Hormonal therapy for breast cancer

Hormonal therapy is a group of medicines that can treat hormone receptor-positive (HR+) breast cancer. These cancers may test positive for estrogen receptors (ER+) and/or progesterone receptors (PR+). This means estrogen and/or progesterone can signal the cancer to grow. Hormonal therapy blocks or lowers these hormones, preventing them from helping the cancer grow.

Hormonal therapy interferes with breast cancer growth in different ways, such as:

• Blocking estrogen from attaching to breast cancer cells and sending growth signals to them
• Lowering estrogen levels in the body, making estrogen less available

Your doctor may use other terms for this treatment, such as endocrine therapy or anti-estrogen therapy.

In ductal carcinoma in situ, or DCIS (non-invasive breast cancer that is confined to the milk duct) and early-stage breast cancer (cancer that has not traveled beyond the breast or underarm lymph nodes), hormonal therapy can:

• Reduce the risk of breast cancer recurrence (coming back)
• Reduce the risk of developing new breast cancers
• Improve survival

In metastatic breast cancer (cancer that has spread beyond the breast to other parts of the body), the goal of hormonal therapy is to shrink the cancer or keep it from continuing to spread.

Some hormonal therapies are only approved for use in women who are postmenopausal (stopped having periods for a year). But pre- and perimenopausal women (women who are still having periods) are still able to take them if they also take medicine that suppresses ovarian function to lower estrogen even more.

What is hormonal therapy for breast cancer?

Hormonal therapy is medicine that can be used to treat hormone receptor-positive breast cancer.

When breast cancer is hormone receptor-positive, it means that the cancer cells have tested positive for hormone receptors.

• Receptors are proteins on the cells’ surface that attach to the reproductive female hormones estrogen or progesterone, or both.
• The hormones then signal the breast cancer cells to grow.

There are different types of hormonal therapy. Some work by blocking the hormone receptors or reducing the number of receptors on cell surfaces. Others lower how much estrogen is made in the body. This can slow or stop the growth of hormone receptor-positive breast cancers.

Hormonal therapy is not used to treat hormone receptor-negative breast cancers.

Hormonal therapy is not hormone replacement therapy

It’s important to know that hormonal therapy for breast cancer is not the same as hormone replacement therapy, or HRT.

• Hormone replacement therapy is given to increase estrogen levels for women whose estrogen levels are lower due to perimenopause or menopause. This can help relieve menopausal symptoms such as hot flashes and vaginal dryness. Hormone replacement therapy is sometimes also called estrogen replacement therapy, or ERT.
• Generally, hormone replacement therapy is not recommended if you’ve had, or are at risk for, breast cancer. However, low-dose vaginally inserted estrogen may be an option for some women, because less estrogen is absorbed by the body that way. Your healthcare team is the best source of advice on hormone replacement therapy and managing side effects.
• For transgender people at high risk for or diagnosed with breast cancer, gender-affirming hormone therapy that contains estrogen can increase risk of breast cancer development or growth. Visit Breast cancer and transgender people to learn more.

Who gets hormonal therapy for breast cancer?

Hormonal therapy is recommended for people with hormone receptor-positive breast cancer. This means the cancer tests positive for estrogen and/or progesterone receptors.

• These receptors can attach to the hormones estrogen, progesterone, or both.
• About two in every three female breast cancers are hormone receptor-positive.
• In men, about 80-90% of breast cancers are hormone receptor-positive. Men’s bodies produce small amounts of these hormones.

Confirming hormone receptor status

After a biopsy to check for breast cancer, your doctor will have a tissue sample tested for estrogen and progesterone receptors. This is called immunohistochemistry testing. You and your doctor will review the test results in your pathology report.

The cancer is considered hormone receptor-positive (HR+) if it tests positive for:

• Estrogen receptors and progesterone receptors (you may see this written as ER+/PR+)
• Estrogen receptors, but not progesterone receptors, or ER+/PR-
• Progesterone receptors, but not estrogen receptors, or ER-/PR+

For a positive finding, the results should also tell you what the degree of positivity is. This is often reported as either a percentage or a number on a scale. The higher that percentage or number is, the more hormone receptors the breast cancer has.

• Most hormone receptor-positive breast cancers test positive for both estrogen receptors and progesterone receptors (ER+/PR+).
• Some test positive only for estrogen receptors (ER+/PR-).
• It is less common for breast cancers to be estrogen receptor-negative and progesterone receptor-positive (ER-/PR+).

How does hormonal therapy work?

Different types of hormonal therapy work in different ways. Depending on what type of medicine you receive, hormonal therapy can:

• Block estrogen from attaching to hormone receptors on breast cancer cells
• Stop the body from making as much estrogen so that there is less circulating in the body
• Break down and reduce the number of estrogen receptors so that estrogen can’t attach to cancer cells and fuel their growth
• Temporarily stop the ovaries from working, which lowers estrogen levels; this approach can be used for people who are pre- and perimenopausal (still having monthly periods)

Menopausal status and hormonal therapy

For women, menopausal status can help determine which hormonal therapies are recommended. Some hormonal therapies are FDA-approved for all women by the U.S. Food & Drug Administration (FDA). Others are only FDA-approved for use in postmenopausal women.

Understanding your menopausal status

Menopausal status is defined in three ways:

• Premenopausal: You are still having monthly periods and you’re able to get pregnant (unless you have a condition that affects fertility). Your ovaries are still working, and they make most of the body’s estrogen and progesterone.
• Perimenopausal: You still have periods, but not every month. Your flow may be much lighter or heavier than usual. Hormone levels tend to swing up and down. Perimenopause usually lasts 3 to 4 years, but its length can vary from a few months to about 10 years. Pregnancy is still possible during perimenopause.
• Postmenopausal: You’ve gone a full year (12 months in a row) without a period. Your ovaries no longer release eggs, and you can no longer get pregnant. Estrogen and progesterone levels fall. Other tissues in the body still produce these hormones, but in smaller amounts.

When choosing hormonal therapy, perimenopausal women are usually considered to be premenopausal. Testing hormone levels to see how “close” you are to menopause isn’t always helpful. During perimenopause, estrogen and progesterone levels can swing from very high to very low. Your doctor can discuss options with you, based on your medical history.

Hormonal therapy options and menopausal status

One hormonal therapy, tamoxifen, a selective estrogen modulator (SERM), is approved for use in women of any menopausal status.

Some hormonal therapies are only approved for use in postmenopausal women:

Aromatase inhibitors

Aromatase inhibitors (anastrozole, exemestane, letrozole) lower the amount of estrogen in the body.

• These drugs block an enzyme in fat tissue called aromatase. This enzyme is a protein that can change the hormone androgen into estrone, a form of estrogen.
• In postmenopausal women, fatty tissue is the body’s main source of estrogen. By lowering estrogen, aromatase inhibitors can slow or stop the growth of hormone receptor-positive cancer cells.

Selective estrogen response degraders

Selective estrogen response degraders, or SERDs (fulvestrant, elacestrant), block estrogen from signaling breast cancer cells to grow.

• SERDs work by attaching to estrogen receptors and breaking them down. With fewer receptors, the cancer cells can’t get the estrogen they need to grow.
• The SERDs fulvestrant and elacestrant were proven to be effective in studies involving postmenopausal women. The SERDs were given after the cancer stopped responding to another type of hormonal therapy—usually an aromatase inhibitor.
• SERDs are being studied in premenopausal women.

Pre- and perimenopausal women can often take aromatase inhibitors or fulvestrant if they use ovarian suppression medicines at the same time, or if they have had their ovaries removed.

Ovarian suppression for premenopausal women

Ovarian suppression means using medicine or surgery to stop the ovaries from making estrogen.

Pre- and perimenopausal women can usually take aromatase inhibitors or the SERD fulvestrant if they also use ovarian suppression to reduce estrogen to postmenopausal levels.

Ovarian suppression options include:

• Taking a GnRH agonist to temporarily stops the ovaries from working
• Having the ovaries removed (oophorectomy), which leads to permanent menopause

Research on ovarian suppression and risk of recurrence

Tamoxifen, a hormonal therapy approved for use in women of any menopausal status, is often the first choice for premenopausal women. But two clinical trials (called SOFT and TEXT) found that taking an aromatase inhibitor along with ovarian suppression medicines is better at reducing the risk of recurrence in early-stage, hormone receptor-positive breast cancer that has a high risk of recurrence. In premenopausal women with high-risk breast cancer, it was more effective than tamoxifen alone and tamoxifen plus ovarian suppression medicine.

Still, it's important to know that the SOFT and TEXT trials did not show that all premenopausal women with hormone receptor-positive early-stage breast cancer benefit from ovarian suppression. Women with a lower risk of recurrence did as well with tamoxifen alone.

Deciding whether ovarian suppression is right for you

If you are premenopausal and considering hormonal therapy, talk with your doctor about whether it would be helpful to add ovarian suppression to your treatment.

Ovarian suppression causes more intense menopausal symptoms than hormonal therapy alone. However, your doctor may recommend ovarian suppression based on your situation and risk of recurrence. This can depend on:

• Your age
• The features of the cancer
• Whether any lymph nodes contained cancer

How is hormonal therapy given?

Most types of hormonal therapy are taken as a daily pill.

There are also some hormonal therapies available as:

• A liquid, taken by mouth
• An injection into a muscle
• A tiny implant that is injected under the skin

It's important to take hormonal therapy on time according to your care team’s recommendations. If you have difficult side effects or are thinking about stopping hormonal therapy for any reason, talk to your healthcare team. They can help with managing side effects. They can also recommend a different hormonal therapy that is easier to tolerate.

You should not take hormonal therapy if you’re pregnant or planning to become pregnant. Hormonal therapy is not safe for an unborn baby. However, research shows that it is safe to pause hormonal therapy temporarily to get pregnant and carry a baby to term.

When is hormonal therapy given?

In early-stage breast cancer, hormonal therapy is usually given after surgery. This is also called adjuvant therapy.

If the cancer is too large to be removed with lumpectomy, or if surgery is delayed, your doctor may recommend starting hormonal therapy before surgery. This is called neoadjuvant therapy.

If you would prefer not to have a mastectomy, neoadjuvant hormonal therapy may increase the chances you can have a lumpectomy instead. Generally, hormonal therapy would be taken for about 4 to 8 months before surgery and continued after surgery. Exact schedules can vary.

For metastatic breast cancer, hormonal therapy can be given continuously, for as long as it slows or stops the cancer’s growth.

People usually start taking hormonal therapy after surgery, chemotherapy, and radiation therapy are complete. However, hormonal therapy may also be given at the same time as other treatments, including:

• Chemotherapy
• Radiation therapy
• Targeted therapies for hormone receptor-positive breast cancer, including:
  • Abemaciclib (Verzenio)
  • Alpelisib (Piqray)
  • Capivasertib (Truqap)
  • Everolimus (Afinitor)
  • Inavolisib (Itovebi)
  • Palbociclib (Ibrance)
  • Ribociclib (Kisquali)

How long will I take hormonal therapy?

In metastatic breast cancer, hormonal therapy can be given on an ongoing basis.

In early-stage breast cancer, hormonal therapy usually lasts anywhere from 5 to 10 years after surgery. Some people take the same medicine the entire time. Others might start on one medicine for a few years and then switch to another.

Your healthcare team will help you figure out the right schedule for you. The length of hormonal therapy often depends on:

• Your age, and whether you are premenopausal or postmenopausal
• The cancer’s risk of recurrence, based on your pathology report and other test results
• How well you tolerate hormonal therapy

Your healthcare team may order tests on the cancer tissue to help decide how long you should take hormonal therapy (5 years versus 10). These tests analyze a group of genes to predict the risk of recurrence and whether a longer course of treatment makes sense. Examples include genomic tests such as EndoPredict and the Breast Cancer Index test. Your doctor can help you decide if these tests make sense for you.

As research continues, the length of hormonal therapy treatment could change. If you want to try a different treatment schedule, ask your doctor about clinical trials studying hormonal therapy schedules.

Hormonal therapy side effects

Hormonal therapies have certain side effects in common. Each person experiences them differently. Some people have intense side effects, while others find them manageable. Side effects also can vary, depending on the specific medicine you take.

Hormonal therapy side effects can include:

• Menopausal symptoms, such as hot flashes, night sweats, and vaginal dryness or irritation
• Mood swings or depression
• Fatigue
• Bone thinning or bone and joint pain
• Hair thinning
• Nausea
• Loss of interest in sex

For men, the side effects of hormonal therapy can include:

• Headaches
• Nausea and vomiting
• Skin rash
• Impotence (unable to have an erection)
• Loss of interest in sex
• Bone thinning

It’s important to stay on hormonal therapy for the recommended length of time to reduce the risk of recurrence in early-stage breast cancer. If you have difficult side effects, talk to your healthcare team. There are medicines, lifestyle changes, and other strategies that can help.

If serious side effects persist, your doctor can recommend a different hormonal therapy. Ask your care team about options.