Treatment for metastatic breast cancer (also called stage IV or advanced breast cancer) varies from person to person. Treatment is guided by:
Learn more about factors that affect treatment options.
Tumors often develop resistance (stop responding) to drugs used to treat metastatic breast cancer. So, it is common to change therapies fairly often. You usually start one drug therapy, and are followed to see whether:
Every few months, you will have a physical exam and imaging tests (such as an X-ray or a CT scan) to see if the cancer is responding to the treatment. This is called “restaging.” If the treatment is effective (and you can tolerate the side effects) at the time of restaging, then the treatment is typically continued. If the treatment is no longer effective, then you may be advised to switch to a different drug.
In some cases, blood tests for tumor markers may also be used to help monitor metastatic breast cancer. You may be tested every few months for the tumor markers called cancer antigen 15-3 (CA15-3) or cancer antigen 27.29 (CA27.29) . These tests are similar, so usually one, but not both, of these tests are done. There is no test score that means the tumor has spread (that metastatic breast cancer has worsened). Rather, whether the test score rises or falls for a person may give some information on tumor spread.
Tumor marker tests are not helpful in every case. Some people with rising tumor marker levels do not have tumor growth and some people with tumor growth have normal tumor marker levels.
Health care providers do not make treatment decisions based upon tumor marker testing alone. However, they may combine the information from a tumor marker test with information on your symptoms and findings from imaging tests (such as bone scans). Talk to your provider about whether tumor marker testing is right for you.
Hormone therapy is usually the first treatment for metastatic breast cancers that are hormone receptor-positive. These drugs work by preventing the cancer cells from getting the estrogen they need to grow.
Some hormone therapies, like tamoxifen, attach to the estrogen receptors on the cancer cells and block estrogen from attaching to the receptor. Other therapies, like aromatase inhibitors, lower the level of estrogen in the body so the cancer cells cannot get the estrogen they need.
For women, the choice of hormone therapy depends on menopausal status and any past hormone treatment for early breast cancer .
Some hormone therapy drugs (like tamoxifen and aromatase inhibitors) are given in pill form. Others (like goserelin) are given by injection. Find a list of hormone therapy drugs used to treat metastatic breast cancer and whether they are given in pill form or by injection.
Learn more about hormone therapies.
For premenopausal women, hormone therapy often begins with ovarian suppression. Ovarian suppression lowers hormone levels in the body so the tumor cannot get the estrogen it needs to grow. This may involve surgery to remove the ovaries (oophorectomy) or, more often, drugs (such as goserelin) to stop the ovaries from producing hormones.
Tamoxifen is also used to treat metastatic breast cancer in premenopausal women. However, it may not be an option for women whose cancer progressed during past tamoxifen treatment.
Combining ovarian suppression and tamoxifen may improve survival over either treatment alone [5-6].
Hormone therapy for postmenopausal women can be tamoxifen (or another anti-estrogen drug, such as fulvestrant) or an aromatase inhibitor. If the first hormone therapy stops working and the cancer starts to grow again, a second hormone therapy can be used. If the second drug stops working, another can be tried. At some point—even though it may be years down the line—hormone therapy almost always stops being effective. At this point, chemotherapy may be recommended.
Ovarian suppression is not helpful for postmenopausal women because their ovaries have already stopped producing large amounts of estrogen. (Postmenopausal women still make a small amount of estrogen in fat tissue and the adrenal glands.)
Find a list of hormone therapy drugs commonly used to treat metastatic breast cancer.
mTOR (mammalian target of rapamycin) inhibitors are a class of targeted therapy drugs that may increase the benefit of hormone therapy. The mTOR inhibitor everolimus (Afinitor) is FDA-approved for the treatment of hormone receptor-positive, HER2/neu-negative (HER2-negative) metastatic breast cancers in postmenopausal women who have been treated with the aromatase inhibitor letrozole or anastrozole. Studies have shown the combination of everolimus and the aromatase inhibitor exemestane can slow the growth of such cancers better than exemestane alone [7-8]. Everolimus is given in pill form.
Side effects of everolimus include mouth ulcers, infections, rash, fatigue, diarrhea, decreased appetite and in rare cases, lung problems [7-8].
CDK4 and CDK6 are enzymes important in cell division. CDK4/6 inhibitors are a new class of drugs designed to interrupt the growth of cancer cells. The CDK4/6 inhibitor palbociclib (Ibrance) in combination with hormone therapy is FDA-approved for the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer. Study findings have shown that palbociclib in combination with the aromatase inhibitor letrozole can increase the time before cancer spreads better than letrozole alone . Palbociclib is given in pill form.
Other CDK4/6 inhibitors are under study for use in metastatic breast cancer treatment .
The more common side effects of palbociclib include low white blood cell counts, low red blood cell counts (anemia), fatigue, nausea, mouth sores, hair thinning, diarrhea and in rare cases, blood clots [49-50].
Chemotherapy is a first treatment for people with hormone receptor-negative tumors and those who have life-threatening metastases. It is also used to treat cancers that no longer respond to hormone therapy. One benefit of chemotherapy is response time. Chemotherapy can shrink tumors faster than hormone therapy.
As with hormone therapies, if the first chemotherapy drug (or combination of drugs) stops working and the cancer begins to grow again, a second or third drug can be used. With each new drug, though, it is less likely the cancer will shrink. And, if the cancer does shrink, it often does so for a shorter period of time with each new drug. It is not uncommon for people to have multiple chemotherapy regimens (often four or more) over the course of treatment for metastatic breast cancer.
Learn more about chemotherapy.
Find a list of chemotherapy drugs commonly used to treat metastatic breast cancer.
About 15 to 20 percent of breast cancers have high amounts of a protein called HER2/neu on the surface of the cancer cells (called HER2/neu-positive (HER2-positive) breast cancer) [9-10]. The HER2/neu protein is important for cancer cell growth.
HER2/neu status is determined by testing the tumor tissue.
Learn more about HER2/neu status.
Trastuzumab (Herceptin) is a specially made antibody that targets HER2-positive cancer cells. When attached to the HER2/neu protein, trastuzumab slows or stops the growth of these cells. Trastuzumab is only used to treat HER2-positive breast cancers. It is given through an IV (intravenously).
Clinical trials in women with HER2-positive metastatic breast cancer have shown that trastuzumab can shrink tumors and slow cancer growth when used alone or combined with chemotherapy [11-15]. Trastuzumab is used as a first treatment for HER2-positive metastatic breast cancer as well as a treatment for HER2-positive metastatic cancer that has started to progress with chemotherapy [11-15].
In some cases, HER2-positive tumors may spread to the brain. Because trastuzumab is not able to cross the blood-brain barrier, it is not used to treat brain metastases.
Trastuzumab has fewer side effects than chemotherapy. It does not cause hair loss, nausea or vomiting, and has no effect on bone marrow.
In rare cases, deaths due to heart or lung problems have been linked to the use of trastuzumab [4,11]. Although the chance of such an event is small, discuss this risk with your health care provider before starting treatment. Your heart will be checked before and during treatment to help ensure there are no problems.
For a summary of research studies on the use of trastuzumab in treating metastatic breast cancer, visit Breast Cancer Research.
Pertuzumab (Perjeta) is an antibody that targets HER2-positive cancer cells in a different way than trastuzumab. Pertuzumab is FDA-approved for the treatment of HER2-positive metastatic breast cancers that have not been treated with chemotherapy, trastuzumab or lapatinib. It is given through an IV.
Findings from a randomized controlled trial showed that pertuzumab in combination with trastuzumab and chemotherapy slowed the growth of HER2-positive metastatic breast cancer and increased survival better than trastuzumab and chemotherapy alone [14,27].
Possible side effects of pertuzumab include diarrhea, rash, mouth sores, low white blood cell count and dry skin .
Trastuzumab emtansine (T-DM1, Kadcyla) is a new type of targeted therapy for HER2-positive metastatic breast cancer. T-DM1 consists of trastuzumab and a chemotherapy called DM1. Combining these drugs allows the targeted delivery of chemotherapy to HER2-positive cancer cells. T-DM1 is given through an IV.
Findings from a randomized controlled trial showed T-DM1 increased overall survival better than lapatinib plus the chemotherapy drug capecitabine for women with metastatic HER2-positive breast cancers . T-DM1 is FDA-approved for the treatment of HER2-positive metastatic breast cancers that have progressed on trastuzumab and a taxane-based chemotherapy.
Possible side effects of T-DM1 include nausea, fatigue, muscle and joint pain, low white blood cell count, headache and constipation. It can also cause severe liver and heart problems. It does not cause hair loss .
Tyrosine-kinase inhibitors, such as lapatinib (Tykerb), are a class of drugs that target enzymes important for cell functions (called tyrosine-kinase enzymes). These drugs can block tyrosine-kinase enzymes at many points along the cancer growth pathway.
Lapatinib is FDA-approved for the treatment of HER2-positive metastatic breast cancer in women who have already had chemotherapy and trastuzumab. Lapatinib is taken in pill form.
Lapatinib combined with chemotherapy can increase time to cancer spread and improved overall survival compared to chemotherapy alone in women with HER2-positive metastatic breast cancer [18-19].
Some studies have shown lapatinib combined with the aromatase inhibitor letrozole may increase time to cancer spread compared to the use of letrozole alone in women with hormone receptor-positive, HER2-positive metastatic breast cancer [20-21].
One clinical trial found lapatinib combined with trastuzumab may increase time to cancer spread compared to the use of trastuzumab alone in women with HER2-positive metastatic breast cancer .
Early findings show lapatinib holds promise for HER2-positive metastatic cancer with brain metastases as it can pass through the blood-brain barrier [22-24]. Most therapies, including trastuzumab, cannot cross the blood-brain barrier. In rare cases, lapatinib can help shrink or slow the growth of brain metastases [22-24].
Side effects of lapatinib include diarrhea, nausea, vomiting, rash and fatigue. In rare cases, it has been linked to liver and lung problems [15,18-21].
*Please note, the information provided within Komen Perspectives articles is only current as of the date of posting. Therefore, some information may be out of date at this time.
Breast Cancer 101 - Treatment for Stage IV
Questions to Ask Your Doctor About Metastatic Breast Cancer
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