Hormone Therapy for Breast Cancer in Men
Hormone therapy is the use of hormones or drugs or other treatments that affect hormones in treating cancer. 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, or as neoadjuvant treatment. 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 of 10 breast cancers in men are hormone receptor-positive (either 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 people 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, they often haven’t been studied well, if at all. The anti-estrogen drug, 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.
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.
Large studies of women with hormone receptor-positive cancers removed completely with surgery, show 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 indicate 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 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.
This group of drugs includes anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®). They work 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 releasing hormone analog to turn off hormone production by the testicles (these drugs are discussed later on). These drugs are generally used if tamoxifen stops working. They are also sometimes used as the first line of hormone therapy instead of tamoxifen, but this has been linked to poorer outcomes. The main side effects of these drugs are thinning of the bones and joint and muscle pain.
Fulvestrant is a drug that also acts on the estrogen receptor, but instead of blocking it, this drug eliminates it. In postmenopausal women, this drug is often effective even if the breast cancer is no longer responding to tamoxifen. In one small study of men with advanced breast cancer who had previously been treated with at least one other hormone drug, some of the men saw their tumors shrink with fulvestrant. It is given by injection every 2 weeks for a month, then monthly. The most common side effects are hot flashes, mild nausea, fatigue, and pain at the injection site.
Luteinizing hormone-releasing hormone (LHRH) analogs and anti-androgens
LHRH analogs such as leuprolide (Lupron®) and goserelin (Zoladex®) affect the pituitary gland. In men they turn off production of the male hormone 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 (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.
Surgical removal of 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 may help make 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.
Last Medical Review: October 10, 2014 Last Revised: January 26, 2016
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