Breast cancer
Description
An in-depth report on the causes, diagnosis, treatment, and prevention of breast cancer.
Alternative Names
Mammograms; Mastectomy
Hormone Therapy
Hormone therapy works by blocking estrogen that causes cell-proliferation. It is used for adjuvant therapy and for advanced cancers in patients with hormone receptor-positive tumors. Over the past few years, many new anti-estrogen drugs have become available. Generally they do one or more of the following:
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Block the hormone receptor itself
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Suppress estrogen production
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Destroy the ovaries (which produce estrogen)
Tamoxifen and Selective Estrogen Receptor Modulators (SERMs)
Tamoxifen (Nolvadex) has been the standard hormonal drug used for breast cancer. It is the prototype for a growing class of compounds called selective estrogen receptor modulators (SERMs). SERMs chemically resemble estrogen and trick the breast cancer cells into accepting it in place of estrogen. Unlike estrogen, however, they do not stimulate breast cancer cell growth. Other SERMs being studied for breast cancer include toremifene (which is very similar to tamoxifen), idoxifene, and droloxifene.
Candidates.
Tamoxifen is used for any cancer stage in women of all ages who have hormone receptor-positive cancers. In addition, it is being used to protect against cancer in high-risk women.
Tamoxifen as Adjuvant Therapy.
When used as adjuvant therapy for early stage hormone receptor positive breast cancer, tamoxifen is well-tolerated for 5 years. Evidence shows that taking it for 5 years significantly improves survival rates and reduces recurrence. Taking it longer appears to confer no additional advantages. Patients whose tumors are convincingly hormone receptor-negative do not benefit. Comparisons between tamoxifen and other SERMs used for adjuvant therapy are underway.
Side Effects.
Hormone therapy with SERMs has fewer side effects than chemotherapy, but can still cause hot flashes, vaginal bleeding and discharge, and visual disturbances.
Of concern is an increased risk for blood clots, which can, in rare cases, be life-threatening. Tamoxifen, and possibly toremifene, pose a long-term increased risk for uterine (endometrial), cancer, though not enough to offset the benefits from breast cancer prevention. Any woman on tamoxifen with vaginal bleeding should see her doctor immediately to rule out uterine cancer. Early evidence indicates that some of the newer SERMs may not increase the risk for uterine cancer. Long-term studies are needed.
Endometrial cancer is a cancerous growth of the endometrium (lining of the uterus). It is the most common uterine cancer.
Aromatase Inhibitors
Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues including the breast, muscle, liver, and fat. These drugs are showing great promise for treating hormone receptor-positive (also called estrogen-sensitive, hormone-sensitive, or hormone-responsive) breast cancer.
There are currently three aromatase inhibitors approved for treating early-stage, hormone receptor-positive breast cancer in postmenopausal women:
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Anastrazole (Armidex)
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Exemestane (Aromasin)
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Letrozole (Femara)
Armidex and Letrozole are approved for treatment after surgery. Exemestane is approved for women who have taken tamoxifen for 2 - 3 years. These drugs are also approved for women with advanced (metastatic) hormone-sensitive breast cancer.
Tamoxifen is another drug used to treat estrogen-sensitive breast tumors, but it works in a different way than aromatase inhibitors. Tamoxifen interferes with tumors’ ability to use estrogen by blocking their estrogen receptors. Aromatase inhibitors reduce the overall amount of estrogen in the body.
Compared to tamoxifen, aromatase inhibitors are less likely to cause blood clots and uterine cancer. However, these drugs are more likely to cause osteoporosis, which can lead to bone loss and fractures. In general, recent studies indicate that aromatase inhibitors may be better than tamoxifen in improving survival in women with hormone-sensitive breast cancer (especially for those with node-positive cancer) and reducing the risk of cancer recurrence.
Selective Estrogen Receptor Downregulators (SERDs)
Selective estrogen receptor downregulators (SERDs) block estrogen in all tissues in the body. Fulvestrant (Faslodex) is one such drug, which is proving to be at least as effective as anastrozole in delaying time to disease progression in women with advanced breast cancer. Side effects generally include gastrointestinal problems and hot flashes.
Progestins
Progestins, particularly megestrol (Megace), have been used as second- or third-line treatment of advanced breast cancer when tamoxifen fails. Some of the aromatase inhibitors, however, are proving to be more effective, and some have fewer side effects, such as weight gain.
Ovarian Ablation
Ovarian ablation literally shuts down estrogen production from the ovaries. Medications can accomplish ovarian ablation, or it can be done by destroying the ovaries with surgery or radiation. (Osteoporosis is one serious side effect of this approach, but several therapies are available to help prevent bone loss.)
Chemical Ovarian Ablation.
Drug treatment (non-chemotherapy drugs) to block ovarian production of estrogen is called chemical ovarian ablation. It is often reversible. The primary drugs used are luteinizing hormone-releasing hormone (LHRH) agonists, such as goserelin (Zoladex). (They are also sometimes called GnRH agonists). These drugs block the release of the reproductive hormones LH-RH, which results in the cessation of ovulation and estrogen production.
Studies suggest that women with estrogen-positive early stage cancer who take goserelin have similar survival rates to those who take standard chemotherapy and they experience fewer serious side effects. A major analysis of four trials using LHRH agonists plus tamoxifen also suggested that this combination should be the standard for patients with advanced breast cancers that are hormone-receptor positive, although this is an area of controversy. (Chemotherapy is still more effective in women with estrogen-negative tumors.)
Ovariectomy.
Ovariectomy, the removal of the ovaries, has modestly improved breast cancer survival rates in some premenopausal women whose tumors are hormone receptor-positive. In these women, combining this procedure with tamoxifen may improve results beyond those of standard chemotherapies. Ovariectomy does not benefit women after menopause, and its advantages can be blunted in women who have received adjuvant chemotherapy. The procedure causes sterility and can have a major negative emotional impact on younger patients.
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Review Date: 4/3/2007
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Reviewed By: Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, M.D., Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (10/2/2006).
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