If you’ve been diagnosed with hormone receptor-positive breast cancer, you might start treatment with hormonal therapy. Aromatase inhibitors, including letrozole (Femara) and anastrozole (Arimidex), are a common option for people who’ve gone through menopause.

Making treatment choices can feel overwhelming, especially because you’ll likely take this medication long term, but understanding your options can help. Breast cancer treatment should be a shared decision made between you and your breast cancer care team. Continue reading to learn more about letrozole and anastrozole so, working with your doctor, you can make a well-informed decision.

What Are Aromatase Inhibitors?

Letrozole and anastrozole belong to a class of medications called aromatase inhibitors. These hormonal therapies are used to treat hormone receptor (HR)-positive breast cancer. Most people take an aromatase inhibitor for five to 10 years. An aromatase inhibitor is often taken after breast cancer surgery and referred to as adjuvant treatment. If the drug is started before surgery, it’s known as neoadjuvant therapy.

Three aromatase inhibitors are approved by the U.S. Food and Drug Administration (FDA) for the treatment of breast cancer: letrozole, anastrozole, and exemestane (Aromasin).

How Do Aromatase Inhibitors Work?

Aromatase inhibitors lower estrogen levels by blocking the production of this hormone in your body. Estrogen is made by aromatase, which is an enzyme (a type of protein that speeds up chemical reactions). Aromatase is found mostly in fat cells throughout your body.

Aromatase converts the hormone androgen into estrogen. Blocking aromatase causes estrogen levels to fall by about 95 percent, according to the University of Texas MD Anderson Cancer Center. Lower estrogen can help stop or slow the growth of cancer cells that are fueled by estrogen.

Who Can Take Aromatase Inhibitors?

Aromatase inhibitors can block estrogen production in your fat cells, but they can’t stop your ovaries from making estrogen. For this reason, aromatase inhibitors are most useful after menopause, when the ovaries stop making estrogen.

People who need hormonal therapy before menopause may take another medication, such as tamoxifen (Soltamox). However, clinical trials have found that aromatase inhibitors prevent breast cancer recurrence (return of the cancer) about 30 percent more effectively than drugs such as tamoxifen. Therefore, after menopause, aromatase inhibitors are considered a first-line (preferred) hormone therapy for people with estrogen receptor-positive breast cancer.

Is Letrozole or Anastrozole More Effective?

Clinical trials have found no significant difference in effectiveness between letrozole and anastrozole.

One of the most important studies comparing these two medications was the Femara Versus Anastrozole Clinical Evaluation (FACE) trial. This study included more than 4,000 postmenopausal women with HR-positive or node-positive early-stage breast cancer. Participants were randomized into two groups, with one group taking letrozole and the other taking anastrozole for five years or until breast cancer returned.

Researchers began the FACE study with a hypothesis (guess) that letrozole might work better than anastrozole. However, the results showed that letrozole didn’t lead to significantly better outcomes. The researchers measured the study’s outcomes by determining how many participants survived at least five years without breast cancer returning — also known as disease-free survival (DFS). They also measured the overall survival rate, or the percentage of participants still alive after five years.

The five-year DFS rates were 84.9 percent for letrozole and 82.9 percent for anastrozole. Even though DFS was slightly higher for participants taking letrozole, the difference wasn’t statistically significant. The overall survival rate was also similar for both groups, with 89.9 percent for participants receiving letrozole and 89.2 percent for those getting anastrozole.

How Do You Take Letrozole and Anastrozole?

Both letrozole and anastrozole come in tablets that you swallow with water. You can take either medication with or without food, but you should take it at the same time each day.

You should always take your medication exactly as your doctor prescribes.

What Are the Side Effects?

Like all drugs, even those sold over the counter, hormonal treatment for breast cancer comes with side effects. Many side effects of letrozole and anastrozole are similar. Both medications decrease the amount of estrogen in your body, resulting in adverse events (side effects) such as:

• Hot flashes — Sudden feeling of warmth
• Night sweats — Waking up soaked in sweat
• Vaginal dryness — Decreased vaginal lubrication that can cause pain during sex
• Osteoporosis — A condition that weakens your bones
• Arthralgia — Joint pain
• Mood swings — Changes in mood or feelings of irritability

How Do the Side Effects of Letrozole and Anastrozole Differ?

The FACE study found no significant differences in the safety of letrozole and anastrozole. Both medications had about the same rate of side effects. However, not everyone reacts to medications the same way.

Differences in individuals and how each drug works may influence the likelihood of certain side effects. For example, letrozole has been shown to lower estrogen more strongly than anastrozole does. It’s possible that this may lead to more side effects in some people.

Joint Pain

Letrozole may be more likely to cause joint pain than anastrozole. In a 2020 study comparing almost 200 people taking either letrozole or anastrozole, more than half of all participants experienced joint pain. The researchers found that people on letrozole were significantly more likely to experience this side effect than those on anastrozole.

Joint pain can affect the tolerability of aromatase inhibitors, leading to stopping the medication early. People taking letrozole were more likely to cut their treatment short due to joint pain.

This study also found that a higher body mass index (BMI) was associated with joint pain while taking an aromatase inhibitor. Many people report weight gain during breast cancer treatment, which may raise the risk of aching joints.

If you experience joint pain, talk to your doctor about the best ways to treat this symptom and how to manage your weight as a breast cancer survivor.

Bone Fractures

All aromatase inhibitors can cause osteoporosis, or weakened bones. Recent research suggests that anastrozole is more strongly associated with fractures than letrozole.

A 2020 study looked at the FDA Adverse Event Reporting System (FAERS) for side effects reported by people taking aromatase inhibitors between 2004 and 2018. Researchers found that anastrozole was more closely linked to bone fractures. More research is needed to find out why anastrozole may cause more bone fractures.

Talk to your doctor about how you can prevent osteoporosis and bone fractures.

What Is the Effect on Quality of Life?

You’ll likely take letrozole or anastrozole for several years, so tolerability and its effect on your quality of life are important. The good news is that both drugs are generally well tolerated.

Even though side effects are common, they won’t necessarily reduce your overall quality of life. A 2011 study in the United Kingdom aimed to find out how the same people would tolerate letrozole versus anastrozole. Using a crossover study design, the researchers gave about 180 people each drug for 12 weeks. The findings showed that neither letrozole nor anastrozole had a negative effect on quality of life.

When asked which medication they preferred taking, about 30 percent of participants said they like letrozole better, and about 36 percent preferred anastrozole. The remainder had no preference.

What’s the Best Treatment for You?

Deciding on the best treatment for you should be a shared decision between you and your doctor. Make sure to share your treatment goals and any concerns you have. Listen to what your oncologist has to say about potential benefits and risks. If you’re worried about a particular side effect, discuss ways it may be prevented or managed if it develops. By participating fully in the decision, you’ll feel more confident about your treatment plan.

Talk With Others Who Understand

MyBCTeam is the social network for people with breast cancer and their loved ones. On MyBCTeam, more than 65,000 members come together to ask questions, give advice, and share their tips with others who understand life with breast cancer.

Is letrozole or anastrozole part of your treatment plan for hormone receptor-positive breast cancer? How has using this drug worked out for you? Share your experiences in the comments below, or start a conversation by posting on your Activities page.