HER2-Targeted Therapies for Metastatic Breast Cancer
Watch our March 2023 MBC Impact Series, New Developments in Treating HER2+ Metastatic Breast Cancer.
HER2-positive breast cancer
The HER2 protein is an important driver of cell growth and survival. HER2-positive breast cancers have high amounts of HER2 protein on the surface of the cancer cells. You may also hear the term HER2 over-expression.
A pathologist determines HER2 status by testing a sample of the metastatic tumor (from a biopsy of the metastases).
Immunohistochemistry (IHC) is a test which detects the amount of HER2 protein on the surface of the cancer cells. The results of an IHC test are used to show HER2 status. An IHC score of 3+ shows a metastatic breast tumor is HER2 positive.
About 10% to 20% of breast cancers are HER2-positive [28-29].
HER2-targeted therapies are used to treat HER2-positive breast cancers.
Learn about HER2-targeted therapies for early breast cancer treatment.
HER2-targeted therapies for metastatic breast cancer treatment
HER2-targeted therapies for HER2-positive metastatic breast cancers | ||
Drug name |
Brand name(s) |
Pill, injection under the skin, or IV drug (given through an IV into a vein)? |
Herceptin (IV drug) and Herceptin Hylecta (injection) |
IV drug or injection |
|
Perjeta (IV drug) and Phesgo (injection combined with trastuzumab) |
IV drug or when combined with trastuzumab, injection |
|
Margenza |
IV drug |
|
Kadcyla |
IV drug |
|
Enhertu |
IV drug |
|
Tukysa |
Pill |
|
Nerlynx |
Pill |
|
Tykerb |
Pill |
|
The National Comprehensive Cancer Network (NCCN) has a video on how some of these HER2-targeted therapies work.
Monitoring metastatic breast cancer
You’ll be monitored (checked) regularly with scans to see if the cancer is responding to treatment. If the treatment is no longer working, or you’re having a lot of side effects, your health care provider will change your treatment or discuss other options.
Learn more about how metastatic breast cancer is monitored.
Trastuzumab (Herceptin) for metastatic breast cancer treatment
Trastuzumab (Herceptin) is a specially-made antibody that targets HER2-positive cancer cells.
Trastuzumab attaches to the HER2 protein on the surface of HER2-positive breast cancer cells. This can slow or stop their growth.
Trastuzumab is only used to treat HER2-positive breast cancers.
It can shrink tumors and slow the growth of HER2-positive metastatic breast cancers when used alone or combined with chemotherapy [30-32].
| For a summary of research studies on trastuzumab and treatment of metastatic breast cancer, visit the Breast Cancer Research Studies section. |
Learn more about treatment for metastatic breast cancer.
Learn about emerging areas in treatment for metastatic breast cancer.
Learn about trastuzumab and treatment for early breast cancer.
How is trastuzumab given?
Trastuzumab is given through an IV into a vein or by an injection under the skin.
Side effects of trastuzumab
Before you begin treatment with trastuzumab, talk with your health care provider about possible side effects and how to manage them.
|
Side Effects |
Trastuzumab |
Possible side effects include headache, fever and chills. Trastuzumab can cause serious heart problems. Your heart will be checked before and during treatment to help make sure there are no problems. |
Adapted from select sources [4,30]. |
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Trastuzumab doesn’t cause hair loss, nausea or vomiting, and has no effect on bone marrow.
Biosimilar trastuzumab
A biosimilar drug is a “generic-like” version of a drug that contains biological products (biologics) such as antibodies or proteins. Trastuzumab is a biologic drug.
There are several FDA-approved biosimilar forms of trastuzumab. To get FDA approval, biosimilars must pass strict testing requirements. FDA-approved biosimilars are safe and effective treatments for HER2-positive early and metastatic breast cancers.
Learn more about biosimilars.
Pertuzumab (Perjeta) for metastatic breast cancer treatment
Pertuzumab (Perjeta) is a specially-made antibody that targets HER2-positive cancer cells, but in a different way than trastuzumab.
Pertuzumab is always given with trastuzumab. Pertuzumab in combination with trastuzumab is FDA-approved as a first treatment for HER2-positive metastatic breast cancers.
Study findings have shown pertuzumab plus trastuzumab and chemotherapy can slow the growth of HER2-positive metastatic breast cancer and increase survival better than trastuzumab and chemotherapy alone [33-34].
| For a summary of research studies on pertuzumab and treatment of metastatic breast cancer, visit the Breast Cancer Research Studies section. |
Learn more about treatment for metastatic breast cancer.
Learn about emerging areas in treatment for metastatic breast cancer.
Learn about pertuzumab and treatment for early breast cancer.
How is pertuzumab given?
Pertuzumab comes in two forms. It can be given:
- Through an IV into a vein
- By injection under the skin when combined with trastuzumab (one injection contains both drugs)
Side effects of pertuzumab
Before you begin treatment with pertuzumab, talk with your health care provider about possible side effects and how to manage them.
|
Side Effects |
Pertuzumab |
Possible side effects include diarrhea, nausea, fatigue and rash. Pertuzumab is always given in combination with trastuzumab. Trastuzumab can cause serious heart problems. Your heart will be checked before and during treatment with pertuzumab and trastuzumab to help make sure there are no problems. |
Adapted from select sources [33-34]. | |
Margetuximab (Margenza) for metastatic breast cancer treatment
Margetuximab (Margenza) is a specially-made antibody that targets HER2-positive cancer cells in a similar way to trastuzumab, but different from pertuzumab.
Margetuximab is FDA-approved for the treatment of HER2-positive metastatic breast cancers that have already been treated with 2 or more HER2-targeted therapies (at least one in the metastatic setting).
Study findings have shown margetuximab in combination with chemotherapy can give people with HER2-positive metastatic breast cancer more time before the cancer worsens compared to trastuzumab in combination with chemotherapy [35].
Learn more about treatment for metastatic breast cancer.
Learn about emerging areas in treatment for metastatic breast cancer.
How is margetuximab given?
Margetuximab is given through an IV into a vein.
Side effects of margetuximab
Before you begin treatment with margetuximab, talk with your health care provider about possible side effects and how to manage them.
|
Side Effects |
Margetuximab |
Possible side effects include fatigue, headache, fever and chills. Margetuximab can cause some heart problems. Your heart will be checked before and during treatment to help make sure there are no problems. |
Adapted from select sources [35-36]. |
|
Ado-trastuzumab emtansine (Kadcyla, T-DM1, trastuzumab emtansine) for metastatic breast cancer treatment
Ado-trastuzumab emtansine (Kadcyla, T-DM1, trastuzumab emtansine) is a HER2 antibody-drug conjugate. It consists of trastuzumab and a chemotherapy drug called DM1 (so it’s sometimes called T-DM1).
Combining trastuzumab and DM1 allows the targeted delivery of the chemotherapy to HER2-positive cancer cells.
Ado-trastuzumab emtansine is FDA-approved for the treatment of HER2-positive metastatic breast cancers that have progressed on trastuzumab and a taxane-based chemotherapy.
Study findings have shown ado-trastuzumab emtansine can increase overall survival better than lapatinib plus the chemotherapy drug capecitabine for women with HER2-positive metastatic breast cancers [37].
Learn more about treatment for metastatic breast cancer.
Learn about emerging areas in treatment for metastatic breast cancer.
Learn about ado-trastuzumab emtansine and treatment for early breast cancer.
How is ado-trastuzumab emtansine given?
Ado-trastuzumab emtansine is given through an IV into a vein.
Side effects of ado-trastuzumab emtansine
Before you begin treatment with ado-trastuzumab emtansine, talk with your health care provider about possible side effects and how to manage them.
|
Side Effects |
Ado-trastuzumab emtansine |
Possible side effects include nausea, fatigue, muscle and joint pain, neuropathy, low platelet counts and headache. Ado-trastuzumab emtansine can also cause liver problems. Your liver will be checked before and during treatment to help make sure there are no problems. Because ado-trastuzumab emtansine contains trastuzumab, it can cause serious heart problems. Discuss this risk with your health care provider before starting treatment. Your heart will be checked before and during treatment to help make sure there are no problems. |
Adapted from select sources [4,38]. | |
Ado-trastuzumab emtansine doesn’t usually cause hair loss.
Trastuzumab deruxtecan (Enhertu, fam-trastuzumab deruxtecan)
Read our blog, Practice-changing Research Results Announced at the 2022 ASCO Annual Meeting.
Trastuzumab deruxtecan (Enhertu, fam-trastuzumab deruxtecan) is a HER2 antibody-drug conjugate. It consists of trastuzumab and the chemotherapy drug deruxtecan.
Combining these drugs allows the targeted delivery of the chemotherapy to HER2-positive cancer cells.
Trastuzumab deruxtecan is FDA-approved for the treatment of HER2-positive metastatic breast cancers that have progressed on at least one past HER2-targeted therapy for metastatic breast cancer.
Study findings show trastuzumab deruxtecan may help shrink tumors in some women with HER2-positive metastatic breast cancers [39].
Study findings also show that trastuzumab deruxtecan can increase overall survival in people with metastatic breast cancer better than ado-trastuzumab emtansine (Kadcyla, T-DM1) [40].
Further, some study findings show trastuzumab deruxtecan can be effective in treating some metastatic breast cancers that have spread to the brain [41].
Trastuzumab deruxtecan and HER2-low metastatic breast cancer
Trastuzumab deruxtecan is also FDA-approved for the treatment of some metastatic breast cancers that have low, but detectable levels of HER2 expression. These are called HER2-low breast cancers.
Immunohistochemistry (IHC) is a test which detects the amount of HER2 protein on the surface of the cancer cells. The results of an IHC test are used to show HER2 status. An IHC score of 1+ or 2+ shows a metastatic breast tumor is HER2-low.
Trastuzumab deruxtecan is used to treat HER2-low metastatic breast cancers that have progressed on past chemotherapy for metastatic breast cancer. It can be used to treat both estrogen receptor-positive and estrogen receptor-negative HER2-low breast cancers.
Trastuzumab deruxtecan increases survival better than standard chemotherapy in people who have HER2-low metastatic breast cancers that have progressed on different chemotherapy [42].
| For a summary of research studies on trastuzumab deruxtecan and metastatic breast cancer treatment, visit the Breast Cancer Research Studies section. |
Learn more about treatment for metastatic breast cancer.
Learn about emerging areas in treatment for metastatic breast cancer.
How is trastuzumab deruxtecan given?
Trastuzumab deruxtecan is given through an IV into a vein.
Side effects of trastuzumab deruxtecan
Before you begin treatment with trastuzumab deruxtecan, talk with your health care provider about possible side effects and how to manage them.
|
Side Effects |
Trastuzumab deruxtecan |
Possible side effects include low white blood cell counts, anemia (low red blood cell counts), nausea, vomiting, fatigue, hair loss, constipation and diarrhea. Trastuzumab deruxtecan can cause lung problems that can lead to breathing difficulty and death. You will be checked throughout your treatment for signs and symptoms of new or worsening breathing problems. Tell your health care provider right away if you have shortness of breath, cough or other breathing problems while taking this drug. Because trastuzumab deruxtecan contains trastuzumab, it can also cause serious heart problems. Discuss this risk with your health care provider before starting treatment. Your heart will be checked before and during treatment to help make sure there are no problems. |
|
Adapted from select sources [4,39]. |
|
Tyrosine-kinase inhibitors and metastatic breast cancer treatment
Tyrosine-kinase inhibitors are drugs that target tyrosine-kinase enzymes. These enzymes are important for cell functions. Tyrosine-kinase inhibitors can block tyrosine-kinase enzymes at many points along the cancer growth pathway.
The tyrosine-kinase inhibitors FDA-approved for metastatic breast cancer treatment are:
- Tucatinib (Tukysa)
- Neratinib (Nerlynx)
- Lapatinib (Tykerb)
A tyrosine-kinase inhibitor in combination with trastuzumab (Herceptin) and chemotherapy can be used to treat HER2-positive metastatic breast cancer. This combination may give women with HER2-positive metastatic breast cancer more time before the cancer worsens compared to treatment with trastuzumab and chemotherapy alone [43-48].
Adding the tyrosine-kinase inhibitor tucatinib to treatment with trastuzumab and chemotherapy may also increase overall survival in women with HER2-positive metastatic breast cancer who were treated with trastuzumab in the past, including those with spread of cancer to the brain [48-50].
| For a summary of research studies on the use of tucatinib in treating metastatic breast cancer, visit the Breast Cancer Research Studies section. |
| For a summary of research studies on the use of lapatinib in treating metastatic breast cancer, visit the Breast Cancer Research Studies section. |
Learn more about treatment for metastatic breast cancer.
Learn about emerging areas in treatment for metastatic breast cancer.
Learn about neratinib and treatment of early breast cancer.
Tucatinib, neratinib and lapatinib and brain metastases
Many drug therapies cannot pass through the blood to the brain (called the blood-brain barrier). So, they can’t treat breast cancer that has spread to the brain.
However, the tyrosine-kinase inhibitors tucatinib, neratinib and lapatinib can pass through the blood-brain barrier. So, they may be used to treat some metastatic breast cancers that have spread to the brain.
Adding tucatinib, neratinib or lapatinib to treatment may give women who have HER2-positive metastatic cancer with brain metastases more time before the cancer worsens [44-54]. Each drug may be given alone or in combination with chemotherapy and/or other HER2-targeted therapy.
How are tyrosine kinase inhibitors given?
The tyrosine kinase inhibitors tucatinib, neratinib and lapatinib are pills.
Side effects of tyrosine kinase inhibitors
Before you begin taking a tyrosine kinase inhibitor, talk with your health care provider about possible side effects and how to manage them.
Tyrosine-Kinase Inhibitors |
Side Effects |
Tucatinib, neratinib or lapatinib |
The most common side effect is diarrhea. Your health care provider will recommend medications to help prevent and control the diarrhea. Other possible side effects include nausea, vomiting, fatigue, abdominal pain and rash. In rare cases, each of these drugs has been linked to liver problems. Your liver function will be checked throughout your treatment to help make sure there are no problems. |
Adapted from select sources [43-45,48,51,55-56]. | |
Ashley Fernandez, living with metastatic breast cancer
“What keeps me going is my new normal. My life with cancer is completely different, I know I have it and I live with it every single day but it doesn’t take over every single day.”
Treatment guidelines for metastatic breast cancer
Although the exact treatment for metastatic breast cancer varies from person to person, guidelines help make sure high-quality care is given. These guidelines are based on the latest research and agreement among experts.
The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) are respected organizations that regularly review and update their guidelines.
In addition, the National Cancer Institute (NCI) has treatment overviews.
Talk with your health care team about which treatment guidelines they follow.
Clinical trials
Clinical trials offer the chance to try new treatments and possibly benefit from them.
Many clinical trials are available. Some are available as the first treatment for metastatic breast cancer. Others are for treatments later in the disease course. Consider joining a clinical trial when you’re newly diagnosed, when your oncologist is considering changing treatments or when there are limited treatment options.
Susan G. Komen® Patient Care Center |
If you or a loved one needs information or resources about clinical trials, the Patient Care Center can help. Contact the Komen Breast Care Helpline at 1-877-465-6636 or email clinicaltrialinfo@komen.org. Se habla español. |
Metastatic Trial Search |
The Metastatic Trial Search is a web-based clinical trial matching tool that can help you find clinical trials that fit your needs. You can also register to receive Trial Alerts. |
Learn more about clinical trials for people with metastatic breast cancer.
Financial assistance
Costs related to metastatic breast cancer care can quickly become a financial burden. Dealing with finances and insurance can be overwhelming. Cancer or its treatments may also keep you or your partner from working as much as you used to, which can affect your income.
Many cancer centers have financial counselors who can discuss insurance and cost coverage with you.
Learn about insurance plans and prescription drug assistance programs.
Learn about other financial assistance programs.
Komen Financial Assistance Program |
Susan G. Komen® created the Komen Financial Assistance Program to help those struggling with the costs of breast cancer treatment by providing financial assistance to eligible individuals. To learn more about this program and other helpful resources, call the Komen Breast Care Helpline at 1-877 GO KOMEN (1-877-465-6636) or email helpline@komen.org. Se habla español. |
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Susan G. Komen®‘s position on fairness in oral cancer drug coverage |
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Insurance coverage of oral cancer drugs Cancer medications given through an IV into a vein or by an injection (under the skin or into a muscle) are usually covered under a health insurance plan’s medical benefit. However, cancer medications that are pills (oral cancer drugs) are usually covered under a health insurance plan’s prescription drug benefit. As a result, people often find themselves facing high out-of-pocket costs when filling prescriptions for oral cancer drugs. Sometimes these costs can be thousands of dollars a month. The impact of high cost-sharing High prescription drug costs and the resulting out-of-pocket burden on patients are a barrier to care. They can prevent people from getting the medications prescribed by their health care providers. No one should be forced to get less appropriate treatment because an insurer gives more coverage for IV and injectable drugs than for pills. Efforts to increase fairness in drug coverage Komen supports state and federal efforts to require insurers to provide the same or better coverage for oral cancer drugs as they do for IV and injectable cancer drugs. This would help make sure patients have access to affordable, appropriate treatment. Become a Komen Advocacy Insider Sign up to be a Komen Advocacy Insider and get informed when action is needed on drug coverage issues at the state or national level. |
SUSAN G. KOMEN® METASTATIC BREAST CANCER SUPPORT RESOURCES |
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Updated 03/25/24
