Using Femara (Letrozole) to Prevent Breast Cancer Recurrence

Benefits and Side Effects of Aromatase Inhibitors for Breast Cancer

Femara tablets
What do you need to know about using Femara for postmenopausal breast cancer?. Photo © Gold Standard

What do you need to know about the benefits, indications, and side effects of Femara (letrozole) for breast cancer?

What Is Femara (Letrozole)?

Femara (letrozole) (commonly misspelled as fimara, femarra, and femera) is a drug in a category known as aromatase inhibitors. These drugs block the formation of estrogen made in areas other than the ovaries. Since estrogen can act as a fuel for the growth of breast cancer, Femara helps to lower your risk of breast cancer recurrence and improves your chance of survival.

If you are coping with side effects from this medication, make sure to read on about the benefits of Femara and ways in which the side effects of this drug can be managed.

Drug Type

Femara is an antiestrogen, or aromatase inhibitor. Other aromatase inhibitors include Aromasin (exemestane) and Arimidex (anastrozole.) Femara is not a steroid.

Hormone Therapy for Breast Cancer

Studies indicate that using hormone therapy for estrogen receptor positive breast cancer decreases the risk of recurrence and increases survival. There are two primary types of hormone therapy for people with breast cancer. 

Before menopause, the ovaries make the greatest amount of estrogen. If your ovaries are functioning, Tamoxifen is used to block the ability of estrogen to bind with cancer cells. 

After menopause, whether natural menopause, surgical menopause, or ovarian suppression medications, the major source of estrogen in the body is that produced from the breakdown of androgens in other locations of the body.

Aromatase inhibitors work to block this reaction which converts androgens to estrogens, thus blocking the formation of estrogen.

How Femara Works to Prevent Breast Cancer Recurrence

As noted, after menopause, the primary source of estrogen in the body is that which is produced in the form of androgens in fatty tissues in the body.

These androgens ("male" hormones) are converted to estrogen in a reaction catalyzed by an enzyme called aromatase. By inhibiting the action of aromatase, the production of estrogen is blocked. This results in less estrogen being available in the body to stimulate any remaining or dormant breast cancer cells (estrogen receptor positive breast cancer cells).

How important is treatment to reduce the risk of breast cancer recurrence? It seems we all know of someone who had breast cancer that was treated, but reappeared years or even decades later. We aren't certain how these cancer cells can lie dormant so long, but there are theories why later recurrences happen such as that of cancer stem cells which are more resilient than ordinary breast cancer cells. Late recurrence is more common with estrogen receptor positive breast cancers, making the search for adjuvant methods such as Femara so important.

It's now recommended that Zometa be started at the same time as Femara for those with postmenopausal breast cancer who have completed surgery and chemotherapy (see below).

What Does Research Tell Us About Femara

For women who have estrogen receptor positive breast cancer, and receive adjuvant chemotherapy, treatment with an aromatase inhibitor appears to reduce the risk of recurrence by up to 50 percent.

Studies looking at women who had received 5 years of Tamoxifen treatment, found that using Femara after this time, even starting a few years later, resulted in improved survival.

Women who become menopausal in the first 2 to 3 years on Tamoxifen therapy and were then switched to Femara for the remainder of 5 years, had a lower risk of recurrence than women who continued to use Tamoxifen alone for a 5 year period.

For women who are menopausal at the onset of hormone treatment, there are more benefits in using aromatase inhibitors initially than beginning with Tamoxifen.

It's not known exactly the ideal length of time that Femara shows a benefit, in other words, whether or not using Femara for a period beyond 5 years is of benefit (see below.) Talk to your oncologist as this area is changing with regard to current recommendations.

Who Can Take Femara

This drug is for women who have been diagnosed with estrogen receptor-positive breast cancer. A woman must have completed primary treatment and be in menopause. Pre-menopausal women can take Femara if their ovaries are chemically suppressed. Women who have had estrogen receptor negative breast cancer will not benefit from this drug.

Common Side Effects of Femara and Other Aromatase Inhibitors

As with other medications, side effects are common with Femara. The most common side effects are hot flashes and muscle and joint pain. In fact, muscle and joint pain is one of the more common reasons for which people stop taking the medication (see below).

Hot flashes are also very common, though people who switch over from tamoxifen to Femara after becoming postmenopausal (due to age, surgery, or ovarian suppression therapy) note that the hot flashes seem to be milder on Femara than on tamoxifen. Though this side effect is frustrating, anything which reduces estrogen in our bodies can lead to hot flashes, and reducing estrogen is the best way to reduce the risk of recurrence. Some people have found it helpful to "reframe" and look at hot flashes as a sign that treatment is working.

Other side effects that are fairly common include headaches, fatigue, increased perspiration, and insomnia). Learn about the dangers of insomnia for cancer patients as it may reduce breast cancer survival, but treatment options are available.

Aromatase inhibitors can also cause bone loss which can lead to osteoporosis, though the combined use of Femara with Zometa (a recommendation made in 2017) may negate this (see below).

Aromatase inhibitors do not appear to increase the risk of fatal heart attacks and strokes relative to tamoxifen use, but are associated with less serious heart problems such as abnormal heart rhythms and pericarditis (inflammation of the lining of the heart)

Muscle Aches/Side Effects and Discontinuing Treatment

Unfortunately, muscle and joint aches are a very common side effect of treatment with Femara. In one large study it was found that 32 percent of patients discontinued their use of this drug due to side effects. Nearly 24 percent of people stopped the drug due to muscle and joint aches. It's important to note that among those who stopped their aromatase inhibitor due to side effects, a third were able to tolerate one of the other medications in this class of drugs.

Talk to your doctor about what you can do to help you cope with joint and muscle aches. In one controlled trial it was found that acupuncture was more helpful than sham acupuncture in relieving muscle aches due to aromatase inhibitors.

Hot flashes can also be annoying, and are expected since the medications are decreasing the production of estrogen in your body.  Check out these thoughts on ways to cope with hot flashes.

Osteoporosis Prevention

The use of aromatase inhibitors does increase bone loss, and has been noted to not only increase the risk of osteoporosis, but the number of bone fractures among women who use these drugs. Talk to your doctor about screening for osteoporosis. Make sure that you are getting adequate vitamin D and calcium. In fact, optimal vitamin D levels in your blood or correlated with breast cancer survival, so talk to your doctor about having your vitamin D level tested, and what you can do if the level is low.

Many oncologists recommend getting a bone density test when aromatase inhibitors are started, and intermittently later on.

Combined Use of Femara and Zometa and Bone Loss

For those diagnosed with postmenopausal breast cancer, oncologists are now often beginning the bisphosphonate Zometa (zoledronic acid) at the same time. Zometa not only reduces the risk of bone loss and osteoporosis with aromatase inhbitors, but reduces the risk of recurrence as well.

Tradeoffs

The temporary side effects of Femara are much more tolerable when you know that your risk of recurrence is greatly reduced. Women who took Femara after five years of Tamoxifen had a significantly lower risk of recurrence that those who took a full five years of Tamoxifen. In addition, with Femara, your risk of a new cancer in the opposite breast is less than with Tamoxifen alone.

Dosing Recommendations

Take Femara once a day with water. This drug does not have to be taken with food. Try to take it at the same time each day, to maintain an even level of the drug in your system. If you miss a dose, don’t double up, just wait till the next day and resume your medication schedule. Do not take this drug if you are still having menstrual periods or are pregnant.

It is available as a 2.5 mg pill, brand name (no generic version available), and prescription only.

Should Femara Be Used Longer Than 5 Years?

Recommendations as to the optimal duration of Femara (and other aromatase inhibitors) are currently being debated. Earlier recommendations were for 5 years following primary treatment with surgery and possibly chemotherapy and/or radiation therapy but this may change.

When to Call Your Doctor

More serious side effects, such as heart disease, may sometimes occur. Symptoms which should prompt you to call your doctor include difficulty breathing, chest pain, leg pain or swelling, unusual vaginal bleeding, a skin rash, diarrhea, or nausea and vomiting.

Bottom Line on the Use of Femara for Postmenopausal Breast Cancer

When used following the primary treatment of breast cancer (with surgery, and chemotherapy and/or radiation therapy), Femara can reduce the risk of recurrence. It is recurrence, and metastatic disease in general that is the primary cause of deaths from breast cancer.

Femara is indicated for postmenopausal women or those who are premenopausal but have had ovarian suppression therapy. Common side effects include hot flashes and muscle aches and pain. More serious side effects such as non-fatal heart disease and osteoporosis may also occur. With the addition of bisphosphonate therapy, however, the risk of bone loss appears to be reduced.

Femara is recommended for at least 5 years following primary treatment, but recent studies are suggesting that longer use may be recommended in the future.

Sources:

Dhesy-Thind, S., Fletcher, C., Blanchette, P. et at. Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology. 2017. 35(18):2062-2081.

Hague, R., Shi, J., Schottinger, J., et al. Cardiovascular Disease After Aromatase Inhibitor Use. JAMA Oncology. 2(12):1590.

Halsey, E., Xing, M., and R. Stockley. Acupuncture for joint symptoms related to aromatase inhibitor therapy in postmenopausal women with early-stage breast cancer: a narrative review. Acupuncture in Medicine. 2015. 33:188-195.

Henry, N., Azzouz, F., Desta, A. et al. Predictors of Aromatase Inhibitor Discontinuation as a Result of Treatment-Emergent Symptoms in Early-Stage Breast Cancer. Journal of Clinical Oncology. 2012. 30(9):936-942.

Senkus, E., Kyriakides, S., Ohno, S. et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2015. 26 (suppl 5):v8-v30.

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