Hormone therapy for breast cancer in men

Hormone therapy is another form of systemic therapy. Like chemotherapy, hormone therapy can be used as an adjuvant therapy to help reduce the risk of cancer recurrence after surgery, and it can be used as neoadjuvant treatment, as well. It is also used to treat cancer that has come back after treatment (recurred) or has spread.

Some breast cancers grow in response to the hormone estrogen. Estrogen is usually thought of as a female hormone, but men have it in their bodies as well, just at lower levels. About 9 out of 10 breast cancers in men have hormone receptors on the surface of their cells. That means, their cancers are estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive. This makes them more likely to respond to hormone treatments. Hormone therapy does not help patients whose tumors are both ER- and PR-negative.

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, doctors have the most experience with using anti-estrogen drugs, such as tamoxifen, in men.

For metastatic breast cancer, hormonal treatments are often used in a sequence. For example, tamoxifen may be tried first. If the cancer does not respond or if it grows back after it first responds, other hormonal treatments may be tried.

Tamoxifen and toremifene (Fareston^®)

These anti-estrogen drugs work by temporarily blocking estrogen receptors on breast cancer cells, preventing estrogen from binding to them and spurring their growth. They are taken daily as a pill.

For someone with a hormone receptor-positive cancer, taking tamoxifen after surgery for 5 years reduces the chances of the cancer coming back by about half. Tamoxifen can also be used to treat metastatic breast cancer. Toremifene works like tamoxifen, but is not used as often and is only approved for patients with metastatic breast cancer.

The most common side effects include fatigue, hot flashes, and sexual problems. Blood clots, which usually form in deep veins of the leg (called deep venous thrombosis or DVT), are a rare but serious side effect of these drugs. In some cases, a piece of clot may break off and end up causing a blockage in the lungs (called a 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.

Tamoxifen has rarely been associated with strokes. These mostly have been seen in post-menopausal women, and the risk in men is not clear. Still, 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 patients, however this link is not clear.

Aromatase inhibitors

This group of drugs includes anastrozole (Arimidex^®), letrozole (Femara^®), and exemestane (Aromasin^®). They block the production of small amounts of estrogen by the adrenal glands. Aromatase inhibitors are taken daily as pills. They have been found to be 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 either after a drug like tamoxifen stops working or even as the first line of hormone therapy instead of tamoxifen. Clinical trials are also looking at using aromatase inhibitors along with LHRH analogs (these are discussed later on). The main side effects of these drugs are thinning of the bones and joint and muscle pain.

Fulvestrant (Faslodex^®)

Fulvestrant is a drug that also acts on the estrogen receptor, but instead of blocking it, this drug eliminates it. In women, this drug is often effective even if the breast cancer is no longer responding to tamoxifen. It has not been studied in men with breast cancer. It is given by injection once a month. Hot flashes, mild nausea, and fatigue are the major side effects. It is currently only approved by the Food and Drug Administration (FDA) for use in post-menopausal women with advanced breast cancer that no longer responds to tamoxifen or toremifene, but it may help men with breast cancer as well.

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

LHRH analogs such as leuprolide (Lupron^®) and goserelin (Zoladex^®) affect the pituitary gland and, stop the signal that the body sends to the testicles to make androgens. They cause androgen levels in the body to go down. They are given as shots either monthly or every few months. 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. LHRH analogs, either alone or with anti-androgens, are often effective in shrinking male breast cancers.

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 greatly lowers the levels of testosterone and other androgens (male hormones) in the body. Most male breast cancers contain 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 may help other treatments like tamoxifen more likely to work. This treatment was once quite common, but it is now used less often because of new non-surgical approaches to lowering androgen levels, such as the LHRH analogs discussed previously.

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 having an erection, 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.