Aromasin (Exemestane) to Prevent Breast Cancer Recurrence

Used in postmenopausal women with estrogen-dependent cancer

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woman getting a bone density scan
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Aromasin (exemestane) is a medication used to treat estrogen receptor-positive breast cancer, a type of cancer whose growth is influenced by estrogen. Aromasin belongs to a class of drugs called aromatase inhibitors that blocks an enzyme called aromatase, which the body uses to produce estrogen. By lowering levels of the hormone, a tumor is less able to grow.

Aromasin was approved for use by the U.S. Food and Drug Administration (FDA) in 1999 to prevent cancer recurrence in postmenopausal women. It is also used to treat advanced breast cancer that has progressed despite treatment with tamoxifen. It is not used in premenopausal women or in women with estrogen receptor-negative breast cancer.

Despite its benefits in preventing recurrence and extending survival, Aromasin does carry certain risks, including the potential for bone mineral loss and fetal harm.

How It Works

There are certain types of cancers whose cells have receptors for estrogen. These receptors, found inside the cell, are activated when the hormone binds to them. Breast cancers that have estrogen receptors are referred to as estrogen receptor-positive, while those without are classified as estrogen receptor-negative. Some ovarian and endometrial cancers are also influenced by estrogen.

Aromasin, like other aromatase inhibitors, slows the production of estrogen by binding to and blocking the action of aromatase. This key enzyme converts androgens (male hormones) to estrogen in both premenopausal and postmenopausal women.

Aromasin is bioactive in postmenopausal women specifically because their principal source estrogen is this conversion, as their ovaries are no longer functioning. The process mainly takes place in peripheral tissues of the breasts, liver, skin, bones, pancreas, and brain.

When taken as directed, Aromasin can suppress the production of estrogen in postmenopausal women by 85 percent to 95 percent.

The opposite is the case for premenopausal women, as the ovaries, rather than the conversion of androgens, are the main source of estrogen. Because of this, Aromasin is ineffective in these women.

Who Can Use It

Aside from being postmenopausal, women are candidates for Aromasin therapy if they have estrogen receptor-positive breast cancer. To identify a woman's hormone receptor status, a tissue sample needs to be obtained either by biopsy or during surgery.

The test would identify the number of receptors for estrogen and/or progesterone in breast cancer cells. In around two-thirds of cases, a tumor has receptors of one or both of these hormones.

There are currently two indications for Aromasin use:

  • Aromasin can be included as part of adjuvant therapy, a form of treatment used to prevent cancer recurrence after primary cancer treatment. It is prescribed as second-line therapy after tamoxifen, the primary drug used in adjuvant therapy.
  • Aromasin can also be used if an advanced breast cancer progresses after tamoxifen is used. In this case, Aromasin would be substituted for tamoxifen. They would not be taken together.

Dosage

Aromasin is supplied in a 25-milligram (mg) pill. It is taken as a once-daily, 25-mg dose immediately following a meal. Aromasin needs fat to be absorbed and is less able to do so on an empty stomach.

Side Effects

Like all medications, Aromasin can cause side effects. Many of these are associated with the steep reductions in estrogen in women already affected by hormonal decreases.

Not only may the drug induce menopausal symptoms, but it can also increase the risk of osteoporosis (porous bones due to bone mineral loss) with ongoing use.

The most common side effects of Aromasin use (in order of frequency) are:

  • Hot flashes
  • Joint pain
  • Increased sweating
  • Hair loss or thinning
  • High blood pressure
  • Insomnia
  • Nausea
  • Fatigue
  • Stomach ache
  • Depression
  • Diarrhea
  • Dizziness
  • Skin dryness, itchiness, and inflammation
  • Headache
  • Muscle ache
  • Edema (tissue swelling)
  • Anxiety

The severity of side effects can vary. Some are low-grade and resolve on their own over time. Others may persist and require ongoing management or a change in treatment. With that being said, less than 3 percent of users terminate treatment due to side effects. Allergy is considered rare with Aromasin.

Aromasin and tamoxifen have similar rates of side effects. While insomnia and joint pain are more common with Aromasin, the drug has a far lower risk of blood clots or uterine cancer compared to tamoxifen.

Bone Density Loss

In addition to the short-term side effects, Aromasin can increase the risk of osteoporosis even with adequate calcium and vitamin D intake. This poses a serious concern for postmenopausal women with cancer given that chemotherapy can also decrease bone mineral production. Even without cancer, women over 50 are five times more likely to develop osteoporosis than men.

Aromasin-induced osteoporosis can lead to the collapse of the spinal column, a loss of height, stooped posture, and an increased risk of bone fractures. The risk appears even greater than with tamoxifen.

A 2018 review of studies from Canada reported that aromatase inhibitors like Aromasin increase the risk of fractures by 33 percent compared to tamoxifen, although the risk was entirely reversed once the treatment was stopped.

Some of these risks can be mitigated with weight-bearing exercises, which promote bone mineral production. In addition to an increased intake of calcium and vitamin D, twice-yearly injections of Prolia (denosumab) or once-yearly intravenous infusions of Zometa (zoledronate) can reduce the risk of osteoporosis while aiding in the prevention of early-stage cancer recurrence.

Interactions

Aromasin is metabolized in the liver using an enzyme called cytochrome P450 3A4 (CYP 3A4). Other drugs use this same enzyme for the same purpose. If Aromasin is used alongside these drugs, it may alter the concentration of one or both drugs in the bloodstream. Decreased concentrations are associated with a loss of pharmaceutical effect, while increased concentrations can lead to drug toxicity and a worsening of side effects.

Among the drugs that can interact with Aromasin are:

  • Anti-arrhythmia drugs like quinidine
  • Anticonvulsants like Tegretol (carbamazepine) and Trileptal (oxcarbazepine)
  • Antifungal drugs like Nizoral (ketoconazole) and Vfend (voriconazole)
  • Anti-hypertensive medications like amlodipine and nifedipine
  • Antipsychotic drugs like Orap (pimozide)
  • Atypical antidepressants like nefazodone
  • HIV drugs like Reyataz (atazanavir) and Crixivan (indinavir)
  • Immune-suppressive drugs like Sandimmune (cyclosporine)
  • Macrolide antibiotics like clarithromycin and telithromycin
  • Migraine medications like Ergomar (ergotamine)
  • Opioid analgesics like Duragesic (fentanyl) and alfentanil
  • Rifampin-based drugs used to treat tuberculosis
  • Triazolo-benzodiazepine tranquilizers like Klonopin (clonazepam) and Halcion (triazolam)

In many cases, a dose adjustment of one or the other agent can compensate for the interaction. In others, a drug substitution may be needed.

St. John's Wort and grapefruit juice can also interact with Aromasin.

Before starting Aromasin, advise your oncologist about any and all drugs and supplements you may be taking, whether they are pharmaceutical, recreational, over-the-counter, or complementary/alternative.

Contraindications

Aromasin is contraindicated for use in people with a known allergy to Aromasin or any of its ingredients. In the unlikely event and allergy does occur, the treatment should be stopped, and the user should not be rechallenged with the drug a second time.

Aromasin is also currently contraindicated in premenopausal women, especially those who are pregnant or likely to become pregnant.

This is due in large part to Aromasin's classification as a Pregnancy Category X drug, meaning that there is positive evidence that the drug can cause fetal harm. The evidence to date has been limited to rat and rabbit studies in which Aromasin was shown to increase the risk of miscarriage and low birth weight.

Although aromatase inhibitors like Femara (letrozole) can be used in premenopausal women whose ovaries are chemically suppressed, the same does not currently hold true with Aromasin. But that may soon change.

According to a 2014 study in the New England Journal of Medicine, the combined use of Aromasin and tamoxifen in premenopausal women with early-stage breast cancer decreased the risk of cancer recurrence by 98.8 percent after five years compared to 88.8 percent with tamoxifen alone.

The 4,690 women who participated in the trial had their ovarian estrogen production suppressed either with medications, radiation, or oophorectomy (ovary removal). The overall rate of adverse events in both groups, including death, was statistically equal.

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