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Some breast cancers have receptors (proteins) that cause them to grow in response to hormones like estrogen or progesterone. These are usually thought of as female hormones, but men have them too, just at lower levels. In fact, most breast cancers in men are hormone receptor (HR)-positive, meaning they are estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, or both.

Treatments that stop these hormones from affecting breast cancer cells are called hormone therapy or endocrine therapy.

When is hormone therapy used for breast cancer in men?

Hormone therapy can only be used to treat hormone receptor-positive breast cancer (ER-positive, PR-positive, or both). It does not help for cancers that are hormone receptor-negative (both ER- and PR-negative).

In men with hormone receptor-positive breast cancer, hormone therapy is often used after surgery (as adjuvant therapy) to help reduce the risk of the cancer coming back. Sometimes it is started before surgery (as neoadjuvant therapy).

Hormone therapy is usually taken for at least 5 years. Treatment longer than 5 years might be offered to men whose cancers have a higher chance of coming back. A test called the Breast Cancer Index (BCI) might be done on the cancer cells to help decide if a person will benefit from more than 5 years of hormone therapy. While this test was developed based on breast cancer in women, some doctors might use it for breast cancer in men as well.

Hormone therapy can also be used to treat cancer that has come back after treatment or that has spread to other parts of the body.

What types of drugs are used in hormone therapy?

Several types of hormone therapy can be used to treat breast cancer in women. Although many of these may work in men with breast cancer, they often haven’t been studied as well in men.

Some of these drugs might be given along with a targeted drug known as a CDK4/6 inhibitor to help them work better.

Tamoxifen and toremifene

These drugs are known as selective estrogen receptor modulators (SERMs). They block estrogen receptors on breast cancer cells, which can help keep the cells from growing. Both of these drugs are taken daily as pills.

Tamoxifen is the best-studied hormone drug for breast cancer in men and is the drug most often used first.

Large studies of women with early-stage, hormone receptor-positive cancers have shown that taking tamoxifen after surgery for 5 years lowers the chances of the cancer coming back by about half. Taking it for 10 years may help even more.

Studies in men with breast cancer have been smaller, but they have also found that taking tamoxifen after surgery for early-stage breast cancer can lower the chance of the cancer coming back and improve survival.

Tamoxifen can also be used to treat metastatic breast cancer.

Toremifene (Fareston) works like tamoxifen, but it's not used as often and is only approved to treat metastatic breast cancer. It is not likely to work if tamoxifen has already been used and has stopped working.

Possible side effects of tamoxifen and toremifene

The most common side effects of tamoxifen and toremifene are:

• Hot flashes
• Sexual problems
• Fatigue

Some men with bone metastases (cancer spread to the bones) may have a tumor flare (the tumor getting bigger for a short time), which can cause bone pain. This usually goes away quickly, but in rare cases it can also cause hypercalcemia (a high calcium level in the blood) that is hard to control. If this happens, the treatment may need to be stopped for a time.

Rare, but more serious side effects are also possible:

• Blood clots are an uncommon but serious side effect. They usually form in the legs (deep vein thrombosis or DVT), but sometimes a piece of clot may break off and end up blocking an artery in the lungs (pulmonary embolism or PE). Call your doctor or nurse right away if you develop pain, redness, or swelling in your lower leg (calf), shortness of breath, or chest pain, because these can be symptoms of a DVT or PE.
• Rarely, tamoxifen has been associated with strokes in post-menopausal women. The risk in men is not clear. Tell your doctor if you have a sudden severe headache, confusion, or trouble speaking or moving.
• The risk of cataracts (clouding of the lens of the eye) might be slightly higher in people taking tamoxifen. It’s important to tell your doctor right away if you are having any new trouble with your eyesight.

Tamoxifen may also increase the risk of heart attacks in some people, although this link is not clear.

Selective estrogen receptor degraders (SERDs)

Like SERMs, these drugs attach to estrogen receptors. But SERDs bind to the receptors more tightly and cause them to be broken down (degraded).

When used to treat breast cancer in men, these drugs are most often given along with a luteinizing hormone-releasing hormone (LHRH) agonist, which helps turn off hormone production by the testicles (see below).

Fulvestrant (Faslodex) can be used to treat metastatic breast cancer, most often after other hormone drugs (like tamoxifen and often an aromatase inhibitor) have stopped working. It is given by injection into the buttocks every 2 weeks for a month, then monthly.

Elacestrant (Orserdu) or imlunestrant (Inluriyo) can be used to treat advanced, ER-positive, HER2-negative breast cancer when the cancer cells have an ESR1 gene mutation, and the cancer has grown after at least one other type of hormone therapy. These drugs are taken daily as pills.

Possible side effects of SERDs

The most common side effects of these drugs are:

• Hot flashes
• Nausea
• Muscle or joint pain
• Headache
• Feeling tired
• Loss of appetite
• Pain at the injection site

Elacestrant and imlunestrant can also increase cholesterol and fat levels in the blood.

Aromatase inhibitors (AIs)

Aromatase inhibitors (AIs) stop estrogen production by blocking an enzyme (aromatase) in fat tissue that converts male hormones from the adrenal glands into estrogen. They include:

• Anastrozole (Arimidex)
• Letrozole (Femara)
• Exemestane (Aromasin)

These drugs are taken daily as pills.

AIs are effective in treating breast cancer in women, but they have not been well studied in men. Still, some doctors use them to treat advanced breast cancer in men, often combined with a luteinizing hormone-releasing hormone (LHRH) agonist to turn off hormone production by the testicles (discussed below).

These drugs are generally not the first option for men with breast cancer, but one of them might be used if tamoxifen isn’t an option or if it stops working.

Possible side effects of aromatase inhibitors

The main side effects of AIs are:

• Thinning of the bones. Sometimes this might lead to osteoporosis or even bone fractures. If you are taking an AI, you may also be given medicine to help strengthen your bones, such as a bisphosphonate (like zoledronic acid) or denosumab.
• Pain and stiffness in muscles and joints. This may feel like having arthritis in many joints at the same time.

Luteinizing hormone-releasing hormone (LHRH) agonists

In men, LHRH agonists (also called LHRH analogs, GnRH agonists, or GnRH analogs) cause the pituitary gland to turn off production of hormones by the testicles, including testosterone and the small amounts of estrogen made there. Examples of LHRH agonists include:

• Leuprolide (Lupron)
• Goserelin (Zoladex)

LHRH agonists are given as shots, typically either monthly or every few months.

When used to treat breast cancer in men, these drugs are often combined with another hormone therapy, such as an AI or a SERD (see above).

Possible side effects of LHRH agonists

LHRH agonists lower levels of testosterone in men, which can lead to side effects such as:

• Reduced or absent sexual desire
• Erectile dysfunction
• Shrinkage of testicles and penis
• Hot flashes, which may get better or go away with time
• Osteoporosis (bone thinning), which can lead to broken bones
• Anemia (low red blood cell counts)
• Decreased mental sharpness
• Loss of muscle mass
• Weight gain
• Fatigue
• Increased cholesterol levels
• Depression or mood swings

Megestrol

Megestrol (Megace) is a progesterone-like drug. It is unclear how it stops cancer cells from growing, but it appears to compete for hormone receptor sites in the cells. This is an older drug and is usually reserved for men whose cancer is no longer responding to other forms of hormone therapy.

Possible side effects of megestrol

Megestrol may increase the risk for blood clots and frequently causes weight gain by increasing appetite.

Orchiectomy (castration)

Surgical removal of the testicles (orchiectomy) greatly lowers the levels of testosterone and other androgens (male hormones) and is another way to regulate hormones that might affect breast cancer growth. It works in 2 ways:

• Most male breast cancers have androgen receptors that can help the cells to grow.
• Androgens can also be converted into estrogens in the body, so orchiectomy can help lower these levels.

Orchiectomy shrinks most male breast cancers, and it may help make other hormone treatments more likely to work.

This was once a common treatment for breast cancer in men, but it is now used less often because there are now other, less permanent ways to lower hormone levels (such as LHRH agonists – see above).

Possible side effects of orchiectomy

The side effects of orchiectomy are largely due to lower levels of testosterone and are generally the same as those for LHRH agonists (see above).

Some men may be concerned about how they will look after this surgery. If wanted, artificial testicles that look much like natural ones can be placed in the scrotum.