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If you have metastatic breast cancer that is hormone receptor-positive, hormonal therapy will be part of your treatment plan.
For HR-positive metastatic breast cancer, many medications will generally be used first before chemotherapy. These medications are called “hormonal drugs” and include fulvestrant and aromatase inhibitors. Treatment decisions are made based on previous treatment and tumor features.
This article focuses on the different hormonal drugs in metastatic breast cancer and the factors that will be taken into account in choosing your treatment.
What is Metastatic Breast Cancer?
Before we talk about hormonal drugs used to treat metastatic breast cancer, let’s define some terms.
Metastatic breast cancer is also called advanced breast cancer. If you are diagnosed with breast cancer that has spread to other parts of the body at the same time you are diagnosed with breast cancer in your breast, you have Stage IV cancer.
- Metastatic breast cancer is cancer that has left the breast and nearby lymph nodes and spread to other parts of the body.
- The cells in other parts of the body are still breast cancer. What this means is that the cancer cells will be treated with medicine specific for breast cancer.
- Common places that breast cancer can spread are the bones, lung, or liver.
It is important to note that, while a person may have metastatic breast cancer now, they may have been diagnosed with another form of breast cancer in the past (for example, Stage II or III).
Hormones and Hormone Receptors in Breast Cancer
Most people with breast cancer have cancer that grows in response to certain hormones.
The hormone receptors on the breast cancer reflect the cancer cell’s own biology. That is, whether or not the tumor has hormone receptors is not related to your own estrogen levels.
The two main hormones that affect breast cancer are estrogen and progesterone. Estrogen and progesterone are made in the ovaries and in the adrenal glands. Even people with no ovarian function and people who used to have ovarian function have estrogen in their bodies.
A receptor is a protein found inside or on the surface of a cell. Hormones bind to hormone receptors on cells throughout your body. Breast cancer cells are described as having estrogen receptors, progesterone receptors, both, or neither.
Estrogen and progesterone attach to cancer cells that have estrogen and progesterone receptors. When the hormones attach to the cancer cells, they aid cancer cell growth. This is why hormonal therapy as cancer treatment focuses on estrogen and progesterone.
Hormonal therapy lowers the amount of estrogen that reaches the cancer cells. It does this by affecting the estrogen receptor or by lowering estrogen in the body.
Hormonal therapy is also called endocrine therapy because hormones are made by your body’s endocrine system.
Some breast cancer cells have hormone receptors specifically for estrogen or progesterone.
- The secreting cell is the cell that makes the hormone, such as the ovaries, adrenal glands, and testes.
- The blue dot is the hormone that is made in the cell, such as estrogen or progesterone.
- The target cell is a breast cancer cell.
- The green block on top of the target cell is the hormone receptor where the estrogen or progesterone binds.
Hormone receptor-positive (HR+) breast cancer cells have estrogen hormone receptors, progesterone hormone receptors, or both. Most breast cancer cells are HR+.
Estrogen receptor-positive (ER+) cells are cells that appear to respond to estrogen and may stop growing or die when estrogen is blocked from cancer treatment.
Progesterone receptor-positive (PR+) cells are cells that appear to respond to progesterone to grow and may stop growing or die when progesterone is blocked from cancer treatment.
Breast cancer cells usually but not always, have both types of hormone receptors.
Hormonal Therapy
Hormonal therapy treats cancer by targeting the hormones produced in your body. The two main hormones that we look at for metastatic breast cancer treatment are progesterone and estrogen. Hormone receptor-positive breast cancer will have estrogen receptor, progesterone receptor, or both. Hormonal therapy is also called endocrine therapy because hormones are made in the body’s endocrine system.
The main types of hormonal therapy are treatments that involve suppression or removal of the ovaries, aromatase inhibitors, and anti-estrogen therapy.
Ovarian Suppression
Ovarian suppression is stopping the ovaries from making hormones. This can be permanent or temporary.
This can be done permanently by a procedure called an oophorectomy, in which your ovaries are surgically removed. Another option to permanently stop the ovaries from working is using radiation therapy given only to the ovaries.
Other forms of ovarian suppression are temporary. They use drugs to “shut down” the ovaries and cause menopause for women who have not reached menopause yet. Another name for this is “medical menopause.” Since this is done with drugs, this may be reversed when treatment is over. The two main drugs used for medical menopause are goserelin and leuprolide. These drugs are also used in male metastatic breast cancer.
- Goserelin (Zoladex), which is given as a monthly injection
- Leuprolide (Eligard or Lupron Depot)which is given as a monthly injection (This can also be given every three months as long as it is clear that every three months is working in you.)
Because these treatments are like going through menopause, you may have hot flashes, night sweats, muscle and joint discomfort, decreased sex drive, and vaginal dryness. Other less common side effects are headaches, swelling of your hands or feet, headaches, mood changes, and sleeping troubles.
Let your doctor know if you are experiencing any side effects. Helping you get through ovarian suppression or removal will improve your quality of life.
Aromatase Inhibitors
Aromatase inhibitors are medications that help decrease the formation of estrogen in your body. They are discussed below in the Hormonal Drugs for Metastatic Breast Cancer section below.
Anti-Estrogens
Anti-estrogen drugs block the effects of estrogen in breast tissue. There are two groups: selective estrogen receptor modifiers and selective estrogen receptor down-regulators. Both of these groups act in slightly different ways. But ultimately they block the effects of estrogen on your breast tissue. These are discussed below in the Hormonal Drugs for Metastatic Breast Cancer section below.
Hormonal Drugs for Metastatic Breast Cancer
Anti-Estrogens
Anti-estrogens block the effects of estrogen in breast tissue, therefore preventing the cancer cells from growing. Examples are listed below:
- Tamoxifen
- Toremifene (Fareston)
- Fulvestrant (Faslodex)
Tamoxifen and toremifene are given as a tablet and taken by mouth. These can be taken with or without food.
Both of these medications can cause your hot flashes, cold sweats, vaginal dryness, discharge or bleeding, muscle pain, stiffness or pain in your joints, or nausea.
Tell your doctor if you are experiencing any side effects from any medication.
Fulvestrant is commonly used in metastatic breast cancer. You may refer to it by its brand name Faslodex. It is given as two 1-2 minute injections into your muscle, usually in the buttocks.
First, one buttock will receive a 250 mg injection that will take about 1-2 minutes to receive. Then, the second buttock will receive a 250 mg injection that will take about 1-2 minutes to receive.
The total between both buttocks will be 500 mg of fulvestrant. This is one complete “dose” of the medication. Each dose will be given at your doctor’s office.
Here is an example calendar of what your fulvestrant dosing schedule or timeline may look like:
The first three fulvestrant doses are separated 2 weeks apart.
After completing the third dose, your fourth dose will be 4 weeks later. Every dose after this will continue to be 4 weeks apart.
Some side effects you may experience from this drug are tiredness, headache, joint pain, hot flashes, and tummy issues like diarrhea, nausea, stomach pain, constipation, and reduced appetite.
Aromatase Inhibitors
Aromatase inhibitors stop the formation of estrogen in your body. This prevents the cancer cells from growing because the estrogen that they use won’t be formed.
There are three aromatase inhibitors. They are all equally effective. The generic forms are as good as the brand name versions.
- Anastrozole (brand name: Arimidex)
- Letrozole (brand name: Femara)
- Exemestane (brand name: Aromasin)
All of these medications are given as a tablet that is taken by mouth.
Side effects include bone pain, joint pain, vaginal dryness, hot flashes and, rarely, shortness of breath.
Tell your medical team if you are experiencing any side effects. Managing your side effects is an important part of improving your quality of life.
Hormones
Hormones are used in certain circumstances to treat metastatic breast cancer. Although the way in which they work is not clearly known, your cancer may respond to these drugs. The hormone drugs that are used are listed below. All of these medications are given as a tablet and taken by mouth.
- Megestrol (Megace)
Some side effects you may experience from this medication are an upset stomach, throwing up, diarrhea, gas, sleeping trouble, hot flashes, feeling more hungry, and a lot of sweating. Most people also gain weight, so this medication may help if you are losing weight.
- Fluoxymesterone (Androxy)
A few side effects are headaches, pimples, and facial hair. This medication can also cause enlarged breasts in males.
- Estradiol (Estrace Oral)
Estradiol may cause headache, dizziness, upset stomach, throwing up, constipation, stomach pain, bloating, tender or enlarged breasts, vaginal bleeding or spotting, joint pain, or leg cramps.
Tell your doctor if you are experiencing any side effects from any medication. As with the other medications, side effect management is key in terms of improving your quality of life.
How Do Your Doctors Decide Which Medication You Will Get?
Treatment decisions are made based on several factors. A few of these are previous hormonal treatment you have had, whether or not the cancer cells have the HER2 protein, medication side effects, and whether or not you have ovaries that still make estrogen.
HER2 is a protein that stands for Human Epidermal Growth Factor Receptor-2. If cancer cells have this protein, they are described as being HER2-positive, or HER2(+). If cancer cells do not have this protein, they are described as being HER2-negative, or HER2(-). When someone refers to your cancer’s HER2 status, they are asking if it is positive or negative.
Hormonal therapy is used only if the cancer is hormone receptor-positive, or HR(+). If your cancer does not have hormone receptors, hormonal therapy will not be part of your treatment plan. The specific treatment options (a combination of drugs) are chosen based on whether the HER2 receptor is positive or negative.
Here are a few examples of what your treatment may look like if you have hormone receptor-positive metastatic breast cancer.
Notice the different options available if your tumor status is HER2-positive or HER2-negative.
People With Ovarian Function
If you still have functioning ovaries, meaning blood work shows your ovaries are still working (and some people may still have their monthly period), you will most likely receive ovarian suppression.
This is done to shut off the estrogen produced by ovaries. Metastatic breast cancer can respond to having the ovaries suppressed or removed. People with ovarian function are given therapy to cause menopause (ovarian suppression) along with the other hormonal treatments mentioned above.
Male Breast Cancer
Testosterone is converted to estrogen in the body, so hormonal therapy is used in men as well. Treating men with metastatic breast cancer is similar to treating women. The medications and regimens are the exact same. For example, if a man is on anastrozole (an aromatase inhibitor).
Contraception
Hormonal therapy can cause serious birth defects. It is important to use contraception to avoid getting pregnant during treatment.
As described above, most breast cancer cells have the estrogen and progesterone receptors. Birth control pills and other hormonal birth control have similar hormones in them (estrogen and progesterone) because they are used to copy your body’s natural menstrual cycle.
Hormonal birth control can also increase the risk of blood clots. Advanced cancer is also a risk factor for blood clots.
We recommend that people with breast cancer not use hormonal forms of contraception. Below are examples of hormonal birth control options that should be avoided in people with breast cancer:
- Birth control pills
- Birth control patches
- Estrogen rings
- Estrogen implants
- Progesterone IUDs
Speak with your medical team about your options for birth control before starting treatment.
For people with metastatic breast cancer, condoms are a good option. Copper IUDs and diaphragms with spermicide can be used as well because they do not have hormones in them.
For male metastatic breast cancer, cancer and cancer medications can damage sperm. Use birth control, like condoms, to avoid pregnancy.
Summing It Up…
Hormone therapy is used only in people with metastatic breast cancer that is hormone receptor (HR)-positive. People who have functioning ovaries will be offered removal of the ovaries, radiation therapy to the ovaries, or injections to shut down the ovaries.
From there, the treatment depends on if the cancer is HER2(+) or HER2(-). Treatment is similar in for male and female breast cancer.
If you experience any side effects, speak with your medical team. Side effect management will help you have the best quality of life.
Use birth control to prevent birth defects from therapy.
References
- National Cancer Institute Dictionary of Cancer Terms. cancer.gov. https://www.cancer.gov/publications/dictionaries/cancer-terms. Published February 2, 2011. Accessed September 29, 2020.
- Gradishar WJ, Anderson BO, Abraham J, et al. National Comprehensive Cancer Network Guidelines Breast Cancer. Version 5.2020 From the National Comprehensive Cancer Network; July 2020. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed September 29, 2020.
- National Comprehensive Cancer Network (US). NCCN Guidelines for Patients: Breast Cancer – Metastatic. Version 2020. Fort Washington, PA: NCCN; 2020.
- Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2016. Available from: http://online.lexi.com. Subscription required to view.
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