HER2-Targeted Therapies for Metastatic Breast Cancer

HER2-positive breast cancer

HER2 is a protein that’s important for cancer cell growth. HER2-positive breast cancers have high amounts of HER2 on the surface of the cancer cells. You may also hear the term HER2 over-expression.

A pathologist determines HER2 status by testing tumor tissue removed during a biopsy.
About 10-20 percent of breast cancers are HER2-positive [22-23]. 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 by vein through an IV)?

Trastuzumab

Herceptin (IV drug) and Herceptin Hylecta (injection)

IV drug or injection

Pertuzumab

Perjeta (IV drug) and Phesgo (injection combined with trastuzumab)

IV drug or when combined with trastuzumab, injection

Margetuximab

Margenza

IV drug

Ado-trastuzumab emtansine (T-DM1)

Kadcyla

IV drug

Trastuzumab deruxtecan (fam-trastuzumab deruxtecan)

Enhertu

IV drug

Tucatinib

Tukysa

Pill

Neratinib

Nerlynx

Pill

Lapatinib

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 it’s no longer working, or if the side effects are not manageable, your health care provider will change your treatment.

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. When attached to the HER2 protein, trastuzumab can slow or stop the growth of these cells.

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 [24-26].

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For a summary of research studies on trastuzumab and treatment for 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 by vein (through an IV) or by injection under the skin.

Side effects of trastuzumab

Side Effects

Trastuzumab

Possible side effects include headache, fever and chills.

It does not cause hair loss, nausea or vomiting, and has no effect on bone marrow.

Trastuzumab can cause serious heart problems. Your heart will be checked before and during treatment to help ensure there are no problems.

Adapted from select sources [4,24].

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 some FDA-approved biosimilar forms of trastuzumab. These 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 [27-28].

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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. Pertuzumab can be given by vein (through an IV) or, when combined into one drug with trastuzumab (called Phesgo), it may be given by injection under the skin.

Side effects of pertuzumab

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 ensure there are no problems.

Adapted from select sources [27-28].

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 spreads compared to trastuzumab in combination with chemotherapy [29].

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 by vein (through an IV).

Side effects of margetuximab

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 ensure there are no problems.

Adapted from select sources [29-30].

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 [31].

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 by vein (through an IV).

Side effects of ado-trastuzumab emtansine

Side Effects

Ado-trastuzumab emtansine

Possible side effects include nausea, fatigue, muscle and joint pain, neuropathy, low platelet counts and headache.

It can also cause liver problems. Your liver will be checked before and during treatment to help ensure there are no problems.

It doesn’t usually cause hair loss.

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 ensure there are no problems.

Adapted from select sources [32].

Trastuzumab deruxtecan (Enhertu, fam-trastuzumab deruxtecan)

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 past HER2-targeted therapy for metastatic breast cancer.

Study findings show trastuzumab deruxtecan may help shrink tumors in some women with metastatic HER2-positive breast cancers [33].

Study findings also show that trastuzumab deruxtecan may increase overall survival in people with metastatic breast cancer better than ado-trastuzumab emtansine (Kadcyla, T-DM1) [76].

Further, some study findings show trastuzumab deruxtecan be effective in treating some metastatic breast cancers that have spread to the brain [76].

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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 by vein (through an IV).

Side effects of trastuzumab deruxtecan

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.

It 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 ensure there are no problems.

Adapted from select sources [33].

Tyrosine-kinase inhibitors and metastatic breast cancer treatment

Tyrosine-kinase inhibitors are drugs that target tyrosine-kinase enzymes, which are important for cell functions. These drugs 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 spreads compared to treatment with trastuzumab and chemotherapy alone [34-39].

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 [39].

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For a summary of research studies on the use of tucatinib in treating metastatic breast cancer, visit the Breast Cancer Research Studies section.

 52829-3.gif

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, tyrosine-kinase inhibitors tucatinib, neratinib and lapatinib can pass through the blood-brain barrier. 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 spreads [39-43]. 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

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 control the diarrhea.

Other possible side effects include nausea, vomiting and fatigue.

In rare cases, each of these drugs has been linked to liver problems. Your liver function will be checked throughout your treatment to help ensure there are no problems.

Adapted from select sources [34-35,39-40,44-45].

Clinical trials

Clinical trials offer the chance to try new treatments and possibly benefit from them.

Consider joining a clinical trial when your oncologist is considering changing treatments, before starting a new treatment or when there are limited treatment options.

Susan G. Komen® Breast Care Helpline

If you or a loved one needs information or resources about clinical trials, call the Komen Breast Care Helpline at 1-877 GO KOMEN (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.

Learn more about clinical trials for people with metastatic breast cancer.

Prescription drug assistance

The cost of drug therapies for metastatic breast cancer can quickly become a financial burden for you and your family.

Medicare and many insurance companies offer prescription drug plans. One may already be included in your policy, or you may be able to buy an extra plan for prescriptions.

Some drugs are off-patent and may have a generic form. Generic drugs cost less than the name brands but are just as effective.

You may also qualify for programs that help with drug costs or offer low-cost or free prescriptions.

Learn more about insurance plans and prescription drug assistance programs.

Learn more 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.

Funding is available for eligible individuals undergoing breast cancer treatment at any stage or living with metastatic breast cancer (stage IV).

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.

Susan G. Komen®‘s position on fairness in oral cancer drug coverage

Insurance coverage of oral cancer drugs

Cancer medications given by vein (through an IV) or 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 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® SUPPORT RESOURCES

  • If you or a loved one needs more information about breast health or breast cancer, contact the Komen Breast Care Helpline at 1-877 GO KOMEN (1-877-465-6636) or email helpline@komen.org. All calls are answered by a trained specialist or oncology social worker, Monday through Friday from 9:00 a.m. to 10:00 p.m. ET. Se habla español.
  • Komen Patient Navigators can help guide you through the health care system as you go through a breast cancer diagnosis. They can help to remove barriers to high-quality breast care. For example, they can help you with insurance, local resources, communication with health care providers and more. Call the Komen Breast Care Helpline at 1-877 GO KOMEN (1-877-465-6636) or email helpline@komen.org to learn more about our Patient Navigator program, including eligibility.
  • We offer an online support community through our closed Komen Metastatic Breast Cancer group. The Facebook group provides a place where those living with metastatic breast cancer, and those who love them, can find support, friendship and information. Visit Facebook, search for Komen Metastatic Breast Cancer (Stage IV) Group and request to join the closed group.
  • Our free MBC Impact Series provides people living with metastatic breast cancer and their loved ones a safe, collaborative space to gather information related to MBC and discover practical resources to help make decisions for improved physical and emotional health. To learn more and register visit www.komen.org/mbcseries.
  • Our podcast series Real Pink covers many relevant topics for people living with metastatic breast cancer and caregivers.
  • Our fact sheets, booklets and other education materials offer additional information.
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*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.

Updated 07/08/22

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