Exemestane (Aromasin)

How Exemestane Works

After menopause, most estrogen is made outside the ovaries, in fat and other tissues, by the aromatase enzyme. Hormone receptor-positive breast cancer cells use this estrogen to grow.

Exemestane looks like the natural hormone that aromatase normally works on. The enzyme takes it up, and exemestane then binds to it permanently, switching it off. This is why it is sometimes called an aromatase inactivator or "suicide inhibitor." The body has to make new enzyme to recover. At 25 mg a day, exemestane lowers circulating estrogen in postmenopausal women by about 85% to 95%.

Steroidal vs. nonsteroidal

• Exemestane is steroidal and binds permanently.
• Letrozole and anastrozole are nonsteroidal and bind reversibly.

Because they bind differently, cancer that has stopped responding to a nonsteroidal aromatase inhibitor may still respond to exemestane, especially with added targeted therapy. Exemestane also has a weak androgen-like effect from one of its breakdown products. Researchers hoped this would protect bone, but large trials have not shown a clear difference in fractures compared with other aromatase inhibitors.

Exemestane does not work by itself before menopause, because the ovaries make too much estrogen. It is used in premenopausal women only together with ovarian suppression.

FDA-Approved and Guideline Uses

FDA-approved

• Early breast cancer after tamoxifen: Postmenopausal women with estrogen receptor-positive early breast cancer who have taken tamoxifen for 2 to 3 years, switching to exemestane to complete a total of 5 years of hormone therapy. This is based on the Intergroup Exemestane Study (IES), where switching lowered recurrence compared with continuing tamoxifen.
• Advanced breast cancer after tamoxifen: Postmenopausal women whose cancer has grown after tamoxifen.

Common guideline-supported uses

• Upfront treatment of early breast cancer: The MA.27 trial found exemestane and anastrozole worked about equally well as first hormone therapy after surgery. Guidelines treat all three aromatase inhibitors as reasonable choices.
• With ovarian suppression before menopause: In the SOFT and TEXT trials, exemestane plus ovarian suppression lowered recurrence more than tamoxifen plus ovarian suppression in premenopausal women, with the biggest benefit in higher-risk cancers.
• With everolimus for advanced cancer: The BOLERO-2 trial led to FDA approval of everolimus (Afinitor) combined with exemestane for postmenopausal women with HR-positive, HER2-negative advanced breast cancer after a nonsteroidal aromatase inhibitor.
• Breast cancer risk reduction: In the MAP.3 trial, exemestane lowered invasive breast cancer by about 65% in high-risk postmenopausal women. ASCO lists it as an option, though it is not FDA-approved for this use.
• After intolerance of another aromatase inhibitor: Some people with joint pain on letrozole or anastrozole tolerate exemestane better, and the reverse can also be true.

Dosing and How to Take It

• Dose: 25 mg once a day.
• Take it after a meal. Food increases absorption, so the label recommends taking it after eating. Pick a regular meal, such as breakfast or dinner.
• With strong CYP3A4 inducers (for example rifampin or phenytoin): the label recommends 50 mg once daily after a meal.
• Kidney or liver problems: Drug levels rise, but no dose change is recommended in the label.
• Older adults: No dose change based on age.
• Missed dose: Take it later that day after food if you remember. If it is almost time for the next dose, skip it. Do not double up.
• Length: For early cancer, usually to complete 5 years of total hormone therapy, sometimes longer. For advanced cancer, as long as it is working.

Side Effects

Exemestane's side effects mostly come from low estrogen and are similar to those of other aromatase inhibitors.

Common side effects

• Hot flashes and sweating
• Joint pain and stiffness, sometimes muscle aches
• Fatigue
• Headache
• Trouble sleeping
• Nausea, mild stomach upset
• High blood pressure
• Low mood or depression
• Vaginal dryness and lower sex drive
• Hair thinning

In the IES trial, compared with continuing tamoxifen, women on exemestane had more joint pain and diarrhea, and fewer blood clots and gynecological symptoms such as vaginal bleeding.

Less common but important

• Osteoporosis and fractures
• Carpal tunnel syndrome and trigger finger
• Raised liver enzymes or bilirubin; rarely, hepatitis
• Lower lymphocyte counts (a type of white blood cell), usually without symptoms
• Heart problems such as heart attack or heart failure have been reported; a direct link is uncertain
• Allergic reactions or skin rash

What helps with joint pain

Regular exercise, acetaminophen or anti-inflammatory pain relievers when safe, duloxetine, and acupuncture all have evidence in women taking aromatase inhibitors. If pain persists, a short break and a switch to another hormone therapy is often possible. See the joint pain section of our anastrozole guide for details.

Bones, Vitamin D and Heart Health

Bones

• Get a baseline DEXA scan and repeat about every 1 to 2 years, or as advised.
• The FDA label recommends checking 25-hydroxy vitamin D before starting and treating deficiency.
• Get enough calcium and vitamin D, and do weight-bearing and strength exercise.
• If you have osteoporosis or high fracture risk, your doctor may recommend a bisphosphonate or denosumab. Some postmenopausal women with early breast cancer are offered a bisphosphonate to lower the risk of cancer spreading to bone.

Heart and cholesterol

Exemestane may have a smaller effect on cholesterol than nonsteroidal aromatase inhibitors in some studies, but results are mixed. Keep up with blood pressure, cholesterol and blood sugar checks with your primary care doctor, and stay active.

Drug Interactions

• Strong CYP3A4 inducers lower exemestane levels. Examples: rifampin, phenytoin, carbamazepine, phenobarbital, and the herbal product St. John's wort. If one is needed, the label recommends doubling exemestane to 50 mg daily.
• Estrogen-containing products (hormone replacement therapy, birth control pills) counteract exemestane and should not be used. Ask your oncologist before any vaginal estrogen.
• Everolimus: Commonly combined with exemestane in advanced cancer. Everolimus has its own side effects, including mouth sores, so follow its specific instructions (see our mouth sores guide).
• Supplements: Avoid concentrated soy isoflavones, red clover and other "menopause support" products unless your team approves them.
• Strong CYP3A4 inhibitors (such as ketoconazole) did not meaningfully change exemestane levels in studies.

Monitoring

• Vitamin D before starting
• Bone density at baseline and periodically
• Menopause status (estradiol and FSH) if periods stopped with chemotherapy or you are on ovarian suppression
• Blood pressure and cholesterol at routine visits
• Liver tests if symptoms suggest a problem
• Symptoms: joint pain, mood, sleep, sexual health, and whether you are able to take every dose
• Cancer follow-up: mammograms and visits as planned

Exemestane vs. Other Aromatase Inhibitors

Compared with tamoxifen, all aromatase inhibitors lower recurrence somewhat more after menopause, with fewer blood clots and uterine problems but more bone loss and joint pain. For advanced cancer, other options include fulvestrant and CDK4/6 inhibitors such as palbociclib.

Cost and Financial Help

• Generic exemestane is widely available and usually low-cost with insurance or discount cards, though often a little more expensive than generic anastrozole or letrozole. Prices vary.
• Brand Aromasin costs much more without added medical benefit.
• When combined with everolimus, the everolimus is the expensive part; ask about manufacturer assistance and copay foundations.
• Your oncology social worker or pharmacist can help with assistance programs and lower-cost pharmacies.

Frequently Asked Questions