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Chemoprevention, the use of drugs to reduce the risk of
cancer in healthy people, is a fairly new and rapidly growing area of
cancer research. Several clinical studies have shown that the drugs
tamoxifen and raloxifene may reduce the risk of breast cancer in women
known to be at increased risk. Other studies are looking at the
effectiveness of newer drugs called aromatase inhibitors in risk
reduction.
The following information is intended to help you and your
doctor decide whether or not one of them may be right for you.
Tamoxifen (Nolvadex®)
What Is Tamoxifen?
Tamoxifen is a drug that is taken once a day 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 works by blocking
estrogen from attaching to receptors (molecules that regulate the
cells' activity) on the surface of breast cells. .For this reason,
tamoxifen is often called an "anti-estrogen" and is used as a treatment
for estrogen receptor-positive breast cancer. (Estrogen
receptor-positive breast cancer responds to estrogen, and estrogen
receptor-negative breast cancer does not.)
As a treatment for breast cancer, this drug slows or stops the
growth of estrogen receptor-positive cancer cells that are already
present in the body. Tamoxifen also helps prevent 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 Effective Is Tamoxifen in
Reducing the Risk of Developing 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 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, the other took a placebo (sugar pill), but neither group of
women knew which pill they were taking. After observing these women for
7 years, the study found that compared to the women taking the placebo,
those who took tamoxifen had:
- About half the risk of invasive breast cancer. There were
145 cases in the tamoxifen group vs. 250 cases in the placebo group.
- About one-third less risk of noninvasive breast cancer,
such as ductal carcinoma in situ (DCIS) or lobular carcinoma in situ
(LCIS). There were 60 cases in the tamoxifen group vs. 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 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 similar in design to the BCPT study. 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 to
those taking a placebo. Recent findings from the IBIS-I study also have
shown that the breast cancer risk reduction effect of tamoxifen
continues, even beyond the 5 years of actually taking the drug. In
fact, this study has shown that tamoxifen's risk-reducing effects
lasted for at least 10 years, while most of its side effects stop when
the drug is stopped.
Are There Other Benefits of
Taking Tamoxifen?
In addition to reducing the risk of developing breast cancer,
tamoxifen can also help prevent osteoporosis, or weakening of the
bones, that can occur in women after they reach menopause. The BCPT
study found that it reduced the risk of bone fractures of the hip,
wrist, and spine by about one third (32%).
Tamoxifen did not offer protection against heart attacks in
the BCPT study, although it did seem to provide some in other studies
of women who already had breast cancer. More research is needed to
clarify these conflicting results.
Are There Risks With Taking
Tamoxifen?
Tamoxifen is a complex chemical. In addition to its
anti-estrogen properties it appears 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)
- uterine sarcoma (cancer of the connective tissue of the
uterus)
- major blood clots (pulmonary embolism, stroke, deep vein
thrombosis)
Endometrial Cancer and Uterine Sarcoma
Estrogens and agents that act like estrogens are known to
increase the
risk of endometrial cancer. According to the BCPT study, tamoxifen
increases a woman's chance of developing endometrial cancer (based on
53 cases in the tamoxifen group vs. 17 cases in the placebo group of
the study). It also appears to increase the risk of developing a rare
but serious form of cancer known as uterine sarcoma (based on 3 cases
in the tamoxifen group vs. 1 case in the placebo group).
It is especially important for women who have taken or are
taking tamoxifen to discuss this information with their doctors. These
women are strongly encouraged to report any unexpected vaginal bleeding
or spotting, which could be symptoms of these cancers. Women should
talk to their doctors about the potential 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 methods currently
available for detecting endometrial cancer are the endometrial biopsy
and transvaginal ultrasound. (For more information, see the American
Cancer Society document, Endometrial
Cancer.)
Although 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, ACS makes no
recommendation for routine screening for these women. This is because
so far, studies to date 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 may lead to
unnecessary surgery to evaluate "false positive" test results.
Women who have had a hysterectomy (surgery to remove the
uterus) are not at risk for endometrial cancer.
Major Blood Clots
According to the BCPT
study, women taking tamoxifen have about 2 times the chance of
developing a pulmonary embolism, which is a blood clot in the lung.
This finding is based on 28 cases in the tamoxifen group vs. 13 cases
in the placebo group.
Women in the tamoxifen group of the study were also more
likely to have a stroke or to have deep vein thrombosis (a blood clot
in a major vein), although the differences were small enough that they
may have been due to chance.
The IBIS-I study also found an increased risk of blood clots
(about 2˝ times higher) in the women who took tamoxifen, especially
among those who had recently had major surgery. Women taking tamoxifen
who
will be having surgery may want to speak with their doctors about this.
In general, blood clots occur more often in people with high
blood pressure or diabetes, smokers, and in those who are obese.
Are There Any Other Possible
Side Effects of Tamoxifen?
Like most medicines, tamoxifen causes side effects in some
women. The side effects experienced most often by women in the BCPT
study were hot flashes and vaginal discharge. Other side effects were
also reported, but these were no more common in the women who took
tamoxifen than in the women who took placebo and included:
- vaginal dryness, itching, or bleeding
- menstrual irregularities
- depression
- loss of appetite
- nausea and/or vomiting
- dizziness
- headaches
- weight gain
- fatigue
Treatments that could reduce or eliminate most of these side
effects are available.
Some research has shown that women who take tamoxifen may be
at a slightly increased risk for developing 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. The IBIS-I
study, however, did not find an increased risk of cataracts. As women
age, they are more likely to develop cataracts whether or not they take
tamoxifen.
As in the BCPT study, women on tamoxifen in the IBIS-I study
were also more likely to have vaginal discharge and hot flashes. New
findings in the IBIS-I study included an increased risk of vaginal
yeast infections and an increased risk of having brittle nails.
Does Tamoxifen Cause a Woman to
Begin Menopause?
Tamoxifen does not cause a woman to begin menopause, although
it can cause some similar symptoms (such as hot flashes, night sweats,
mood swings, and vaginal dryness). In most premenopausal women taking
tamoxifen, the ovaries continue to act normally and produce female
hormones (estrogens) in the same or slightly increased amounts.
How Long Should Women Take
Tamoxifen?
When used to treat breast cancer, tamoxifen should be taken
for 5 years. In one study, women with early stage breast cancer who
took tamoxifen for 10 years had no greater benefit from the longer
duration and showed a trend toward more side effects.
In the BCPT study, women took tamoxifen for 5 years. The
ideal length of time women should take tamoxifen to reduce their risk
of breast cancer is not known. This question is being researched.
Recent reports from the IBIS-I study have shown that the benefits of
taking tamoxifen for 5 years may actually last beyond the 5 year active
treatment period, while the side effects do not. Based on the best
information available
at this time, it is recommended that women take the drug for 5 years.
Does Tamoxifen Have the Same
Risks as Hormone Replacement Therapy?
Hormone replacement therapy (HRT), also called
post-menopausal hormone therapy (PHT), is used by some women to reduce
hot flashes and other problems after menopause that can affect quality
of life. It may also help women maintain bone density, reduce the risk
of fractures, and may reduce the risk of colon cancer.
Clinical studies have suggested that combined HRT (estrogen
plus progesterone) increases a woman's chances of developing heart
problems, blood clots, breast cancer, and other serious health
problems. Women considering using HRT after menopause should be aware
of these potential effects and should discuss them with their doctor
before deciding on a course of action. Those who decide to use HRT
should do so at the lowest effective dose and for the shortest possible
time.
Tamoxifen, on the other hand, does not reduce menopausal
symptoms and may actually make them worse. Like HRT, it appears to
increase 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, however, is still not known.
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
- 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 determined by the Breast Cancer
Assessment Profile. Their risk score was a minimum of 1.7% meaning 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 below for information on how risk scores are determined.)
Many diseases, including breast cancer, occur more often in
older women. The risk of developing breast cancer increases with age.
This means that breast cancer occurs more commonly in women moreolder
than 60 years old compared to women in their 40s and 50s. A woman
younger than age 60 could have similarthe same risk toas a 60 year-old
woman (or even higher) if she has one or more of the following factors:
- BRCA1 or BRCA2 gene alteration
- previous history of breast cancer
- breast biopsy result that shows either atypical ductal
hyperplasia (ADH) or lobular carcinoma in situ (LCIS). These conditions
indicate an increased chance of developing invasive breast cancer
- family history of breast cancer (i.e. several close
relatives – mother, sister(s), daughter(s) – particularly if they were
diagnosed before menopause)
- not having any children, or having a first child later in
life (after age 30)
- starting menstrual periods before age 12 or going through
menopause after age 55
To learn more about your own breast cancer risk and whether
you might want to consider taking tamoxifen, see the section, "Breast Cancer Risk Assessment: Should I
Consider Taking Tamoxifen?"
Should Certain Women NOT Take
Tamoxifen for Risk Reduction?
Tamoxifen should not be used to reduce breast cancer risk in
women who:
- have ever had blood clots or who develop blood clots that
require medical treatment
- are taking medicines to thin their blood
- have a history of high blood pressure, smoking, obesity,
or diabetes -- tamoxifen increases the risk of blood clots in these
women.
- are planning to become pregnant or are pregnant
- are breast-feeding
- are younger than 35 years old, or are younger than 60
years old
and who are not at increased risk
- have not had any breast cancer risk assessment
- are currently taking hormone replacement therapy,
raloxifene or an aromatase inhibitor
There may be other reasons that a woman should not take
tamoxifen, such as a history of atypical hyperplasia of the uterus or
cataracts. Women should talk with their doctor about their specific
situation.
Tamoxifen may cause birth defects if taken at the time of
conception or during pregnancy. People taking this drug need to use a
barrier or non-hormone method of birth control. If you are pregnant,
breast-feeding, or planning to have children in the future, tell your
doctor before you start treatment. Do not use oral contraceptives
(birth control pills) or other contraceptives containing 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 consider
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 of the therapy must be carefully considered.
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 is at increased risk of breast
cancer, tamoxifen therapy may not be appropriate for her. Any woman who
is considering tamoxifen therapy should talk with her doctor about her
personal health situation in order to make the best decision for
herself.
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 participate in the BCPT study, in part because
there are known side effects of taking tamoxifen.
Women at average risk would be exposed to the same risks of
the drug, but the benefit would be less because fewer of these women
would be expected to develop breast cancer. There is currently no
recommendation to take any breast cancer chemopreventive medicine if
you are not considered to be at an increased risk. Women who are not at
increased risk should talk with their doctor about their specific
situation.
Breast
Cancer Risk Assessment: Should I Consider Taking Tamoxifen?
There is no easy answer to this question, and ultimately any
decision you make should be made with your doctor. As is the case with
almost all drugs, there are benefits and risks with taking tamoxifen.
For now, most experts feel 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 risk needs to compare the benefit
of possibly reducing her breast cancer risk with the potential for side
effects and complications 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 affects a person's chance of getting a disease. For
example, smoking is a known risk factor for lung and several other
cancers.
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. Another risk factor is
family history. If your mother or sister or aunt or grandmother has had
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 combined can influence
your risk, such as age at first menstruation and menopause and your age
when your first child was born.
Being at higher risk because of a certain characteristic or
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
following questions. 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), 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 generally low to begin with.
If 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 effective tamoxifen
would be for women in their 50s who don't have a lot of other risk
factors because those women did not take part in the study. But because
you
are close to the age cutoff, it may be OK for you to consider taking
tamoxifen. Discuss this with your doctor, particularly the risks and
benefits of taking tamoxifen and 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 sufficient to consider taking
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: Proceed
to the next question.
If yes: If
you had breast cancer including ductal carcinoma in situ, did you take
tamoxifen as part of your treatment?
If yes: Tamoxifen
should only be taken for 5 years, so you would not be a candidate for
taking tamoxifen to further reduce your risk. One of the newer
aromatase inhibitors (discussed later on) may be an option for you. You
may want to speak with 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 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 is 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 ADH
and are 35 or older: ADH by itself may not increase a
woman's risk of getting breast cancer to the level where she might
consider taking tamoxifen. However, women who have had a diagnosis of
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 a family
history of breast cancer?
If no: Proceed
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
prior to age 50 and/or ovarian cancer at any age, you may want to talk
to your doctor about your risk and whether to consider taking
tamoxifen.
If you are "positive for the breast cancer gene" or have been
told 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 consider taking tamoxifen to reduce breast
cancer risk. If you are age 35 or older this is an option for you.
As part of the follow-up to the BCPT study, the researchers
looked specifically at the effect of tamoxifen 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 not
among women with BRCA1 mutations. The number of women in both groups
was small, however, so the true impact of tamoxifen among women with
these mutations is not well understood.
QUESTION: Do you have other
breast cancer risk factors?
Other factors known to increase your risk of breast cancer
include:
- start of menstrual periods at an early age (before age
12)
- having no children, or having your first child later in
life (after age 30)
- going through menopause after age 55
If no: Most
women under age 55 who do not have a strong family history of breast
cancer, a personal history of breast cancer, or other factors are not
at high enough risk to consider taking tamoxifen based on the
information available today.
If yes: A
small percentage of women under age 55 who do not have a personal or
family history of breast cancer 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 and ask him or her to
estimate your risk of getting breast cancer.
Breast Cancer Risk Assessment
Tools
Researchers have built several different statistical models to
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 allows doctors and nurses to help
women make informed decisions about taking tamoxifen. It gives them a
risk score by calculating a woman's risk of developing breast cancer in
the next 5 years and over her lifetime, based on certain risk factors.
The tool does have some limitations, though. For example, some
doctors feel it does not count family history strongly enough. It's
also important to note that this tool was created for health
professionals, so it may contain unfamiliar terms and explanations. 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 criteria, such as
the BRCAPRO, Gail, and Claus models, can also be used to estimate 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 groups to ensure they apply
equally to all women. These tools can provide a rough estimate of risk,
but they can't predict for certain whether you will develop breast
cancer.
Eligibility for Tamoxifen vs.
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 on the basis of the Gail score.
This included all women over the age of 60, those between 35 and 59
with factors that increased their risk to this level (as described
above), and either pre- or post-menopausal women.
But not everyone who is eligible for tamoxifen would
necessarily benefit from taking it, because of its potentially serious
side effects. Since the BCPT study, researchers have attempted to look
at more than just a woman's risk of developing breast cancer in trying
to determine 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 experience a stroke or a blood
clot, which could mean tamoxifen might be riskier for them.
Recent studies estimate that about 15% of all women over the
age of 35 would be eligible to take tamoxifen to reduce their risk of
breast cancer, according to the criteria currently used by the FDA. But
only in about one third of these women would the benefit clearly
outweigh 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.
Tamoxifen to Reduce Breast
Cancer Risk: Conclusions
Scientists are working very hard to develop information about
competing risks, such as how a woman's risk of heart disease should
influence her decisions about breast cancer risk reduction. As new
information is collected, recommendations about who should and who
should not consider taking tamoxifen may change. Also remember 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 determine
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 there was no 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 similar to tamoxifen in many
ways. It is also taken daily as a pill and, like tamoxifen, it stops
breast cells from being affected by estrogen. Both of these drugs can
also help prevent osteoporosis, or weakening of the bones, that can
occur in women after they reach menopause. Raloxifene is FDA approved
to help reduce breast cancer risk in women past menopause who are at
high risk for breast cancer or who have osteoporosis. Raloxifene also
has approval to help prevent osteoporosis in post-menopausal women.
What Are the Possible Benefits
of Taking Raloxifene?
Information about raloxifene is limited compared with that on
tamoxifen because it has been studied for a shorter time and in a
smaller number of women.
One large study looked at more than 7,000 women with
osteoporosis after menopause. They took either raloxifene or a placebo
in a study called the Multiple Outcomes of Raloxifene Evaluation, or
MORE trial. Results suggested that raloxifene might also reduce breast
cancer risk. Although the study was designed to look at osteoporosis,
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 vs. 58 cases in the placebo group).
Raloxifene was also found to increase the bone density and to
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 post-menopausal women who
were at increased risk of breast cancer. They were assigned to take
either tamoxifen or raloxifene each day for 5 years.
Both drugs reduced the risk of invasive breast cancer by about
the same extent -- 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). However, the
overall number of cases was small, and the researchers noted this
difference could possibly be due to chance. 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
post-menopausal women with coronary heart disease who took either
raloxifene or placebo daily for 5 years. It found that raloxifene had
no significant 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. However,
it was also found to be associated with an increased risk of stroke and
blood clots, at rates much like those associated with tamoxifen.
Both drugs 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, a serious risk with raloxifene is blood
clots in the legs or lungs. 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.
However, 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 do so to the same extent as tamoxifen.
In most, but not all studies to date, tamoxifen therapy is
linked to higher risk of stroke. In the STAR trial the incidence of
stroke was similar 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 observed 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 potentially at risk for uterine cancer. Among these women,
there were 36% fewer cases of uterine cancer in those taking raloxifene
compared to those taking tamoxifen (23 cases vs. 36 cases). However,
the number of cases was so small that the researchers noted the
difference could possibly be due to chance. 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 (edema)
Overall, when compared to 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 developing
cataracts.
Is Raloxifene Available for
Reducing Breast Cancer Risk?
Raloxifene is approved by the FDA for breast cancer risk
reduction in women past menopause who are at high risk of breast cancer
or who have osteoporosis. It is also approved to treat osteoporosis.
Raloxifene to Reduce Breast
Cancer Risk: Conclusions
Raloxifene seems to reduce the risk of invasive breast cancer
to the same extent as tamoxifen, although 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 who are pre- or post-menopausal). Women and their doctors need to
weigh the possible benefits and risks before deciding whether or not it
is right for them.
Aromatase Inhibitors
What Are Aromatase Inhibitors?
Aromatase inhibitors are newer drugs sometimes used to treat
advanced breast cancer or to help prevent breast cancer from returning
after surgery. The drugs in this class include: exemestane (Aromasin®),
letrozole (Femara®), and anastrozole (Arimidex®).
Aromatase inhibitors work in a slightly different way than
tamoxifen and raloxifene. Instead of blocking the estrogen receptors,
they stop a key enzyme (aromatase) from converting other hormones into
estrogen. This lowers estrogen levels in the body, taking away the fuel
that estrogen receptor-positive breast cancer tumors need to grow.
These drugs are only used in post-menopausal women (women who have gone
through menopause).
What Are the Benefits and Risks
of Taking Aromatase Inhibitors?
Studies have shown that aromatase inhibitors are at least as
good as, if not better than, tamoxifen for treating advanced breast
cancer.
Several studies have found that after surgery for breast
cancer, aromatase inhibitors (used instead of or after tamoxifen) are
slightly better than tamoxifen alone at preventing breast cancer from
returning.
Some short-term effects of aromatase inhibitors can be similar
to those caused by tamoxifen, including hot flashes and vaginal
dryness. Muscle and joint pain and headaches may occur more frequently.
Aromatase inhibitors seem much less likely to cause serious
blood clots than tamoxifen. Unlike tamoxifen and raloxifene, aromatase
inhibitors appear to be more likely to cause bone fractures and speed
up osteoporosis (bone thinning). 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, the 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.
However, studies are now under way to see if aromatase
inhibitors can reduce breast cancer risk. The British IBIS-II study is
comparing anastrozole versus placebo for 5 years in 6,000
post-menopausal women at increased risk of breast cancer. The MAP3
study is comparing exemestane to placebo in a similar group of about
4,500 women at increased risk. Both of these studies are in progress,
and their results will not be available for several years. A smaller
study is also under way with letrozole.
Aromatase Inhibitors to Reduce
Breast Cancer Risk: Conclusions
Aromatase inhibitors are at least as effective as tamoxifen in
reducing the risk of the cancer coming back (recurrence) in
post-menopausal women who already have had breast cancer. They are also
used as adjuvant therapy to treat advanced breast cancer. These drugs
are currently used instead of or after tamoxifen therapy in
post-menopausal women with estrogen receptor-positive breast cancer.
Like raloxifene, aromatase inhibitors may eventually prove to
be as good as or 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 effective they may be.
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
similar to how raloxifene used for osteoporosis was found to be useful
in breast cancer therapy.) Drugs currently being researched include
aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) and
statins (drugs used to lower cholesterol).
This type of research takes many years. It will likely be some
time before meaningful results on any of these compounds are available.
Conclusion
All chemopreventive medicines have possible side effects, and
they may not be right for all women whose risk for breast cancer is
increased. If you are considering taking a chemopreventive medicine,
make sure you have a clear understanding of your breast cancer risk and
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, 1-800-ACS-2345
(1-800-227-2345), or found on our Web site, www.cancer.org.
National Organizations and Web
Sites*
In addition to the American Cancer Society, other sources of
patient information and support include:
National Cancer Institute (NCI)
Telephone: 1-800-4-CANCER (1-800-422-6237)
Internet Address: www.cancer.gov
Susan G. Komen Breast Cancer Foundation
Telephone: 1-800-IM AWARE (1-800-462-9273)
Internet Address: www.komen.org
Centers for Disease Control and Prevention (CDC)
Telephone: 1-800-232-4636
Internet address: www.cdc.gov
*Inclusion on this list does not imply endorsement
by the American Cancer Society.
The American Cancer Society is happy to address any
cancer-related topic. If you have any more questions, please call us at
1-800-ACS-2345 at any time, 24 hours a day.
References
Barrett-Connor E, Grady D, Sashegyi A, et al. Raloxifene and
cardiovascular events in osteoporotic postmenopausal women: four-year
results from the MORE (Multiple Outcomes of Raloxifene Evaluation)
randomized trial. JAMA. 2002; 287:847-857.
Barrett-Connor E, Mosca L, Collins P, et al, for the
Raloxifene Use for The Heart (RUTH) trial investigators. Effects of
raloxifene on cardiovascular events and breast cancer in postmenopausal
women. NEJM. 2006; 355(2): 125-137.
Cauley JA, Norton L, Lippman ME, Eckert S, Krueger KA, Purdie
DW, et al. Continued breast cancer risk reduction in postmenopausal
women treated with raloxifene: 4-year results from the MORE trial.
Multiple outcomes of raloxifene evaluation. Breast Cancer Res
Treat. 2001;65:125-134.
Chemoprevention: Drugs that can reduce breast cancer risk.
MayoClinic.com website. Available at:
http://www.mayoclinic.com/health/breast-cancer/WO00092. Accessed July
28, 2006.
Cuzick J. Aromatase inhibitors for breast cancer prevention. J
Clin Oncol. 2005;23:1636-1643.
Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for
prevention of breast cancer: Current status of the National Surgical
Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer
Inst. 2005;97:1652-1662.
Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M,
et al. Tamoxifen for prevention of breast cancer: Report of the
National Surgical Adjuvant Breast and Bowel Project P-1 study. J
Natl Cancer Inst. 1998;90:1371-1388.
Freedman AN, Graubard BI, Rao SR, et al. Estimates of the
number of U.S. women who could benefit from tamoxifen for breast cancer
chemoprevention. J Natl Cancer Inst.
2003;95:526-532.
Gail MH, Constantino JP, Bryant J, et al. Weighing the risks
and benefits of tamoxifen treatment for preventing breast cancer. J
Natl Cancer Inst. 1999;91:1829-1846.
IBIS Investigators. First results from the International
Breast cancer Intervention Study (IBIS-I): A randomized prevention
trial. Lancet. 2002;360:817-824.
King MC, Wieand S, Hale K, et al. National Surgical Adjuvant
Breast and Bowel Project. Tamoxifen and breast cancer incidence among
women with inherited mutations in BRCA1 and BRCA2: National Surgical
Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention
Trial. JAMA. 2001;286:2251-2256.
Kinsinger LS, Harris R, Woolf SH, Sox HC, Lohr KN.
Chemoprevention of breast cancer: a summary of the evidence for the
U.S. Preventive Services Task Force. Ann Intern Med.
2002;137:59-67.
Martino S, Cauley JA, Barrett-Connor E, et al. Continuing
outcomes relevant to Evista: Breast cancer incidence in postmenopausal
osteoporotic women in a randomized trial of raloxifene. J
Natl Cancer Inst. 2004;96:1751-1761.
Powles T, Eeles R, Ashley S, et al. Interim analysis of the
incidence of breast cancer in the Royal Marsden Hospital tamoxifen
randomized chemoprevention trial. Lancet.
1998;352:98-101.
U.S. Preventive Services Task Force. Chemoprevention of
breast cancer: Recommendations and rationale. Ann Intern Med.
2002;137:56-58.
Veronesi U, Maisonneuve P, Sacchini V, Rotmensz N, Boyle P.
Tamoxifen for breast cancer among hysterectomised women. Lancet.
2002;359:1122-1124.
Vogel VG, Costantino JP, Wickerham DL, et al. Effect 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. JAMA. 2006;295. Early
release article. Available at:
http://jama.ama-assn.org/cgi/content/full/295.23.joc60074. Accessed
June 16, 2006.
Revised: 9/14/2007
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