Femara (Letrozole) to Prevent Breast Cancer Recurrence

How the Drug Works in Postmenopausal Women

doctor talking to mature female patient
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Femara (letrozole) is a drug used to treat certain types of breast cancer in women after menopause. It works by blocking the formation of estrogen in the body. By doing so, Femara is able to prevent recurrence of hormone receptor-positive breast cancer (the type whose growth is influenced by estrogen). Femara can be used in post-menopausal women with early-stage, advanced, or metastatic breast cancer who have this hormone receptor status.

It works differently than tamoxifen (which also treats hormone-responsive breast cancer) in that it is only effective in post-menopausal women. Femara may be used with tamoxifen, but only in post-menopausal women who have been on tamoxifen for at least five years.

According to a 2018 study in BMC Cancer, recurrence and metastatic disease are among the primary causes of death from breast cancer.

How It Works

Femara belongs to a class of drug known as aromatase inhibitors. These drugs work by inhibiting an enzyme called aromatase, which facilitates the conversion of testosterone (an androgen) to estradiol (the predominant form of estrogen).

Estrogen is produced mainly in the ovaries in pre-menopausal women. In post-menopausal women, whose ovaries are no longer functional, estrogen is produced mainly in the brain, liver, breasts, bones, skin, pancreas, and adipose (fat-storing) cells. Femara is able to block the conversion of testosterone in these so-called peripheral tissues, making it effective for post-menopausal women.

Femara works only in post-menopausal women because of the way that it blocks estrogen synthesis.

By contrast, aromatase only expresses itself in parts of the ovaries called the follicles and corpus luteum. As such, Femara cannot suppress estrogen in women with functioning ovaries to a degree considered beneficial. Premenopausal women would be better served to take tamoxifen, which blocks estrogen receptors on breast cancer cells.

Other aromatase inhibitors include Aromasin (exemestane) and Arimidex (anastrozole).

Who Can Take It

The FDA approved the use of Femara in three specific groups:

  • Postmenopausal women with hormone-receptor-positive, early-stage breast cancer right after surgery (or chemotherapy and radiation)
  • Postmenopausal women with hormone-receptor-positive, early-stage breast cancer who have taken tamoxifen for five years
  • Postmenopausal women diagnosed with advanced-stage or metastatic hormone-receptor-positive breast cancer

Treatment can begin once the primary cancer treatments are completed. For women with estrogen-receptor-positive breast cancer who take an aromatase inhibitor with chemotherapy, the risk of recurrence may drop by as much as 50 percent.

Women with estrogen receptor-negative breast cancer will not benefit from Femara.

Premenopausal women may take Femara, but only if their ovaries have been chemically suppressed.

Dosage

Femara (letrozole) is available by prescription as an enteric-coated, 2.5-milligram (mg) pill.

Take Femara once daily with or without food. Try to take it at the same time every day to maintain a consistent level of drug in your system. If you miss a dose, do not double up; simply wait until the next day and resume your medication schedule as usual.

The optimal duration of Femara use is still under debate. Early guidelines had stated that Femara should be used for no longer than five years due to concerns about the drug's long-term effect on bones. However, those recommendations were based on a five-year study that was terminated early due to Femara's favorable effects.

A 2018 study in the New England Journal of Medicine reported that women taking Femara for a period of up to 10 years had an overall survival rate of 93 percent (meaning that 93 percent were still alive after 10 years).

While the incidence of bone disorders was seen to increase, the researchers concluded that the extended use of Femara in preventing cancer recurrence largely outweighed the risks.

Side Effects

As with other medications, there are side effects associated with Femara use. The most common are:

  • Headaches
  • Abnormal weakness
  • Flushing
  • Swelling of the feet or legs (edema)
  • Joint pain (arthralgia)

Of these, joint pain is one of the more common reasons why women stop taking Femara. According to the FDA, no less than 24 percent of women terminated treatment as a result of drug-induced arthralgia.

Hot flashes are also common, although they tend to milder than what might occur with tamoxifen. Though this side effect can be frustrating, it is both an indication that estrogen is being suppressed and the medication is working.

Complications

The bigger concern, perhaps, is that aromatase inhibitors like Femara can promote bone loss which, in turn, can lead to osteoporosis. On the flip side, Femara does not increase the risk of heart attack or stroke in the way that tamoxifen can, although it may cause abnormal heart rhythms (arrhythmia) and heart inflammation (pericarditis) in some.

With regards to bone loss, a study conducted in 2017 showed that the combined use of Femara with the drug Zometa (zoledronic acid) can almost entirely negate this effect. Zometa is delivered intravenously (into a vein) once yearly in a 5-milligram dose. Side effects may include fatigue, anemia, muscle aches, edema, and fever, though these tend to occur after the first infusion and reduce with subsequent infusions.

When to Call Your Doctor

Serious side effects, especially those involving the heart, should be looked at immediately. Symptoms may include heart palpitations, shortness of breath when reclining, and sharp chest pains traveling to the left shoulder and back.

Drug Interactions

Femara may interact with any drug that directly influences estrogen levels. These include hormonal contraceptives containing ethinylestradiol and Premarin (conjugated estrogens) used to treat hot flashes and other menopause symptoms. Alternative medications would need to be found if you are to take Femara.

Contraindications

Femara is contraindicated for use during pregnancy as it is known to cause fetal harm, including spontaneous abortion and congenital birth defects.

If Femara is used for any reason in pre-menopausal women, one or more non-hormonal forms of contraception should be used to prevent pregnancy, such as condoms, a diaphragm with a spermicide, or a non-hormonal IUD (like the ParaGard IUD). Even after Femara is stopped, contraception should be continued for no less than three weeks until the drug is fully out of the system.

Femara should also be avoided in anyone with a known hypersensitivity to letrozole or any of the ingredients in Femara. Although allergy and anaphylaxis are extremely rare with Femara, they have been known to occur. As such, if you've had a previous allergic reaction to Femara, you should not be rechallenged with the drug at a later date.

Other Considerations

Femara should be used with caution in women with kidney or liver disease. The dose should be decreased by 50 percent in women with cirrhosis or severe liver dysfunction. The dose may also need to be adjusted if in women with kidney failure or severe kidney impairment.

Efforts should be also made to monitor your bone density while taking Femara. Talk to your doctor about screening for osteoporosis and regularly checking your vitamin D levels as well.

Studies have shown that optimal vitamin D levels translate to improved breast cancer survival rates, so speak with your doctor about ways to increase your dietary intake and which form of supplementation is most appropriate.

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