Hormone therapy is another form of systemic therapy. It is most often used as an adjuvant therapy to help reduce the risk of cancer recurrence after surgery, although it may also be used for more advanced breast cancers.

A woman's ovaries are the main source of the hormone estrogen up until menopause. After menopause, smaller amounts are still made in the body's fat tissue, where a hormone made by the adrenal gland is converted into estrogen.

Estrogen promotes the growth of about 2 out of 3 of breast cancers -- those containing estrogen receptors (ER-positive cancers) and/or progesterone receptors (PR-positive cancers). Because of this, several approaches to blocking the effect of estrogen or lowering estrogen levels are used to treat ER-positive and PR-positive breast cancers. Hormone therapy does not help patients whose tumors are both ER- and PR-negative.

Tamoxifen and toremifene (Fareston): These anti-estrogen drugs work by temporarily blocking estrogen receptors on breast cancer cells, preventing estrogen from binding to them. They are taken daily as a pill.

For women with ER- or PR-positive cancers, 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, as well as to reduce the risk of developing breast cancer in women at high risk.

Toremifene is used mainly in post-menopausal women with advanced cancers that are ER- positive (or whose ER status is unknown).

The most common side effects of these drugs include fatigue, hot flashes, vaginal discharge, and mood swings.

Some patients whose cancer has spread to their bones may experience a "tumor flare" with pain and swelling in the muscles and bones. This usually subsides quickly, but in some cases the patient may also develop a high calcium level in the blood that cannot be controlled. If this occurs, the treatment may need to be stopped.

Rare, but more serious side effects are also possible. These drugs can increase the risk of developing cancers of the uterus (endometrial cancer and uterine sarcoma). Tell your doctor right away about any unusual vaginal bleeding (a common symptom of both of these cancers). Most uterine bleeding is not from cancer, but this symptom always needs prompt attention.

Another possible serious side effect is blood clots, which usually form in the legs. In some cases, these may lead to a heart attack, stroke, or blockage in the lungs (pulmonary embolism). Call your doctor or nurse right away if you develop pain, redness, or swelling in your lower leg (calf), shortness of breath, chest pain, sudden severe headache, confusion, or trouble speaking or moving.

Depending on a woman's menopausal status, tamoxifen can have different effects on the bones. In pre-menopausal women tamoxifen can cause some bone thinning, but in post-menopausal women it is often good for bone strength. The effects of toremifene on the bones are less clear.

For most women with breast cancer, the benefits of taking these drugs outweigh the risks.

Fulvestrant (Faslodex): Fulvestrant is a drug that also acts on the estrogen receptor, but instead of blocking it, this drug eliminates it. It is often effective even if the breast cancer is no longer responding to tamoxifen. It is given by injection once a month. Hot flashes, mild nausea, and fatigue are the major side effects. It is currently only approved for use in post-menopausal women with advanced breast cancer that no longer responds to tamoxifen or toremifene.

Aromatase inhibitors: Three drugs that stop estrogen production in post-menopausal women have been approved to treat both early and advanced breast cancer: letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin). They work by blocking an enzyme (aromatase) responsible for making small amounts of estrogen in post-menopausal women. They cannot stop the ovaries of pre-menopausal women from making estrogen, so they are only effective in post-menopausal women. These drugs are taken daily as pills.

Several studies have compared these drugs with tamoxifen as adjuvant hormone therapy in post-menopausal women. Using these drugs, either alone or after tamoxifen, has been shown to better reduce the risk of cancer recurrence compared to using just tamoxifen alone for 5 years.

For post-menopausal women whose cancers are estrogen and/or progesterone receptor-positive, most doctors now recommend using an aromatase inhibitor at some point during adjuvant therapy. But several important questions have not yet been answered. For example, it's not clear if starting adjuvant therapy with one of these drugs is better than giving tamoxifen and then switching to an aromatase inhibitor. If tamoxifen is given first, it's not clear how long it should be given. The optimal length of treatment with aromatase inhibitors has not yet been determined, nor has it been shown if any one of these drugs is better than the others. Studies now being done should help answer these questions.

The aromatase inhibitors tend to have fewer serious side effects than tamoxifen -- they don't cause uterine cancers and very rarely cause blood clots. They can, however, cause joint stiffness and/or pain, similar to a new feeling of having arthritis in many different joints at one time. They can also cause bone thinning (osteoporosis) and fractures because they remove all estrogens from a post-menopausal woman. Patients treated with an aromatase inhibitor may want to ask their doctor if they should have their bone strength tested (called a bone density test) to determine if they need medicine, such as bisphosphonates, to strengthen their bones.

Ovarian ablation: In pre-menopausal women, removing or shutting down the ovaries, which are the main source of estrogens, effectively makes the woman 'post-menopausal'. This may allow some other hormone therapies to work better.

Ovarian ablation can be done surgically (and permanently) by removing the ovaries. This operation is called an oophorectomy. It also can be done with drugs called luteinizing hormone-releasing hormone (LHRH) analogs, such as goserelin (Zoladex) or leuprolide (Lupron). These drugs block the mechanism that causes the ovaries to make estrogens. They are now being tested as adjuvant therapies along with tamoxifen or an aromatase inhibitor in pre-menopausal women.

Chemotherapy drugs may also damage the ovaries of pre-menopausal women so they no longer produce estrogen. This can sometimes be a helpful (if unintended) consequence of chemotherapy with regard to breast cancer treatment, although it leaves the woman infertile.

All of these methods can cause a woman to have symptoms of menopause, including hot flashes, night sweats, vaginal dryness, and mood swings.

Megestrol acetate: Megestrol acetate (Megace) is a progesterone-like drug used as a hormone treatment of advanced breast cancer, usually for women whose cancers do not respond to the other hormone treatments. Its major side effect is weight gain, and it is sometimes used to reverse weight loss in patients with advanced cancer. This is an older drug that is no longer used very often.

Other ways to control hormones: Androgens (male hormones) may be considered after other hormone treatments for advanced breast cancer have been tried. They are sometimes effective, but they can cause masculine characteristics such as an increase in body hair and a deeper voice to develop.

Last Medical Review: 09/04/2008
Last Revised: 05/13/2009