Aromatase inhibitors

Aromatase inhibitors, or AIs, are a class hormonal therapy medicines that are FDA-approved to treat hormone receptor-positive breast cancer in postmenopausal women. Hormonal therapy is also called endocrine therapy.

In early-stage breast cancer, aromatase inhibitors are used to reduce the risk of recurrence (breast cancer returning). In some cases, they may be used before surgery to shrink the cancer before surgery.

In metastatic breast cancer, aromatase inhibitors can be used on an ongoing basis.

Three aromatase inhibitors are FDA approved to treat all stages of breast cancer in postmenopausal women:

• Anastrozole (Arimidex)
• Exemestane (Aromasin)
• Letrozole (Femara)

Aromatase inhibitors can also be used to treat hormone receptor-positive breast cancer in:

• Pre- or perimenopausal women who are also taking medicines to suppress ovarian function (GnRH agonists) or who have had their ovaries removed (oophorectomy) to reduce estrogen in the body
• Men who are also taking GnRH agonists to lower testosterone; some testosterone converts into estrogen, so these medicines keep estrogen levels low

Anastrozole and exemestane also can be used to lower the risk of breast cancer in postmenopausal women who are at higher-than-average risk.

How aromatase inhibitors work

Aromatase inhibitors work by lowering estrogen levels in the body. This prevents estrogen from helping hormone receptor-positive breast cancer cells to grow.

Aromatase inhibitors are approved for use in postmenopausal women. Postmenopausal women have not had a menstrual period in 12 months or more.

If you are a postmenopausal woman:

• Your ovaries no longer produce estradiol, the main estrogen during the reproductive years.
• Your body still produces estrone, another form of estrogen. Estrone is made mainly in the fatty tissue and the adrenal glands (located above the kidneys). Aromatase, an enzyme, changes androgens into estrogens.

Aromatase inhibitors stop aromatase from changing androgens into estrogen. This:

• Reduces estrogen levels
• Helps control breast cancer growth
• Lowers the risk of recurrence in early-stage breast cancer

Anastrozole, exemestane, and letrozole work in similar ways and are considered equally effective. They have similar side effects, but individual experiences may vary.

In some cases, a doctor may recommend one kind of aromatase inhibitor over another based on other people’s experiences or your own medical history. You can work together to make decisions about which aromatase inhibitor to use.

How aromatase inhibitors are given

All three aromatase inhibitors are taken as daily pills.

How long are aromatase inhibitors taken?

Aromatase inhibitors can be taken for a certain number of years or continuously, depending on the cancer stage. In some cases, these medicines can also be paused temporarily for a pregnancy.

In early-stage breast cancer

In early-stage breast cancer, aromatase inhibitors can be taken for anywhere from 5 to 10 years after surgery. While standard treatment typically lasts about 5 years, your doctor may recommend continuing for up to 10 years if the cancer has a higher risk of recurrence.

Sometimes, doctors recommend taking tamoxifen for a few years, then switching to an aromatase inhibitor for another 2 to 5 years.

The length of treatment often depends on factors such as:

• Your age, and whether you are premenopausal or postmenopausal
• The risk of recurrence, based on the cancer’s pathology report and other test results
• Whether side effects interfere with your daily activities and quality of life
• Other health conditions you may have
• Whether a longer course of treatment is likely to benefit you

Your healthcare team may order tests on the cancer tissue to help decide how long you should take hormonal therapy (5 years versus 10). Genomic tests such as the Oncotype DX Recurrence Score test and MammaPrint analyze a group of genes to predict the risk of recurrence. This can help determine whether staying on treatment longer will benefit you. Your doctor can help you decide if these tests are right for you.

In metastatic breast cancer

In metastatic breast cancer, an aromatase inhibitor can be taken as long as it’s working to control the cancer.

• If one aromatase inhibitor causes difficult side effects, your doctor may switch you to a different one.
• If aromatase inhibitors stop working as well to treat the cancer, your care team may recommend a different hormonal therapy, such as a SERD, or another treatment.

Pausing aromatase inhibitors to have a baby

It is important to know that it is not safe to get pregnant while taking aromatase inhibitors. These drugs can harm an unborn baby. But pausing these medicines temporarily to get pregnant can be an option for some women.

If you are taking aromatase inhibitors and ovarian-suppressing medicine, and having children is important to you, let your doctor know.

A clinical trial called POSITIVE showed that stopping hormonal therapy temporarily to get pregnant did not increase the risk of recurrence.

• Follow-up results showed that extending the break to breastfeed did not increase short-term recurrence risk.
• The women paused hormonal therapy for up to 2 years to get pregnant, give birth, and breastfeed.

Still, longer-term follow-up is needed to see how long the women in the study remain recurrence-free, and how these numbers compare to women who don’t take a break from hormonal therapy.

Learn about one woman’s experience with pausing hormonal therapy to have a baby.

Side effects & things to remember

Aromatase inhibitors have side effects, but these can vary from person to person. Possible side effects can include, but aren’t limited to:

• Menopausal symptoms such as hot flashes; genitourinary syndrome of menopause, including vaginal dryness and irritation; and loss of interest in sex
• Bone and joint pain
• Bone loss that can lead to osteoporosis and increase the risk of fractures
• High blood pressure
• Higher cholesterol
• Insomnia and fatigue
• Nausea and vomiting
• Weakness
• Headache
• Loss of appetite
• Weight gain
• Mood changes
• Constipation or diarrhea
• Dry skin
• Hair thinning

It’s important to let your healthcare team know about any side effects you are experiencing. They can help find ways to manage them. Always talk with your providers about what you’re feeling. There are many very effective options for reducing side effects.

If side effects from a certain aromatase inhibitor become too difficult, your doctor might be able to change the medicine. Options include:

• Trying the same aromatase inhibitor made by a different manufacturer
• Changing to a different aromatase inhibitor
• Switching to another type of hormonal therapy

Remember that if you're having difficult side effects, you shouldn’t stop treatment on your own. Instead, talk to your healthcare team and see what they advise. It may take a few tries to find a medicine that works for you without difficult side effects.

If your doctor doesn’t take your concerns seriously, consider getting a second opinion.