Hormonal therapy is the use of drug therapy to treat breast cancer either in the preventive, post-operative (adjuvant), pre-operative (neoadjuvant) or advanced disease (metastatic) setting. Hormonal therapy is only an option if your breast cancer is Estrogen receptor (ER) or Progesterone receptor (PR) positive.

Hormonal therapy is designed to oppose the estrogen receptor in some fashion. Tamoxifen (Nolvadex) binds to the estrogen receptor and therefore inhibits estrogen from binding to it. Since estrogen binding sets off a cascade of protein production that stimulates breast cancer growth, tamoxifen sets off a cascade of protein production that inhibitis breast cancer growth. Tamoxifen may also have other mechanisms of action such as putting cells into a dormant (non-growing) cycle. Tamoxifen opposes estrogen (i.e., antagonizes) at the level of the breast cell and the breast cancer cell. It may act like estrogen at the level of bone (tamoxifen, like estrogen, can prevent bone fractures), and in the uterus (both drugs are associated with uterine cancer), and both drugs may cause an increased risk of blood clots. Tamoxifen is FDA approved for use in: (a) high risk women to decrease the risk of breast cancer development; (b) in the adjuvant setting to prevent or delay breast cancer recurrence, as clinical trials have shown a survival advantage to its use; and, (c) to treat metastatic or advanced breast cancer. Tamoxifen may also have benefit in the treatment of women with DCIS. Tamoxifen is associated with other side effects, including the development or exacerbation of menopausal symptoms (hot flashes, vaginal discharge, vaginal dryness); leg cramps, abnormal liver function studies, depression (0-2%) and the development of a rare uterine muscle cancer (<1%). In many studies comparing tamoxifen to a placebo (inactive agent), the incidence of weight gain has been the same in both groups. Hair loss or increased facial hair are more a function of menopause, than a direct effect of the tamoxifen. Raloxifene (Evista) and toremifine are chemically similar to tamoxifen. Evista is FDA approved for the prevention of osteoporosis; it is being compared in the STAR trial to tamoxifen to see if it is equal or better as a breast cancer preventive agent. Toremifine is an alternative to tamoxifen as a treatment for advanced disease.

Another class of hormone drugs that are very effective in breast cancer treatment is the adrenal aromatase inhibitors. These drugs actually inhibit the production of estrogen from non-ovarian sources (i.e., breast, muscle, body fat). These drugs are only active in post-menopausal women. Drugs in this class are: anastrozole (Arimidex), letrozole (Femara) and exemestane (Aromasin). These drugs are all FDA approved for treatment of advanced breast cancer and anastrozole and letrozole have been shown to be better than tamoxifen as first line treatment of estrogen responsive metastatic breast cancer. A recent large trial, the ATAC trial, comparing tamoxifen to anastrozole to the combination in women after surgery for breast cancer has shown promising preliminary results and further data will be published. This study did show the anastrozole was associated with a higher risk of bone and joint pains, and more importantly, an increased risk of bone fractures. Small studies are evaluating the role for this class of drugs in preoperative therapy, i.e., to decrease the size of large primary breast cancers in post-menopausal women who may not be good candidates for chemotherapy before surgery. Other side effects include headaches and hot flashes.

A new hormonal approach to treating breast cancer is to decrease (downregulate) the number of estrogen receptors on the cancer cell. A new medication called Faslodex, was FDA approved in 2002 for use in women who have failed other endocrine treatments. Faslodex must be given as an intramuscular injection every 28 days and the major side effects are the volume of injection (sometimes 2 shots are required for each treatment) and hot flashes.

Other hormonal treatments which you may be offered include:

1. LH-RH Agonists - these medications, given as an injection monthly, inhibit the production of estrogen, by acting on the brain to turn off the ovarian production of estrogen; these may play a role in the treatment of metastatic disease in pre-menopausal women and possibly in the post-operative setting; these induce a “chemical menopause” and should be reversible if stopped.
2. Removal of your Ovaries - this treatment may be indicated in pre-menopausal women to permanently remove the major source of ovarian production; this treatment may be used to treat metastatic disease and may be as effective as chemotherapy in the post-operative setting in premenopausal women.
3. Progestational Agents - drugs such as Megace may be active in the treatment of metastatic disease.
4. Male Hormones - drugs such as Halotestin (a testosterone formulation) may be effective in metastatic disease.
5. Estrogen - while this may seem paradoxical, drugs such as DES (dietylystilbestrol) were the most common treatment for breast cancer before the use of tamoxifen; estrogens in higher doses, such as in DES, may actually be an effective treatment for breast cancer.

You should always consult your physician for more information and to discuss any questions that you may have.