Some types of breast cancer are affected by hormones in the blood. ER-positive and PR-positive breast cancer cells have receptors that attach to estrogen, which helps them grow. There are several drugs that use different ways to stop estrogen from attaching to the receptors.
Hormone therapy is a form of systemic therapy, meaning it reaches cancer cells anywhere in the body and not just in the breast. It is recommended for women with hormone receptor-positive (ER-positive and/or PR-positive) breast cancers, but it does not help women whose tumors are hormone receptor-negative (both ER- and PR-negative).
When might hormone therapy be used?
Hormone therapy is most often used after surgery (as adjuvant therapy) to help reduce the risk of the cancer coming back, but it can be started before surgery (as neoadjuvant treatment) as well. It is usually used for at least 5 years.
Hormone therapy can also be used to treat cancer that has come back after treatment or that has spread to other parts of the body.
How does hormone therapy work?
About 2 out of 3 breast cancers are hormone receptor-positive. Their cells have receptors that attach to the hormones estrogen (ER-positive cancers) and/or progesterone (PR-positive cancers). For these cancers, high estrogen levels help the cancer cells grow and spread.
There are several different types of hormone therapy that use different ways to keep estrogen from helping the cancer grow. Most types of hormone therapy for breast cancer either lower estrogen levels or stop estrogen from acting on breast cancer cells.
Drugs that block estrogen
These drugs work by stopping estrogen from affecting breast cancer cells.
Tamoxifen and Toremifene (Fareston®)
These drugs block estrogen receptors in breast cancer cells. This stops estrogen from binding to the cancer cells and telling them to grow and divide. While tamoxifen and toremifene act like an anti-estrogen in breast cells, they act like an estrogen in other tissues, like the uterus and the bones. Because these drugs act like estrogen in some tissues but like anti-estrogens in others, they are called selective estrogen receptor modulators (SERMs).
Tamoxifen is the most common SERM. It can be used in several ways:
- For women with hormone receptor-positive breast cancer treated with surgery, tamoxifen can help lower the chances of the cancer coming back and raise the chances of living longer. It can also lower the risk of getting a new cancer in the other breast. Tamoxifen can be started either after surgery (adjuvant therapy) or before surgery (neoadjuvant therapy) and is usually taken for 5 to 10 years. For early stage breast cancer, this drug is mainly used for women who have not yet gone through menopause. (If you have gone through menopause, aromatase inhibitors are usually used instead.)
- For women who have been treated for ductal carcinoma in situ (DCIS) that is hormone receptor-positive, taking tamoxifen for 5 years lowers the chance of the DCIS coming back. It also lowers the chance of getting an invasive breast cancer.
- For women with hormone-positive breast cancer that has spread to other parts of the body, tamoxifen can often help slow or stop the growth of the cancer, and might even shrink some tumors.
- In women at high risk of breast cancer, tamoxifen can be used to help lower the risk of developing breast cancer.
Toremifene works in a similar way, but is only approved to treat metastatic breast cancer. It is not likely to work if tamoxifen has already been used and has stopped working.
These drugs are taken by mouth, most often as a pill.
The most common side effects of tamoxifen and toremifene are:
- Hot flashes
- Vaginal dryness or discharge
- Mood swings
Some women with cancer spread to the bones may have a "tumor flare" with pain and swelling in the muscles and bones. This usually subsides quickly, but in some rare cases a woman may also develop a high calcium level in the blood that is hard to control. If this happens, the treatment may need to be stopped for a time.
Rare, but more serious side effects are also possible:
- These drugs can increase the risk of developing cancers of the uterus (endometrial cancer and uterine sarcoma) in women who have gone through menopause. Tell your doctor right away about any unusual vaginal bleeding (a common symptom of both of these cancers). Most uterine bleeding is not from cancer, but this symptom always needs prompt attention.
- Blood clots are another possible serious side effect. They usually form in the legs (called deep vein thrombosis or DVT), but sometimes a piece of clot may break off and end up blocking an artery in the lungs (pulmonary embolism or PE). Call your doctor or nurse right away if you develop pain, redness, or swelling in your lower leg (calf), shortness of breath, or chest pain, because these can be symptoms of a DVT or PE.
- Rarely, tamoxifen has been associated with strokes in post-menopausal women, so tell your doctor if you have severe headaches, confusion, or trouble speaking or moving.
- These drugs might also increase the risk of a heart attack.
Depending on a woman's menopausal status, tamoxifen can have different effects on the bones. In pre-menopausal women, tamoxifen can cause some bone thinning, but in post-menopausal women it is often good for bone strength.
The benefits of taking these drugs outweigh the risks for almost all women with hormone receptor-positive breast cancer.
Fulvestrant is a drug that blocks the estrogen receptor and then also eliminates it temporarily. This drug is not a SERM – it acts like an anti-estrogen throughout the body.
Fulvestrant is used to treat metastatic breast cancer, most often after other hormone drugs (like tamoxifen and often an aromatase inhibitor) have stopped working.
It is given by injections into the buttocks. For the first month, the shots are given 2 weeks apart. After that, they are given once a month.
Common short-term side effects can include:
- Hot flashes
- Night sweats
- Mild nausea
Because fulvestrant blocks estrogen, in theory it could cause weakened bones (osteoporosis) if it is taken for a long time.
Fulvestrant is currently approved only for use in post-menopausal women. It is sometimes used “off-label” in pre-menopausal women, often combined with a luteinizing-hormone releasing hormone (LHRH) agonist to turn off the ovaries (see the section on ovarian ablation below).
Treatments to lower estrogen levels
Some hormone treatments work by lowering the estrogen levels in the body. Because estrogen encourages hormone receptor-positive breast cancers to grow, lowering the estrogen level can help slow the cancer’s growth or help prevent it from coming back.
Aromatase inhibitors (AIs)
Aromatase inhibitors (AIs) are drugs that stop estrogen production in post-menopausal women. They are not helpful before menopause, when most estrogen is made by the ovaries. But for women whose ovaries aren’t working, either due to menopause or certain treatments, a small amount of estrogen is still made by an enzyme (called aromatase) in the fat tissue. AIs work by blocking aromatase from making estrogen.
There are three AIs that all seem to work about equally well in treating breast cancer:
- Letrozole (Femara)
- Anastrozole (Arimidex)
- Exemestane (Aromasin)
These drugs are taken daily as pills.
Several studies have compared AIs to tamoxifen as adjuvant (after surgery) hormone therapy in post-menopausal women. Taking these drugs, either alone or after tamoxifen, has been shown to work better than taking just tamoxifen for 5 years to reduce the risk of the cancer coming back later.
Schedules that are known to be helpful include:
- Tamoxifen for 2 to 3 years, followed by an AI to complete 5 years of treatment
- Tamoxifen for 5 years, followed by an AI for 5 years
- An AI for 5 years
For most post-menopausal women whose cancers are hormone receptor-positive, most doctors recommend taking an AI at some point during adjuvant therapy. Right now, standard treatment is to take these drugs for about 5 years (or alternate with tamoxifen for a total of at least 5 years). Studies are now being done to see if taking an AI for more than 5 years would be more helpful.
If you have early-stage breast cancer and had not gone through menopause when you were first diagnosed, your doctor might recommend taking tamoxifen first, and then taking an AI later if you go through menopause during treatment. Another option is taking a drug called a luteinizing hormone-releasing hormone (LHRH) analog, which turns off the ovaries, along with an AI.
The AIs tend to have fewer serious side effects than tamoxifen. They don't cause uterine cancers and very rarely cause blood clots. They can, however, cause muscle pain and joint stiffness and/or pain. The joint pain may be similar to a feeling of having arthritis in many different joints at one time. This side effect may improve by switching to a different AI, but it has led some women to stop treatment. If this happens, most doctors recommend using tamoxifen to complete 5 years of hormone treatment.
Because AIs remove all estrogens from women after menopause, they also cause bone thinning, sometimes leading to osteoporosis and even fractures. If you are taking an AI, you may also be given medicine to strengthen your bones, such as bisphosphonates or denosumab.
For pre-menopausal women, removing or shutting down the ovaries (ovarian ablation), which are the main source of estrogens, effectively makes them post-menopausal. This may allow some other hormone therapies, such as AIs, to work better. Ovarian ablation is most often done to treat metastatic breast cancer, but it is also being studied in women with early-stage disease.
There are several ways to remove or shut down the ovaries:
- Oophorectomy: Surgery is done to remove the ovaries. This is a form of permanent ovarian ablation.
- Luteinizing hormone-releasing hormone (LHRH) analogs: These drugs are used more often than oophorectomy. They stop the signal that the body sends to ovaries to make estrogen, which causes temporary menopause. Common LHRH drugs include goserelin (Zoladex®) and leuprolide (Lupron®). They can be used alone or with other hormone drugs (tamoxifen, aromatase inhibitors, fulvestrant) as hormone therapy in pre-menopausal women.
- Chemotherapy drugs: Some chemo drugs can damage the ovaries of pre-menopausal women so they no longer make estrogen. For some women, ovarian function returns months or years later, but in others, the damage to the ovaries is permanent and leads to menopause. This side effect can sometimes be a helpful (if unintended) consequence of chemotherapy with regard to breast cancer treatment.
All of these methods can cause symptoms of menopause, including hot flashes, night sweats, vaginal dryness, and mood swings.
Less common types of hormone therapy
Some other types of hormone therapy were used more often in the past, but are rarely given now. These include:
- Megestrol acetate (Megace®), a progesterone-like drug
- Androgens (male hormones)
- High doses of estrogen
These might be an option if other forms of hormone therapy are no longer working, but they can often cause side effects.
Last Revised: 05/04/2016