1 mutations. Still, the number
of women in both groups was small, and the true impact of tamoxifen
among women with these mutations is not well understood.
QUESTION: Do you have other breast cancer
risk factors, such as:
- starting menstrual periods before age 12
- having no children, or having your first child
after age 30
- going through menopause after age 55
If no: Based
on what is known today, most women under age 55
who do not have breast cancer in the family, have never had breast
cancer themselves, or who don't have other risk factors are not at high
enough risk to take tamoxifen.
If yes:
A few women under age 55 who have not had breast
cancer themselves and do not have it in their families may have a
combination of risk factors that would put them in a higher risk
category. If you think this might be true for you, then talk to your
doctor about your risk of getting breast cancer.
Breast cancer risk assessment tools
Researchers have built several different statistical models to
help predict a woman’s risk of getting breast cancer.
The Risk Disk is a tool designed for health professionals
based on the questions above. It is a tool that doctors and nurses can
use to help women make informed decisions about taking tamoxifen. It
gives a risk score by calculating a woman's risk of getting breast
cancer in the next 5 years and over her lifetime.
The tool does have some limits, though. For instance, some
doctors say it does not count family history enough. It's also
important to note that this tool was created for health professionals,
so it may use terms and explanations that patients may not understand.
Ask your doctor about using this tool to give you a better idea about
your risks and whether you should consider taking tamoxifen.
Other risk tools based on slightly different risk factors,
such as the BRCAPRO, Gail, and Claus models, are also used to estimate
breast cancer risk.
None of these tools is perfect. Each has its strengths and
weaknesses, and a woman's risk may vary depending on the tool used.
Many tools have not been tested on minority women, so they may not work
the same for everyone. These tools can give you a rough estimate of
risk, but they can't predict for sure if you will develop breast
cancer.
Eligibility
for tamoxifen versus benefit
from tamoxifen
Based largely on the results of the BCPT study, the Food and
Drug Administration (FDA) approved tamoxifen to reduce the risk of
breast cancer in women whose risk of developing the disease was at
least 1.67% within the next 5 years based on the Gail score. This
included all women over the age of 60, as well as those between 35 and
59 with factors that increased their risk to this level, whether or not
they had gone through menopause.
But because of its possible serious side effects, not everyone
who meets the FDA requirements for taking tamoxifen would necessarily
benefit from it. Since the BCPT study, researchers have tried to look
at more than just a woman's risk of developing breast cancer when
trying to decide whether she might benefit. For example, older women
are at higher risk of breast cancer than are younger women, which could
mean tamoxifen might be more likely to reduce this particular risk. But
older women are also more likely to have a stroke or blood clot, which
could mean tamoxifen might be riskier for them.
Recent studies estimate that about 3 out of 20 (15%) women
over the age of 35 would be eligible to take tamoxifen to reduce their
risk of breast cancer, according to the FDA criteria. But only about 1
in 3 of these eligible women would have benefits that clearly
outweighed the risk. Generally speaking, younger women at high risk
appear to have a better benefit-to-risk ratio from tamoxifen than do
older women. But it's important to remember that each woman is unique,
and the possible benefits and risks for her depend on many factors.
The final word (for now) on tamoxifen to
reduce breast cancer risk
Scientists are working very hard to develop information about
competing risks, such as how a woman's risk of heart disease should
affect her decisions about breast cancer risk reduction. As new
information comes in, recommendations about who should and who should
not take tamoxifen may change. Also keep in mind that your risk changes
over time -- with age, with a new diagnosis of breast cancer in your
family, or if you have a breast biopsy.
Some experts think that more research is needed to learn more
about the benefits and risks of tamoxifen for breast cancer risk
reduction. The BCPT study showed the risk of getting breast cancer was
reduced by almost half, but after 7 years of research, this did not
translate into any effect on deaths from breast cancer. Other, smaller
studies have not found as strong a benefit for tamoxifen. More research
is needed to answer the many questions about using tamoxifen to reduce
the risk of breast cancer.
Raloxifene (Evista®)
What is raloxifene?
Raloxifene is a drug that is like tamoxifen in many ways. It
is a pill that is taken each day. Like tamoxifen, it stops breast cells
from being affected by estrogen. Both drugs can also help prevent
osteoporosis, or weakening of the bones, that can happen in women after
they reach menopause.
Raloxifene is approved by the FDA to help reduce breast cancer
risk in women past menopause who are at high risk for breast cancer.
Raloxifene is also approved to help prevent and treat osteoporosis in
women past menopause, even those who do not have a higher risk of
breast cancer.
What are the possible benefits of taking
raloxifene?
Information about raloxifene is limited compared with that on
tamoxifen. It has been studied for a shorter time and in fewer women.
One large study looked at more than 7,000 women with
osteoporosis after menopause. Half took raloxifene and half took
placebo (a sugar pill) in a study called the Multiple Outcomes of
Raloxifene Evaluation, or MORE trial. Although the study was designed
to look at osteoporosis, results suggested that raloxifene might also
reduce breast cancer risk. After 8 years there were fewer breast cancer
cases in the women taking the drug than in those taking the placebo (40
cases in the raloxifene group versus 58 cases in the placebo group).
Raloxifene was also found to make bones stronger and reduce
the risk of certain types of bone fractures.
A larger study, known as the STAR (Study of Tamoxifen and
Raloxifene) trial, included more than 19,000 women past menopause who
were at increased risk of breast cancer. Half were assigned to take
tamoxifen and half were assigned to take raloxifene each day for 5
years.
Both drugs reduced the risk of invasive breast cancer about
the same -- there were 163 breast cancers in the tamoxifen group and
168 cases in the raloxifene group. But raloxifene did not seem to
reduce the risk of non-invasive cancers (DCIS and LCIS) the same way
tamoxifen did. There were fewer cases of non-invasive cancers in the
tamoxifen group (57) than in the raloxifene group (80). Still, the
overall number of cases was small, and the researchers noted this
difference may be due to chance rather than the treatment itself. It is
not yet clear what this result might mean.
Another study, called the Raloxifene Use for the Heart (RUTH)
trial, was designed to look at the effect of this drug on the heart and
on invasive breast cancer. The RUTH trial looked at 10,101 women past
menopause with coronary heart disease who took either raloxifene or
placebo daily for 5 years. It found that raloxifene did not have a
major effect on the risk of coronary events (death from heart problems,
non-fatal heart attacks, or hospitalization for other heart problems),
and it reduced the risk of invasive breast cancer. But the women who
took raloxifene had higher rates of stroke and blood clots, much like
those seen with tamoxifen.
Both raloxifene and tamoxifen have been found to reduce the
risk of bone fractures to the same extent.
What are the possible risks of taking
raloxifene?
While raloxifene can cause side effects, there may be less
risk of certain serious side effects than with tamoxifen.
Major blood clots
As with tamoxifen, blood clots in the legs or lungs are a
serious risk with raloxifene. In the MORE and RUTH trials, the number
of blood clots in the lungs or legs in women taking raloxifene was
slightly higher than in those getting the placebo.
But in the STAR trial, the women taking raloxifene had 30%
fewer blood clots than those taking tamoxifen (100 cases vs. 141
cases). So while raloxifene may raise this risk slightly, it
doesn’t seem to raise it as much as tamoxifen.
In most, but not all studies to date, tamoxifen therapy is
linked to higher risk of stroke. In the STAR trial the risk of stroke
was much the same in the raloxifene and tamoxifen groups.
Uterine cancers
In the MORE trial, the women taking raloxifene were not more
likely to get endometrial cancer, a serious side effect of tamoxifen.
But very few endometrial cancers were seen in either the women taking
the drug or those taking the placebo, and not all of the women were
examined for this type of cancer.
About half of the women in the STAR trial still had a uterus
and were at possible risk for uterine cancer. Among these women, there
were 36% fewer cases of uterine cancer in those taking raloxifene
compared with those taking tamoxifen (23 cases versus 36 cases). But
the number of cases was so small that the researchers thought the
difference may be due to chance rather than the drugs. It is not clear
if raloxifene increases the risk of uterine cancer overall, but if it
does, the increase may be less than that seen with tamoxifen.
The RUTH trial found that raloxifene had no effect on the risk
of any cancer other than breast cancer.
Other side effects
In clinical trials, other effects reported in some women
taking raloxifene included:
- hot flashes
- vaginal dryness or irritation
- leg cramps
- flu-like symptoms
- swelling in the hands or feet
Overall, when compared with tamoxifen, raloxifene has not been
found to have a strong effect on the risk of heart attacks or strokes
in any of the major studies done to date. Raloxifene also seems to be
less likely than tamoxifen to increase the risk of cataracts.
Is raloxifene available for reducing breast
cancer risk?
Raloxifene is approved by the FDA to reduce breast cancer risk
in women past menopause who are at high risk of breast cancer or who
have osteoporosis. It is also approved to treat osteoporosis in women
with average breast cancer risk.
Raloxifene to reduce breast cancer risk: a
few differences
Raloxifene seems to reduce the risk of invasive breast cancer
as well as tamoxifen, but it may not reduce the risk of non-invasive
cancers (DCIS and LCIS) to the same degree. It may pose less risk than
tamoxifen in terms of some side effects, such as uterine cancers and
blood clots, but it is not without risk. Raloxifene is only used in
women who have gone through menopause. (Tamoxifen can be used by women
before or after menopause.) Women need to talk to their doctors and
weigh the possible benefits and risks before deciding whether or not
raloxifene is right for them.
Aromatase inhibitors
What are aromatase inhibitors?
Aromatase inhibitors are newer drugs that are sometimes used
to treat breast cancer or help keep breast cancer from coming back
after surgery. The drugs in this class include:
- exemestane (Aromasin®)
- letrozole (Femara®)
- anastrozole (Arimidex®)
Aromatase inhibitors work slightly differently than tamoxifen
and raloxifene. Instead of blocking the estrogen receptors, they stop a
key enzyme (called aromatase) from changing other hormones into
estrogen. This lowers estrogen levels in the body, taking away the fuel
that estrogen receptor-positive breast cancers need to grow. These
drugs are only used in women who have already gone through menopause.
What are the benefits and risks of taking
aromatase inhibitors?
For treating advanced breast cancer, studies have shown that
aromatase inhibitors are at least as good as, if not better than,
tamoxifen. For keeping breast cancer from coming back after surgery,
several studies have found that aromatase inhibitors (used instead of
or after tamoxifen) are slightly better than tamoxifen alone.
Some short-term effects of aromatase inhibitors are much like
those caused by tamoxifen, including hot flashes and vaginal dryness.
Muscle and joint pain and headaches may happen more often.
Aromatase inhibitors seem much less likely to cause serious
blood clots than tamoxifen. Unlike tamoxifen and raloxifene, aromatase
inhibitors are more likely to speed up osteoporosis (bone thinning) and
cause more broken bones. Based on the few studies done so far, they do
not seem to raise the risk of endometrial cancer or uterine sarcoma,
like tamoxifen does.
Because these drugs have been available for a shorter period
of time, much less is known about other possible long-term effects they
may have, such as on the risk of heart disease. Future research will
help define these effects.
Are aromatase inhibitors approved for use in
reducing breast cancer risk?
At this time, no. Aromatase inhibitors are used either to
treat advanced breast cancer or given after surgery (instead of or
after tamoxifen) to help prevent breast cancer from returning. The FDA
has not approved any of these drugs to reduce the risk of developing
breast cancer.
But studies are now being done to see if aromatase inhibitors
can reduce breast cancer risk. The British IBIS-II study is comparing
anastrozole to placebo for 5 years in 6,000 post-menopausal women who
are at increased risk of breast cancer. Results are expected in 2012.
The MAP3 study is comparing exemestane to placebo in a similar group of
about 4,500 women at increased risk. Results should be available in
late 2010. Smaller studies are also being done with letrozole.
Aromatase inhibitors to reduce breast cancer
risk: More research is needed
Like raloxifene, aromatase inhibitors may some day prove to be
as good as or even better than tamoxifen in reducing breast cancer
risk, but more study results will be needed to show this. Much less is
known about the possible long-term effects of these drugs. Even if they
are shown to reduce risk, each woman and her doctor will still need to
weigh the possible benefits and risks when deciding if one of them is
right for her.
Other compounds being studied
Some other medicines, such as bexarotene, lovastatin, and
deslorelin, are in early stage clinical trials for breast cancer
chemoprevention. It is not yet clear how well they may work to reduce
breast cancer.
A few dietary supplements are also being studied to look at
their possible role in reducing breast cancer risk. These include
grapeseed extract, folate, omega-3 fatty acids, and vitamins B6 and
B12.
Other clinical trials are looking at breast cancer reduction
as an unintended effect of drugs used for other reasons. (This is how
raloxifene used for osteoporosis was found to be useful in breast
cancer therapy.) Drugs currently being researched include aspirin,
other non-steroidal anti-inflammatory drugs (NSAIDs), and statins
(drugs used to lower cholesterol).
This type of research takes many years. It will probably be
some time before meaningful results on any of these compounds are
available.
What does all of this mean for you?
All chemoprevention has possible side effects. And these drugs
may not be right for all women who have an increased risk for breast
cancer. If you are thinking about taking one of them, make sure you
have a clear understanding of your breast cancer risk, as well as the
potential benefits and side effects of these medicines. Your doctor can
help you gather information and make the decision about whether or not
chemoprevention is the right choice for you.
Additional resources
More information from your American Cancer
Society
The following information may also be helpful to you. These
materials may be ordered from our toll-free number or found on our Web
site.
- Breast Cancer Dictionary (also available in Spanish)
National organizations and Web sites*
In addition to the American Cancer Society, other sources of
patient information and support include:
Facing Our Risk of Cancer Empowered (FORCE)
Toll-free number: 1-866-824 RISK (1-866-824-7475)
Web site: www.facingourrisk.org
Hereditary Cancer Center (HCC)
Toll-free number: 1- 800-648-8133
Web site: medicine.creighton.edu/hcc
National Cancer Institute (NCI)
Toll-free number: 1-800-422-6237 (1-800-4-CANCER )
Web site: www.cancer.gov
National Women's Health Information Center (NWHIC)
Toll-free number: 1- 800-994-9662
Web site: www.womenshealth.gov
Prevent Cancer Foundation (PCF)
Toll-free number: 1-800-227-2732
Web site: www.preventcancer.org
Susan G. Komen for the Cure
Toll-free number: 1-877-GO KOMEN (1- 877-465-6636)
Web site: www.komen.org
Centers for Disease Control and Prevention (CDC)
Toll-free number: 1-800-232-4636 (1-800-CDC-INFO)
TTY: 1-888-232-6348
Web site: www.cdc.gov
*Inclusion on
this list does not imply endorsement by the
American Cancer Society.
No matter who you are, we can help. Contact us anytime, day or
night, for information and support. Call us at 1-800-ACS-2345
(1-800-227-2345)
or visit www.cancer.org.
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Last Medical Review: 08/22/2008
Last Revised: 08/22/2008
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