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Hormonal Therapy for Breast Cancer
This page discusses the use of hormonal therapy for the treatment of breast cancer. For a thorough review of hormonal therapy for cancer treatment, please see the hormonal therapy treatment monograph .
Hormones are chemical messengers that regulate specific body functions, such as reproduction. They are produced by various glands in the body and enter the blood stream, where they travel to other tissues and exert their influence. Hormonal therapy is used in cancer treatment to augment or interfere with the activity of certain hormones that can influence the growth of tumors.
Who Can Benefit from Hormonal Therapy
Certain hormones, such as estrogen and progesterone, can “feed” certain types of breast cancer cells—cancer cells that have receptors for estrogen or progesterone.
Breast cancers that have estrogen receptors or progesterone receptors are said to be "estrogen or progesterone receptor-positive" or "hormone sensitive." Those breast cancers that do not have either estrogen or progesterone receptors are "hormone receptor-negative." In women with hormone-sensitive cancers, cancer cell growth is under the control of estrogen. Therefore, such cancers can often be treated with drugs that reduce or stop the effects of estrogen. Hormone receptor-negative cancer cells are not receptive to these types of drugs.
Laboratory tests called tissue staining can determine if a cancer is sensitive to hormones. Any tissue staining for estrogen or progesterone receptors (above 0%) indicates that hormonal therapy may be effective. Women whose cancers do not stain for hormone receptors at all (0%) do not appear to benefit from hormonal therapy, either to prevent recurrence, or to prevent second cancers.
In the treatment of early stage cancers, hormonal therapy is used to prevent cancer from spreading to other areas and to lower the risk of a second, independent breast cancer. Woman cured of one breast cancer have a higher incidence of second unrelated cancers than women who have never had breast cancer.
Talk with Your Doctor about this Treatment
While the vast majority of women who have hormone-sensitive breast cancer will benefit from hormonal therapy, there may be times when the risks may outweigh the potential benefits. Your physician will help you weigh the risks and benefits.
Methods of Hormonal Therapy
The goal of hormonal therapy is to prevent hormones from helping cancer cells grow. This may be done in a number of ways:
- Blocking the function of hormones; done with drugs
- Suppressing hormone production in the ovaries, which is called ovarian ablation; this can be done with drugs, radiation, or with surgery
- Suppressing the production of hormones outside of the ovary by other tissues; done with drugs
There are several classes of hormonal therapy drugs:
Selective Estrogen Receptor Modulators (SERMs)
A commonly used selective estrogen receptor modulator (SERM) is raloxifene (Evista). This drug is used to treat osteoporosis. In women with osteoporosis who have been treated with raloxifene, this drug has been shown to reduce the risk of breast cancer. Raloxifene is generally taken by mouth in tablet form on a daily basis.
Raloxifene is not yet approved for use in breast cancer treatment. Its benefits, compared to tamoxifen ( discussed below ), are being evaluated in the STAR prevention trial. Some reports have found a lower risk of uterine cancer among women taking raloxifene as compared with women taking tamoxifen. The development of uterine cancer is known to be influenced by estrogen-like activity. Raloxifene has been associated with an increased risk of blood clots.
Aromatase inhibitors work by inhibiting the conversion of androgens into estrogens. Androgens are commonly referred to as male hormones, but they are found in both men and women. A small amount of androgen is continuously converted into estrogen by the enzyme aromatase. Aromatase inhibitors block the action of aromatase, leaving less estrogen available to stimulate estrogen receptors on cancer cells.
Aromatase inhibitors are used primarily in postmenopausal women.
Drugs in this class include:
- Letrozole (Femara)
- Anastrozole (Arimidex)
- Exemestane (Aromasin)
Effectiveness and Side Effects of Aromatase Inhibitors
Until recently, these medications have been used in advanced stage breast cancers, but researchers are now examining their effectiveness for prevention of recurrence and second breast cancer events. In early results of one large multicenter trial (the ATAC trial), the aromatase inhibitor anastrazole was superior in preventing second breast cancer events and recurrence compared to tamoxifen or the combination of anastrazole and tamoxifen. In addition, aromatase inhibitors do not appear to have the same risk of uterine cancer, blood clots, or vascular events associated with tamoxifen; however, bone thinning and hip fractures may occur more often with aromatase inhibitors.
Studies have also suggested that aromatase inhibitors may be equally if not more effective than tamoxifen in treating early-stage and advanced cases of breast cancer. More research is being conducted to determine long-term effectiveness.
The primary side effect of aromatase inhibitors is an increased risk of osteoporosis (including bone thinning and hip fractures). Therefore, women who use aromatase inhibitors need to have their bone densities measured on a regular basis, and may be prescribed measures to improve bone density such as bisphosphonates, calcium, vitamin D, or exercise.
Estrogen Receptor Down-regulators
Estrogen receptor down-regulators bind to estrogen receptors on cancer cells and block the receptors so that estrogen cannot enter the cancer cell. This is a complicated process, as certain drugs can act as blockers in one tissue or situation and act like estrogen in other tissues or situations. Two drugs in this class are tamoxifen and fulvestrant.
Tamoxifen (Nolvodex) is used for both treatment and prevention of breast cancer. Tamoxifen has both estrogen-like (agonist) and estrogen-blocking (antagonist) effects. Tamoxifen is generally taken by mouth in tablet form on a daily basis.
Tamoxifen has been approved by the FDA to treat women with breast cancer for more than 20 years and has been in clinical trials for about 30 years. Tamoxifen has been the standard treatment for women with estrogen-sensitive breast cancer. However, new studies suggest that aromatase inhibitors may be equally if not more effective than tamoxifen in treating early-stage and advanced cases of breast cancer. More research is being conducted to determine long-term effectiveness.
Possible side effects and complications associated with tamoxifen include the following:
- Blood clots
- Endometrial changes, such as hyperplasia
- Endometrial or uterine cancer
A newer drug that works in a similar fashion to tamoxifen is fulvestrant. Fulvestrant, like tamoxifen, attaches to the estrogen receptor but, unlike tamoxifen, it destroys the receptor, thereby blocking all estrogen activity. This drug is given once a month by intramuscular injection for as long as it is beneficial in the treatment of advanced disease. It is not yet approved for use as an adjuvant treatment (a treatment that enhances the effects of the primary treatment).
Luteinizing Hormone-releasing Hormone (LHRH) Agonists
Luteinizing hormone (LH) is secreted from cells in the pituitary gland and stimulates the ovaries to produce and secrete estrogen. Luteinizing hormone-releasing hormone (LHRH) agonists are drugs that block the action of LH and therefore block ovarian production of estrogen. LHRH agonists are used for chemical ovarian ablation, which is discussed below .
Other Hormonal Agents, Including Androgens
Androgens (male hormones, such as testosterone), as well as progesterone (female steroid hormones) and progestational agents have been used to treat advanced, hormone-sensitive breast cancer when other medications have not been effective.
Ovarian ablation—suppression of hormone production in the ovaries—reduces the amount of estrogen and progesterone circulating in the body, which, in turn, deprives hormone-sensitive breast tumors of the hormones they need to grow. It is useful for premenopausal women only.
Ovarian ablation may be accomplished by surgery to remove the ovaries, radiation, or drug therapy; however, most physicians today prefer drug therapy, which is called chemical ovarian ablation. This is the preferred method because, unlike surgery and radiation, it is temporary, and fertility may be restored after treatment.
Chemical Ovarian Ablation
The drug used for chemical ovarian ablation is goserelin. Goserelin reduces production of luteinizing hormone (LH) from the pituitary gland, which leads to a reduction of estrogen. This can result in shrinking the tumour, or slowing down the growth of the cancer.
Goserelin is injected under the skin of the upper abdomen every 28 days. This treatment is used primarily in premenopausal women with early stage receptor-positive breast cancer. It is not effective in women who have receptor-negative breast cancer.
Goserelin can be used alone or with other forms of treatment. Studies have shown that in women under age 50 with early breast cancer, ovarian ablation without chemotherapy improves long-term, recurrence-free survival and overall survival by approximately 30%. Recent studies have suggested that ovarian ablation plus tamoxifen many be as effective as chemotherapy in certain cases. Further study is needed to determine if ovarian ablation is more effective when combined with other treatments or when given alone.
The following side effects may occur with hormonal treatment for breast cancer:
- Hot flashes
- Decreased sexual desire
- Weight gain
- Swelling and tenderness of the breasts
- Bone pain
Hormonal Therapy for the Prevention of Breast Cancer
In some women at high risk for breast cancer, hormonal therapy may be given in an attempt to prevent the development of breast cancer. The drugs used in these cases are tamoxifen and raloxifene.
Tamoxifen (Nolvadex) – in the Breast Cancer Prevention Trial, tamoxifen was shown to reduce breast cancer incidence by 49% in women at increased risk of the disease.
Raloxifene (Evista) – in a large study of its use to treat osteoporosis, raloxifene was shown to reduce the incidence of breast cancer. The Multiple Outcomes of Raloxifene Evaluation (MORE), which was a multicenter, randomized, double-blind trial, studied 7,705 postmenopausal women taking raloxifene in two doses or placebo for about 40 months. Among the women in this study who had osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene.
Memorial Sloan Kettering Cancer Center
National Cancer Institute
Susan G. Komen Breast Cancer Foundation
Early Breast Cancer Trialists’ Collaborative Group. Ovarian ablation in early breast cancer: overview of the randomised trials. Lancet. 1996;348:1189-1196.
Harris JR, Lippman ME, Morrow M, Osborne CK. Diseases of the Breast . Philadelphia: Lippincott Williams and Wilkins; 1999.
- Reviewer: Mohei Abouzied, MD
- Review Date: 09/2009