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Hormonal therapy for breast cancer
Hormonal therapy is a systemic therapysystemic therapyTreatment that travels through the bloodstream to reach cells all over the body. that slows the growth and spread of breast cancer cells by changing hormone levels in the body, or by stopping breast cancer cells from using estrogen. Hormones are chemical substances that are produced by glands in the body or made in a laboratory. Drugs, surgery or radiation therapy can be used to change hormone levels.
EstrogenEstrogenA female sex hormone that causes the female sex characteristics to develop (such as breasts) and is necessary for reproduction. and progesteroneprogesteroneA female sex hormone that prepares the uterus (womb) for pregnancy and the breasts for lactation following childbirth. are 2 female hormones made mainly by a woman’s ovaries until menopause. After menopause, the ovaries stop making estrogen, but the body continues to make a small amount of estrogen with an enzyme called aromatase.
Estrogen and progesterone can stimulate the growth of some breast cancers. Normal breast cells and some types of breast cancer cells have estrogen and progesterone receptors inside or on their surface. These receptors are where the hormones attach to the cells.
Breast cancer tissue is tested to see if it has receptors for estrogen, progesterone or both. This is referred to as the hormone receptor status. Hormonal therapy is used only in women who have breast cancer that is estrogen receptor positive (ER positive or ER+) and progesterone receptor positive (PR positive or PR+). In about two-thirds of all cases of breast cancer, estrogen and progesterone promote the growth of cancer because the tumour contains receptors for estrogen, progesterone or both.
Hormonal therapy is not used in women who have hormone receptor–negative tumours.
Hormonal therapy may be used:
- after surgery and radiation therapy to stop cancer cells that may have been left behind from growing and to reduce the risk of the cancer recurring (adjuvantadjuvantTreatment given in addition to the first-line therapy (the first or standard treatment) to help reduce the risk of a disease (such as cancer) coming back (recurring). hormonal therapy)
- before surgery, to shrink the primary tumour, especially in older women with breast cancer that is ER+, PR+ or both
- as part of a combined treatment approach for locally advanced breast cancer
- to decrease the chance of cancer developing in the opposite breast
- to treat breast cancer that has recurred
- to relieve pain or to control the symptoms of metastatic breast cancer (palliative therapy)
The type of hormonal therapy used and the doses and schedules of drugs vary from woman to woman.
The choice of hormonal therapy for breast cancer and the length of time it is given will depend on many factors, including:
- whether a woman has reached menopause
- Premenopausal women are given different hormonal therapies than post-menopausal women.
- the stage of breast cancer
- whether a woman has any other health problems (such as osteoporosis or a high risk of blood clots) that may prevent her from taking a certain hormonal therapy
- any hormonal therapies that a woman already received
- disease progression
- If a breast cancer progress after one type of hormonal therapy has been given, doctors may try another type of hormonal therapy.
The following are the most common hormonal therapies used to treat breast cancer:
- aromatase inhibitors
- ovarian ablation
For more detailed information on specific drugs go to sources of drug information.
Anti-estrogen drugs, also called selective estrogen receptor modulators (SERMs), do not affect estrogen levels in the body. They work by stopping breast cancer cells from getting estrogen. Anti-estrogens bind directly to and block the estrogen receptors.
The anti-estrogen drugs used for breast cancer are:
Tamoxifen (Nolvadex, Tamofen) is the most commonly used anti-estrogen drug. It is used in both premenopausal and post-menopausal women. Tamoxifen is given by mouth (orally) as a pill.
When used as an adjuvant therapy for low-risk breast cancer:
- Tamoxifen is usually taken for 5 years after surgery.
- Post-menopausal women may be switched to an aromatase inhibitor (see below) after 2–3 years of taking tamoxifen.
- Premenopausal women may be offered ovarian ablation with luteinizing hormone–releasing hormone (LHRH) agonists (see below) in combination with tamoxifen.
When used for metastatic or recurrent breast cancer, tamoxifen is taken until there is evidence that the cancer is progressing.
Tamoxifen increases the risk of endometrial (uterine) cancer, deep vein thrombosis (DVT), stroke and possibly heart attack. For this reason, it is used with caution in women who have a personal or a strong family history of these conditions.
Fulvestrant (Faslodex) is a drug that reduces the number of estrogen receptors on breast cancer cells. It is given as an injection into the muscles of the buttock.
Fulvestrant is used to treat post-menopausal women with locally advanced or metastatic breast cancer that has progressed after using tamoxifen.
Aromatase is an enzyme involved in the production of estrogen in the body. Aromatase inhibitors are drugs that stop the production or block the actions of aromatase, which in turn lowers the level of estrogen in the body.
Aromatase inhibitors are only used in post-menopausal women because they have much smaller amounts of estrogen in their bodies and blocking aromatase activity is effective in reducing estrogen levels. Aromatase inhibitors do not work in premenopausal women because these drugs have no effect on the ovaries.
Aromatase inhibitors are given by mouth (orally) as a pill. The most common aromatase inhibitors are:
- letrozole (Femara)
- anastrozole (Arimidex)
- exemestane (Aromasin)
All 3 of these aromatase inhibitors may be offered to treat breast cancer. The type of aromatase inhibitor offered will depend on a woman’s situation and other factors.
Aromatase inhibitors may be used:
- after a woman has been on tamoxifen for 2–5 years
- An “early switch” is when a woman is switched to an aromatase inhibitor after she has been on tamoxifen for 2–3 years.
- A “late switch” is when a woman is switched to an aromatase inhibitor after she has completed more than 3 years of tamoxifen therapy or has become post-menopausal after 3 years of tamoxifen therapy. This is also known as “extended adjuvant” therapy.
- The aromatase inhibitor may be taken for 2–3 years after switching from tamoxifen therapy.
- Letrozole may be taken for up to 5 years after switching from tamoxifen therapy.
- after completing tamoxifen therapy
- Recent study results showed that women who began taking letrozole up to 5 years after completing tamoxifen therapy had a reduced risk of their breast cancer returning.
- as the primary hormonal therapy for 5 years, instead of tamoxifen, for women who have breast cancer that is one of the following:
- in women who cannot take tamoxifen because of its side effects
- instead of tamoxifen as the first hormonal therapy in women with breast cancer that has recurred
- When an aromatase inhibitor is used for advanced breast cancer, it is continued until there is evidence that the cancer is progressing.
Ovarian ablation (or ovarian suppression) refers to treatments that stop the ovaries from making estrogen. Reducing the level of estrogen made in the body helps prevent and stop breast cancer cells from growing.
Ovarian ablation is not often used as an adjuvant treatment for breast cancer. At this time, it is not used along with chemotherapy or tamoxifen. Researchers are currently conducting clinical trials for ovarian ablation in combination with tamoxifen or aromatase inhibitors.
Ovarian ablation may be used in premenopausal women:
- if the woman does not wish to have chemotherapy or cannot have other breast cancer treatments because of other medical concerns
- to treat metastatic or recurrent breast cancer
Ovarian ablation can be done in one of 3 ways: surgery, drugs (luteinizing hormone–releasing hormone agonists) or radiation therapy.
Surgery is used to remove the ovaries (oophorectomy), the main source of estrogen in premenopausal women. This method of ovarian ablation may be preferred in older, premenopausal women who no longer wish to have children.
Luteinizing hormone–releasing hormone (LHRH) agonists
Luteinizing hormone–releasing hormone (LHRH) is produced by the hypothalamus. It stimulates the pituitary gland to produce luteinizing hormone (LH), which in turn stimulates the ovaries to produce estrogen.
LHRH agonists are drugs that stimulate the pituitary gland to produce more LHRH. Eventually, the pituitary gland stops responding to the stimulation, which in turn stops the ovaries from producing estrogen. LHRH agonists may be combined with tamoxifen to reduce the amount of estrogen in the body, as well as reduce the number of estrogen receptors on the breast cancer cells.
The most common LHRH agonists used for ovarian ablation are:
- goserelin (Zoladex)
- leuprolide (Lupron, Lupron Depot, Eligard)
- buserelin (Suprefact)
LHRH agonists are given by an injection under the skin. Depending on the drug, injections are given every month or every third month. They are continued either:
- 3–5 years as an adjuvant therapy
- until the breast cancer progresses (in women with metastatic or recurrent breast cancer)
Radiation directed at the ovaries can destroy their ability to produce estrogen. It usually takes about 3 months following radiation therapy for the level of estrogen to decrease. Radiation therapy is rarely used a method of ovarian ablation, though it may be offered to women who cannot have surgery or LHRH agonists.
Progestins are progesterone-like hormonal drugs. Progestins may be used to:
- counteract some of the negative effects of estrogen
- stop estrogen from being made
- compete with progesterone for receptor sites on breast cancer cells
The most common progestin drug used for breast cancer is megestrol (Megace, Apo-megestrol, Nu-megestrol, Lin-megestrol). It is given by mouth (orally) as a pill. The drug is taken until there is evidence that the cancer is progressing.
Progestins are rarely used to treat breast cancer. They may be used in women with metastatic breast cancer that:
- does not respond to other hormonal therapies
- are resistant to tamoxifen
Androgens are male hormones. Androgen drugs are used to block the ability of the pituitary gland to control estrogen production. The most common androgen drug used is fluoxymesterone (Halotestin). It is given by mouth (orally) as a pill. The drug is taken until there is evidence that the cancer is progressing.
Androgens are rarely used as a method of ovarian ablation. It may be used to treat women with:
- metastatic breast cancer that is no longer responding to other hormonal therapies
- recurrent breast cancer
I’m extremely grateful to the Canadian Cancer Society for funding my research with an Innovation Grant.
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