Hormone Therapy for Breast Cancer in Men

Hormone therapy (sometimes called endocrine therapy) is a way to treat cancer by using hormones or drugs or other treatments that affect hormones. Hormone therapy is a form of systemic therapy, meaning it can reach nearly all parts of the body.

Hormone therapy can be used after surgery (adjuvant therapy) to help lower the risk of cancer coming back, or before surgery (neoadjuvant treatment). It can also be used to treat cancer that has spread, or cancer that has come back after treatment (recurred).

Some breast cancers grow in response to the hormones estrogen or progesterone. Estrogen and progesterone are usually thought of as female hormones, but men have them in their bodies, too, just at lower levels.

About 9 of 10 breast cancers in men are hormone receptor-positive, meaning they are estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, or both. This makes them more likely to respond to hormone treatments. Hormone therapy does not help people whose tumors are both ER- and PR-negative.

What types of drugs are used in hormone therapy?

Several approaches to blocking the effects of estrogen or lowering estrogen levels are used to treat breast cancer in women. Although many of these may work in men as well, they often haven’t been studied well, if at all.

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 most often used first. If tamoxifen doesn’t work (or stops working), other hormone drugs may be tried, but this is largely based on how well they work in women with breast cancer.

Large studies of women with early-stage, hormone receptor-positive cancers have shown that taking tamoxifen after surgery for 5 years reduces 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.

The most common side effects of tamoxifen and toremifene are:

• Hot flashes
• Sexual problems
• Fatigue

Some men with cancer spread to the bones may have a tumor flare with pain and swelling in the muscles and bones. This usually goes away quickly, but rarely a man may also develop 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 another uncommon, but serious side effect. They usually form in the legs (called 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.

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).

Fulvestrant (Faslodex) is 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) 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. This drug is taken daily as pills.

The most common side effects of these drugs are hot flashes, nausea, muscle or joint pain, headache, and pain at the injection site. Elacestrant can also increase cholesterol and fat levels in the blood.

Aromatase inhibitors

This group of drugs includes anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin). These drugs stop estrogen production by blocking an enzyme (aromatase) in fat tissue that converts male hormones from the adrenal glands into estrogen.

Aromatase inhibitors are taken daily as pills. They have been very 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) analog to turn off hormone production by the testicles (discussed below). These drugs are generally used if tamoxifen stops working. 

The main side effects are thinning of the bones and pain in muscles and joints.

Luteinizing hormone-releasing hormone (LHRH) analogs and anti-androgens

In men, LHRH analogs such as leuprolide (Lupron) and goserelin (Zoladex) affect the pituitary gland, which regulates testosterone production in the testicles. These drugs cause the pituitary gland to turn off production of testosterone by the testicles, leading to lower testosterone levels. They are given as shots either monthly or every few months. These drugs may be used by themselves, or combined with aromatase inhibitors or anti-androgens to treat advanced breast cancer in men.

Anti-androgens such as flutamide and bicalutamide work by blocking the effect of male hormones on breast cancer cells. These drugs are taken daily as pills.

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 that is usually reserved for men who are no longer responding to other forms of hormone therapy. Megestrol may increase the risk for blood clots and frequently causes weight gain by increasing appetite.

Orchiectomy (castration)

Surgical removal of the testicles (orchiectomy) is another way to regulate hormones that might affect breast cancer growth. Removing the testicles greatly lowers the levels of testosterone and other androgens (male hormones). Most male breast cancers have androgen receptors that may cause the cells to grow. Androgens can also be converted into estrogens in the body.

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

This was once a common treatment for breast cancer in men, but it is now used less often because medicines such as LHRH analogs can now be used to lower androgen levels.

Possible side effects of hormone therapy

Although some of these drugs have unique side effects (see descriptions above), in general they can cause loss of sexual desire, trouble getting erections, weight gain, hot flashes, and mood swings. Be sure to discuss any such side effects with your cancer care team because there may be ways to treat them.