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Rubylyn T. Dela Rama

Aromatase Inhibitors
Aromatase inhibitors stop the production of estrogen in postmenopausal women.
Aromatase inhibitors work by blocking the enzyme aromatase, which turns the
hormone androgen into small amounts of estrogen in the body. This means that less estrogen is
available to stimulate the growth of hormone-receptor-positive breast cancer cells.
Aromatase inhibitors can't stop the ovaries from making estrogen, so aromatase inhibitors only
work in postmenopausal women.
There are three aromatase inhibitors:
Arimidex (chemical name: anastrozole)
Aromasin (chemical name: exemestane)
Femara (chemical name: letrozole)
Each is a pill, usually taken once a day. Arimidex and Femara are available as generic medicines.
Benefits of aromatase inhibitors
A number of studies have compared aromatase inhibitors with tamoxifen to see which type of
medicine was more effective in treating early-stage, hormone-receptor-positive breast cancer in
postmenopausal women. Based on the results, most doctors recommend that after initial
treatment (surgery and possibly chemotherapy and radiation therapy):
an aromatase inhibitor is the best hormonal therapy to start with. When treating early-
stage, hormone-receptor-positive breast cancer, aromatase inhibitors have more benefits
and fewer serious side effects than tamoxifen.
switching to an aromatase inhibitor after taking tamoxifen for 2 to 3 years (for a total of 5
years of hormonal therapy) offers more benefits than 5 years of tamoxifen.
taking an aromatase inhibitor for 5 years after taking tamoxifen for 5 years continues to
reduce the risk of the cancer coming back, compared to no treatment after tamoxifen.
Side effects of aromatase inhibitors
Aromatase inhibitors tend to cause fewer serious side effects than tamoxifen, such as blood clots,
stroke, and endometrial cancer. But aromatase inhibitors can cause more heart problems, more
bone loss (osteoporosis), and more broken bones than tamoxifen, at least for the first few years
of treatment. If you and your doctor are considering an aromatase inhibitor as part of your
treatment plan, you may want to ask your doctor about having a bone density test to see if a bone
strengthening medicine might be necessary while you're taking the aromatase inhibitor.
The most common side effects of aromatase inhibitors are joint stiffness or joint pain.
Joint pain from taking an aromatase inhibitor can be troubling. But a 2008 British study suggests
that women who experienced joint pain while taking hormonal therapy medicine were less likely
to have the breast cancer come back (recur). Knowing that this side effect might indicate a
reduced risk of the cancer coming back may help some people stick with treatment despite the
side effects.
If you're experiencing side effects from taking one aromatase inhibitor medicine, tell your
doctor. You may be able to take a different medicine. Arimidex and Femara have similar
chemical structures, while Aromasin has a different structure.



















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 a little 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?
Studies have shown that aromatase inhibitors are better than tamoxifen for treating advanced
breast cancer. 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 and
raloxifene, including hot flashes and vaginal dryness. Muscle and joint pain and headaches
happen more often.
Aromatase inhibitors seem much less likely to cause serious blood clots.
Unlike tamoxifen and raloxifene, aromatase inhibitors tend to speed up osteoporosis (bone
thinning), which can lead to broken bones.
Based on the studies done so far, they do not seem to raise the risk of endometrial cancer or
uterine sarcoma, like tamoxifen and raloxifene do.
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 not approved to be used to reduce breast cancer risk.
They are used either to treat advanced breast cancer or given after surgery (instead of or after
tamoxifen) to help prevent breast cancer from coming back. The FDA has not approved any of
these drugs to reduce the risk of developing breast cancer.
But one of these drugs has been shown to lower breast cancer risk in a clinical trial. The MAP3
study compared exemestane to placebo (sugar pill) in a large group of post-menopausal women
who had an increased risk of breast cancer.
After an average of about 3 years on the study, there were 32 cases of invasive breast cancer in
the women on placebo, while only 11 cases in the 2,285 women taking exemestane. This is a
65% lower risk in the exemestane group.
Exemestane did not have a strong effect on the risk of ductal carcinoma in situ, with 12 cases in
the placebo group versus 9 in the exemestane group.
Most side effects were mild, with the most common side effects being hot flashes and joint pain.
The women in the group treated with exemestane were not more likely to get osteoporosis or
fractures (broken bones).
Other studies are looking at the effect of aromatase inhibitors on 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. 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.









Aromatase Inhibitors for Breast Cancer
Examples
Generic Name Brand Name
anastrozole Arimidex
exemestane Aromasin
letrozole Femara
Aromatase inhibitors are available as tablets. Follow your doctor's orders or the directions on the
label.
How It Works
Aromatase inhibitors interfere with how much estrogen the body's tissues can make. This limits
the amount of estrogen available in the body.
An aromatase inhibitor cannot lower estrogen levels made by the ovaries. That is why an
aromatase inhibitor only works after menopause, when a woman's ovaries have stopped making
estrogen and other hormones.
1

Why It Is Used
Aromatase inhibitors are used to treat early estrogen receptor-positive (ER+) breast cancer. They
are also used to treat metastatic or recurrent ER+ breast cancer. An aromatase inhibitor can be
used alone or after tamoxifen treatment.
Some doctors may use aromatase inhibitors "off-label" to treat infertility and endometriosis. This
means that the U.S. Food and Drug Administration (FDA) has not approved this use.
How Well It Works
Aromatase inhibitors make it less likely that breast cancer will come back. These medicines
work well for postmenopausal women who have had ER+ breast cancer. Studies that compare
survival rates for aromatase inhibitors and tamoxifen show that women live about the same
length of time when taking either of these medicines.
2

Aromatase inhibitors may be given to postmenopausal women who have breast cancer, either at
the beginning of treatment or after they are given tamoxifen.
Side Effects
Side effects of an aromatase inhibitor may include:
Hot flashes.
Muscle or body aches.
Mild nauseaand vomiting
Joint pain
Vaginal dryness
Weakness and fatigue.
Bone thinning (osteoporosis) Aromatase inhibitors increase the rate of bone thinning
that occurs normally in postmenopausal women.
What To Think About
For breast cancer treatment, aromatase inhibitors should be given only under the supervision of a
medical oncologist






Aromatase inhibitors and breast cancer treatment
Aromatase inhibitors lower estrogen levels in the body by blocking aromatase, an enzyme that
converts other hormones into estrogen.
Like tamoxifen, aromatase inhibitors are used to treat metastatic and early breast cancers that are
hormone-receptor positive. Aromatase inhibitors include:
Anastrozole (Arimidex)
Exemestane (Aromasin)
Letrozole (Femara)
Unlike tamoxifen, aromatase inhibitors are only used to treat postmenopausal women.
Postmenopausal women with hormone receptor-positive breast cancer either begin hormone
therapy with an aromatase inhibitor or begin with tamoxifen and after a few years, switch to an
aromatase inhibitor.
Aromatase inhibitors come in a pill form and are taken every day. When aromatase inhibitors are
the only hormone therapy given, they are taken for five years. When women switch to an
aromatase inhibitor after taking tamoxifen for a few years, they take these drugs for a combined
total of at least five years. The number of years that aromatase inhibitors should be taken to get
the most treatment benefit is still under study.
Benefits of aromatase inhibitors
Treatment with an aromatase inhibitor (alone or after tamoxifen) lowers the risk of [61]:
Breast cancer recurrence
Breast cancer in the opposite breast
Death from breast cancer
Among postmenopausal women with hormone receptor-positive breast cancer, aromatase
inhibitors (alone or after tamoxifen) offer the same or slightly better treatment benefit compared
to treatment with tamoxifen alone [61,69-72]. The aromatase inhibitors anastrozole, exemestane
and letrozole all have a similar treatment benefit [61,69-72]. They also have similar side effects.
However, you may tolerate one drug better than another.

For a summary of research studies on aromatase inhibitors and early breast cancer, visit
the Breast Cancer Research section.

Side effects of aromatase inhibitors
The side effects of aromatase inhibitors differ from those of tamoxifen. Learn more about the
side effects of aromatase inhibitors.
Issues still under study
At present, we still do not know how long women should take aromatase inhibitors. There are no
data on the benefits or safety of taking aromatase inhibitors for longer than five years.
Another question is whether aromatase inhibitors benefit women who were premenopausal when
diagnosed with breast cancer, but became menopausal due to treatment. New and ongoing
studies should help answer such questions. Because aromatase inhibitors only work in
postmenopausal women, tamoxifen should be used if there is any chance you are still
premenopausal.
Aromatase inhibitors are being studied in the chemoprevention (risk-lowering drugs) setting as
well. Findings from a recent randomized controlled trial showed the aromatase inhibitor
exemestane lowered the risk of developing breast cancer in postmenopausal women at high risk
[73]. Exemestane does not yet have FDA-approval for use in the chemoprevention setting. Learn
more about chemoprevention for breast cancer.
To learn more about aromatase inhibitors, visit the National Institutes of Health's Medline Plus
website.
Importance of following your breast cancer treatment plan
The importance of adherence (compliance)
Breast cancer treatment is most effective when all parts of the treatment plan are followed.
Adherence (also called compliance) is how closely people follow the treatment plan (for
medications and other therapies) prescribed by their health care providers in terms of:
Timing
Dose
Frequency
Completing hormone therapy with aromatase inhibitors
Hormone therapy used to treat breast cancer is typically prescribed for at least five years. The
length of treatment coupled with side effects can make adherence to hormone therapy difficult.
Although the menopausal symptoms related to hormone therapy can be hard to deal with, there
are treatments that may ease these side effects. If you have side effects, talk to your health care
provider about ways to treat them.
To get the most benefit out of hormone therapy, you need to take the full course of treatment.
Women who complete the full course have higher rates of survival [63].
If you have trouble remembering to take your hormone therapy, a daily pillbox or setting an
alarm on your watch or phone may help [3]. However, you do not need to panic if you miss a day
or two.
If you have hormone receptor-positive breast cancer, hormone therapy with tamoxifen and/or an
aromatase inhibitor (such as anastrozole, letrozole and exemestane) is a key part of your
treatment.
Aromatase inhibitors are only used to treat postmenopausal women. Premenopausal women
should not take aromatase inhibitors. And, women with certain heart problems should not take
the aromatase inhibitor anastrozole.
Side effects of aromatase inhibitors versus side effects of
tamoxifen
Although both aromatase inhibitors and tamoxifen can cause menopausal symptoms such as hot
flashes and night sweats, they have many different side effects as shown below in Figure 5.11.
Your health care provider can help you treat many of these side effects.

Figure 5.11: Side effects of aromatase inhibitors versus side effects of tamoxifen
Aromatase inhibitors Tamoxifen
Common side effects
Hot flashes and night
sweats
Joint and muscle pain
Loss of bone mineral
density (may lead to
osteoporosis or bone
fractures)


Hot flashes and night
sweats
Vaginal discharge
Vaginal dryness or itching

Uncommon or rare side
effects
Carpal tunnel syndrome
Hair thinning
Heart problems
Increased blood pressure
Increased cholesterol
Mood swings and
Loss of sex drive
Vaginal bleeding
Very rare:
Blood clots in the large
veins (deep vein
depression

thrombosis)
Blood clots in the lungs
(pulmonary emboli)
Bone loss (premenopausal
women only)
Cancer of the lining of the
uterus (endometrial
cancer)
Cancer of the uterus
(uterine cancer)
Cataracts
Stroke

Adapted from National Cancer Institute materials [67,69-74].

Learn more about the side effects of tamoxifen.
Aromatase inhibitors and joint and muscle pain
Joint pain (arthralgia ar-THRAL-juh) and muscle pain (myalgia my-AL-juh) are common
side effects of aromatase inhibitors. The pain may be in the hands and wrists, feet and ankles,
knees, back or other parts of the body [75-76]. Up to 36 percent of women in clinical trials of
aromatase inhibitors have reported joint pain and up to 15 percent have reported muscle pain
(other studies have found even higher rates of these side effects) [75-77]. Although aromatase
inhibitors can cause joint and muscle pain, they do not cause permanent joint or muscle damage.
If you have joint or muscle pain while taking an aromatase inhibitor, talk to your health care
provider. Anti-inflammatory medications (such as aspirin or ibupropin), special exercises or
acupuncture may ease the pain [76,78]. Or, your provider may switch you to another aromatase
inhibitor (you may have less pain with a different drug) or recommend tamoxifen [77-78].
Aromatase inhibitors and bone health
Aromatase inhibitors cause a loss of bone density, which leads to higher rates of osteoporosis
and bone fractures compared to tamoxifen [74]. Some medications may help prevent
osteoporosis. Your health care provider may prescribe drugs called bisphosphonates or the drug
denosumab to help maintain bone density while you are taking aromatase inhibitors.
You can help strengthen and protect your bones through regular exercise [79]. For example,
weight-bearing exercise (exercise that involves standing rather than sitting) and protect bones
and lower the risk of hip fractures [80]. Getting enough calcium and vitamin D (your provider
can tell you if you are getting enough calcium and vitamin D) and not smoking can also help
strengthen your bones [79].
Although mostly a concern for people with metastatic breast cancer who take higher doses of
bisphosphonates or denosumab, these drugs can cause severe bone, joint and muscle pain
[74,81]. If you have any of these symptoms, report them to your health care provider right away.
In rare cases, a serious jaw bone disorder called osteonecrosis may occur. It is important to have
a dental exam prior to starting treatment with bisphosphonates