• Hormonal therapy is useful for certain types of breast cancer.
• Hormonal therapy is not the same as hormone replacement therapy (HRT), which is prescribed for menopause symptoms.
• Various medications, each with its own side effects, may be used for hormonal therapy.

Many people who have breast cancer use hormonal therapy as a part of their treatment plan. There are several types of hormonal therapies, which are useful for controlling breast cancer cells that contain certain proteins that enable hormones to affect the cell. However, hormonal therapies won’t help if a person’s breast cancer cells lack these proteins.

Hormones and Breast Cancer

Hormones are substances that travel throughout the body within the blood. Their job is to send signals between different parts of the body. Hormones help control body processes such as metabolism, growth, and mood. Certain hormones regulate sexual development and the reproductive system.

Most women produce high levels of the hormones estrogen and progesterone, according to the National Cancer Institute. Before menopause, the ovaries are the main source of these hormones. During menopause, the ovaries shut down and stop producing estrogen and progesterone. Other tissues, including ovaries, skin, and fat, continue to make these hormones at lower levels.

Hormone Receptors

Normal breast cells contain proteins called hormone receptors on their outer surface. There are two main hormone receptors found on these cells — estrogen receptor (ER) and progesterone receptor (PR). Hormone receptor proteins allow a cell to recognize and respond to signals from the estrogen and progesterone hormones.

When breast cells turn cancerous, they often keep their hormone receptors. In some cases, breast cancer cells lose the ability to make ER and PR. When diagnosing someone with breast cancer, doctors often perform tests to determine whether hormone receptors are present. Doctors may use several terms to describe hormone receptor status:

• Hormone receptor-positive — Breast cancer cells contain ER, PR, or both.
• Hormone receptor-negative — Cells within a breast tumor do not have ER or PR.
• ER-positive — Cells contain ER.
• PR-positive — Cells contain PR.
• Triple-positive — Breast cancer cells contain ER and PR and also make too much of a protein called human epidermal growth factor receptor 2 (HER2).
• Triple-negative — Cells don’t contain either hormone receptor and don’t make HER2.

Knowing whether breast cancer cells contain ER, PR, or HER2 helps doctors understand what type of breast cancer you have, predict its course, and plan treatments.

How Does Hormonal Therapy Work?

Hormone receptor-positive breast cancer cells still rely on hormones to grow and survive, even though they have changed and mutated. Hormonal therapy blocks natural hormones in the body and disrupts this process. Some types of hormonal therapy attach to hormone receptors on the cell surface, preventing them from interacting with the body’s hormones. Other hormonal therapy drugs cause the body to make less estrogen and progesterone. Either way, hormonal therapy prevents ER-positive or PR-positive breast cancer cells from receiving signals from the body’s hormones.

Hormonal therapy has several purposes. These drugs can prevent cancer cells from growing and dividing. The medications travel throughout the bloodstream, reaching cancer cells that have spread to other places, and can also help prevent relapse (having the cancer come back after it is treated).

Hormonal Therapy Differs From Hormone Replacement Therapy

Hormonal therapy drugs for treat breast cancer are different from hormone replacement therapy. HRT, which is sometimes used to reduce symptoms of menopause, involves taking drugs that contain estrogen or progesterone. HRT is the opposite of breast cancer hormonal therapy, which aims to reduce or block hormones. People may have to quit HRT treatments if they are diagnosed with breast cancer.

When Is Hormonal Therapy Used?

About 2 out of 3 people with breast cancer have hormone receptor-positive cancer cells, according to the American Cancer Society. For this group, hormonal therapy may be an option at different points along the treatment journey:

• Hormonal therapy can help shrink breast tumors before they are surgically removed. This is called neoadjuvant therapy.
• These medications may be taken for five to 10 years after surgery to prevent the cancer from relapsing (returning). This is called adjuvant therapy.
• Hormone therapies can treat metastatic breast cancer (cancer that has spread to distant places in the body).
• The U.S. Food and Drug Administration (FDA) has approved hormonal therapy as a risk-reduction strategy. Individuals in specific situations who have a high likelihood of developing breast cancer can take these medications to reduce risk.

People who have hormone receptor-negative breast cancer don’t undergo hormonal therapy. These medications don’t work unless the cancer cells contain ER or PR.

Types of Hormonal Therapy

There are several hormonal therapy options, which work in different ways to fight cancer. Doctors may recommend different hormonal therapies based on the breast cancer stage (how far cancer has spread within the body) and whether a person has gone through menopause. Overall health, bone density, and risk of developing certain diseases also factor into the decision.

Tamoxifen

Tamoxifen is a type of hormonal therapy called a selective estrogen receptor modulator (SERM). Tamoxifen binds to ER proteins and prevents estrogen from reaching the cell. A once-a-day pill, tamoxifen is usually taken for five years after surgery. This medication is more commonly prescribed to those who are premenopausal (haven’t yet gone through menopause) and are still producing high levels of estrogen. However, it may also be a good option for those who are postmenopausal (have not had a period in at least one year).

Two other drugs are approved by the FDA to treat those who are postmenopausal. Fareston (a formulation of toremifene) works in a similar way as tamoxifen. Faslodex (fulvestrant) also attaches to hormone receptors, but instead of simply getting in the way of estrogen, it damages and destroys the ER protein, rendering cancer cells unable to use the body’s estrogen.

Aromatase Inhibitors

Aromatase inhibitors are drugs that reduce estrogen levels within the body. This treatment prevents an enzyme called aromatase from converting prehormones into estrogen within the ovaries, fat, and other tissues.

According to the National Cancer Institute, most women who use aromatase inhibitors have already gone through menopause and are not currently producing high levels of estrogen. Those who are premenopausal and take these drugs end up diverting pre-estrogens into male hormones, leading to possibly undesired effects. Taking aromatase inhibitors along with other treatments may prevent the ovaries from making these prehormones.

Aromatase inhibitors include anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin). All these drugs are pills taken once a day. Some people take aromatase inhibitors daily for five years. Others may take aromatase inhibitors for two or three years, then switch to tamoxifen for two or three years or vice versa. Based on recent studies, 10 years of aromatase inhibitors is now recommended as preventive therapy after breast surgery.

Treatments To Shut Down the Ovaries

Surgery or medication can prevent the ovaries from making estrogen. These treatments, often called ovarian ablation or ovarian suppression, trigger menopause in those who are premenopausal. They are often used along with treatments like aromatase inhibitors.

Potential breast cancer treatments that help shut down the ovaries include:

• Oophorectomy (surgery to remove the ovaries)
• Radiation therapy to damage the ovaries
• Luteinizing hormone-releasing hormone agonist drugs, including leuprolide (Lupron) and goserelin (Zoladex), to temporarily stop estrogen production
• Chemotherapy to damage the ovaries

Side Effects of Hormonal Therapy

Research has shown that hormone therapies can kill cancer cells and help prevent the risk of breast cancer relapses. However, these drugs also come with potentially serious side effects. You will have to talk to your doctor to figure out whether the benefits of this treatment outweigh the risks.

According to the American Cancer Society, for premenopausal women, any hormonal therapies that reduce the effects of estrogen will lead to menopause symptoms. This is also true for treatments that shut down the ovaries. The side effects of hormone therapy — hot flashes, chills, night sweats, vaginal dryness, insomnia, and mood swings — usually improve with time, as with regular menopause, but some medications can help.

Tamoxifen Side Effects

Tamoxifen and similar drugs may lead to weight gain, nausea, skin rashes, swelling, headaches, and tiredness.

MyBCTeam members have reported a wide range of experiences when taking tamoxifen. “I had no effects on tamoxifen except mild hot flashes — but I was getting them at the end of chemo anyway,” reported one member. Another also reported mild side effects: “Tamoxifen caused my hair to thin some, but I started taking biotin and it’s all better.”

Other members have struggled more while taking this drug. “I had a horrible reaction so I came off,” wrote one member of MyBCTeam.

Tamoxifen and other SERMs may also lead to long-term health problems, although these are rarer. People who take tamoxifen have a higher risk of blood clots, cataracts, and stroke. They are also more likely to develop endometrial cancer (cancer of the uterus). However, this complication is rare and almost always diagnosed in the early, curable stage, when vaginal bleeding is noted.

Aromatase Inhibitor Side Effects

One of the most common side effects of aromatase inhibitors is pain in muscles or joints.

Many MyBCTeam members have reported pain while taking these drugs. Sometimes, this pain is severe. One member who had been on exemestane for several months commented, “I was in timeout due to severe pain in my knees and ankles. I could barely walk,” adding that the pain “went away within days of stopping” the treatment.

Another MyBCTeam member wrote, “I feel it has aged me, blocking all the estrogen. I am living with it — joints, bone loss, wrinkles, etc.”

Some members have found ways around this pain. One member, who was taking anastrozole, gave advice to another who was considering trying aromatase inhibitors. “I use Tylenol Arthritis as infrequently as possible and sometimes just cut the dose. Try gentle stretching before bedtime and a warm Epsom salt bath. I got my first massage since COVID, and that helped for a couple of days. My therapist gave me CBD (cannabidiol) oil to try, but I have not used it yet. The best thing for me is to walk the pain out. The more I move, the better it feels.”

Aromatase inhibitors can also cause bone loss, heart problems, and mood changes. People who use aromatase inhibitors are monitored for osteoporosis and may also need to take medications to help strengthen the bones.

Overall, aromatase inhibitors tend to lead to similar side effects. However, these effects may vary slightly from person to person, and some find that they have fewer side effects with one brand versus another. If you are having trouble with one drug, ask your oncologist if there is a possibility you can try a different 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 58,000 members come together to ask questions, give advice, and share their stories with others who understand life with breast cancer.

Have you tried hormonal therapy to treat breast cancer? Share your experiences in the comments below, or start a conversation by posting on MyBCTeam.