Harmone Therapy

The hormone estrogen is produced mainly by a woman's ovaries until menopause, and then by conversion of a testosterone-like hormone made by the adrenal gland, which is then converted into estrogen mostly in the body’s fat tissue. Estrogen promotes the growth of about two thirds of breast cancers (those containing estrogen or progesterone receptors). Because of this, several approaches to blocking the effect of estrogen or lowering estrogen levels are used to treat breast cancer.

Tamoxifen: The antiestrogen drug that has been used most often is tamoxifen (Nolvadex). It is taken daily in pill form. Taking tamoxifen after surgery, usually for 5 years, reduces the chances of the cancer coming back by about 50% for women with early breast cancer if the cancer contained estrogen or progesterone receptors. Tamoxifen is also used to treat metastatic breast cancer. It is used to prevent the development of breast cancer in a woman at high risk, as well.

Tamoxifen can increase the risk of developing cancer of the lining of the uterus (endometrial cancer). This cancer is usually diagnosed at a very early stage and is generally curable by surgery. Tamoxifen can also increase the risk of uterine sarcoma, a rare cancer of the connective tissue of the uterus. If you are taking tamoxifen, tell your doctor right away about any unusual vaginal bleeding (a common symptom of both of these cancers). Most uterine bleeding is not due to cancer, but this symptom always needs prompt evaluation.

Blood clots are another serious side effect of tamoxifen. Other side effects of tamoxifen may include weight gain (although recent studies have not found this), hot flashes, vaginal discharge, and mood swings. Early cataracts may occur rarely. Nonetheless, for most women with breast cancer, the benefits of taking tamoxifen far outweigh the risks.

Some patients whose cancer has spread to their bones may experience a "tumor flare" with pain and inflammation in the muscles and bones when treated with tamoxifen. It usually subsides quickly. However, 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.

Aromatase inhibitors: Three drugs that stop estrogen production in postmenopausal women have been approved for use in treating both early and advanced breast cancer. These drugs are called letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin). They work by blocking an enzyme responsible for producing small amounts of estrogen in postmenopausal women. They cannot stop the ovaries of premenopausal women from producing estrogen. For this reason they are only effective in postmenopausal women.

These drugs have been compared with tamoxifen as adjuvant hormone therapy in postmenopausal women with early breast cancer. Clinical trials have been performed comparing tamoxifen with one of the aromatase inhibitors “head to head” for a total of 5 years, or after either 2 years or 5 years of tamoxifen. In each of these studies there has been a clear advantage to using either the aromatase inhibitor instead of tamoxifen for a total of 5 years or following several years of tamoxifen rather than keeping women on tamoxifen for 5 years as their only hormone therapy. Clinical trials continue to be done to try and figure out which of these strategies is the best. The aromatase inhibitors have fewer side effects than tamoxifen because they don’t cause endometrial cancer and very rarely cause blood clots. They can, however, cause osteoporosis and bone fractures because they remove all estrogens from a postmenopausal woman.

Many doctors prefer aromatase inhibitors over tamoxifen as the first hormonal treatment for postmenopausal women whose breast cancer has come back, if the cancer is hormone receptor positive.

Raloxifene: Raloxifene (Evista) is a drug that, like tamoxifen, blocks the effect of estrogen on breast tissue and breast cancer. It was originally developed to treat osteoporosis because it has the same bone strengthening effect as estrogen. But in other ways it is an antiestrogen. It is currently being tested to see if it can reduce women's risk of developing breast cancer. Until more testing is done, raloxifene is not recommended as hormonal therapy for women who have already been diagnosed with breast cancer.

Toremifene: Toremifene (Fareston), another antiestrogen drug closely related to tamoxifen, may be an option for postmenopausal women with breast cancer that has metastasized. Toremifene is an antiestrogen medicine that is used in tumors that are estrogen-receptor positive or whose estrogen-receptor status is unknown.

Fulvestrant: Fulvestrant (Faslodex) is a newly approved drug that also acts via 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 only given to women who are already in menopause.

Ovarian ablation: Removing estrogens from premenopausal women is another effective way of treating breast cancer in hormone-responsive cancer. This can be done surgically, by removing the ovaries. It also can be done with drugs called luteinizing hormone-releasing hormone (LHRH) analogs. The usual drugs are goserelin or leuprolide. These drugs block the mechanism that causes ovaries to make estrogens. They are now being tested as adjuvant therapies. Chemotherapy drugs may also damage the ovaries of premenopausal women so they no longer produce estrogen.

Megestrol acetate: Megestrol acetate (Megace) is a progesterone-like drug used for 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.

Other ways to control hormones: Androgens (male hormones) may be considered after other hormone treatments for advanced breast cancer have been tried. Androgens cause masculine characteristics to occur, for example, more body hair and a deeper voice. They are sometimes effective.

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