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About 1 of every 5 breast cancers contain cells with extra copies of the gene that makes the human epidermal growth factor receptor 2 (HER2) protein. These HER2-positive breast cancers tend to be more aggressive than other types of breast cancer.
However, over the past two decades, new medicines have transformed the treatment of this form of breast cancer. The first HER2-targeted therapy, trastuzumab (Herceptin) combined with chemotherapy, improved overall survival outcomes of these cancers by 30% and reduced the risk of recurrence by 50%, says Mayo Clinic oncologist Ciara O’Sullivan, M.B., B.Ch.
What are HER2-targeted therapies?
Traditional chemotherapy, radiation and surgery still play an important role in the treatment of HER2-positive cancers. These treatments often are used along with newer treatments that target HER2-positive cancer in slightly different ways. There are three main types of HER2-targeted therapies.
Monoclonal antibodies
Monoclonal antibodies are the most common HER2-targeted therapies. These mimic the antibodies made by the immune system. When given as an infusion, these antibodies attach to the HER2 receptors on cancer cells, stopping them from receiving signals. They also engage the body’s immune system to destroy cancer cells. These actions help prevent the cancer cells from multiplying and promote cancer cell death.
Monoclonal antibody HER2-targeted medicines include:
- Trastuzumab (Herceptin), available as an infusion or injection and used to treat early-stage and advanced breast cancer.
- Pertuzumab (Perjeta), an infusion that is often combined with trastuzumab and chemotherapy to treat early-stage or advanced breast cancer.
- Margetuximab (Margenza), an infusion that is usually combined with chemotherapy to treat advanced breast cancer.
Tyrosine kinase inhibitors
Kinase is a protein that tells cells to grow. Tyrosine kinase inhibitors block this protein, interrupting the signal and helping to stop cancer growth. This class of HER2-targeted medicines includes the following:
- Lapatinib (Tykerb), a pill taken daily for people with advanced breast cancer.
- Neratinib (Nerlynx), a pill taken daily for people with early-stage breast cancer and metastatic breast cancer that has not responded to other HER2-targeted medicines.
- Tucatinib (Tukysa), a pill taken twice a day for advanced breast cancer after someone has tried at least one other HER2-targeted medicine.
Antibody-drug conjugates (ADCs)
These medicines combine monoclonal antibodies with chemotherapy agents. The antibodies attach to the HER2 protein and help the chemotherapy agent get inside the cancer cell and kill it. They include the following:
- Ado-trastuzumab emtansine (Kadcyla), an infusion used to treat some early-stage breast cancers and some advanced breast cancers.
- Trastuzumab deruxtecan (Enhertu) — often abbreviated to T-DXd — is an infusion used to treat advanced breast cancers. Healthcare professionals also use this medicine to treat some HER2-low breast cancers. These cancers express a lower level of the HER2-protein compared with HER2-positive cancers.
What are the side effects of HER2-targeted therapies?
For optimal effectiveness, most HER2-targeted therapies are paired with chemotherapy, especially during treatment of early-stage breast cancer. That means you can expect the typical side effects of chemotherapy along with the potential side effects of HER2-targeted therapy. These include the following:
- An increased risk of cardiac toxicity in people taking monoclonal antibodies. Though serious, this side effect is rare and often reversible. Your medical team may monitor your heart regularly on treatment with a test called an echocardiogram.
- Diarrhea and rashes in people taking tyrosine kinase inhibitors.
- An increased risk of lung disease in people taking antibody-drug conjugates. As a result, your healthcare professional may monitor you for cough, shortness of breath, fever and other respiratory symptoms during your treatment.
Keep in mind that some people notice minimal or mild side effects on therapy, says Dr. O’Sullivan. In addition, healthcare professionals can help manage treatment-related symptoms by reducing the dose of a medication, shortening the duration or switching to an alternative.
Which targeted therapy is suitable for me?
Healthcare professionals may recommend a targeted therapy based on what breast cancer treatments you’ve already tried, the stage of your disease, your overall health, and many other factors, says Dr. O’Sullivan. For example:
- A small tumor that hasn’t spread outside the breast. Surgery may be recommended, followed by chemotherapy, and one or more monoclonal antibody medicines. After chemotherapy is finished, a maintenance dose of the HER2-targeted therapy is used for about a year in total.
- A larger tumor that has spread to the armpit. The first recommendation may be to try chemotherapy and one or more monoclonal antibody medicines to shrink the tumor and see how it responds. This may be followed by surgery and a maintenance dose of the HER2-targeted therapy for about a year in total. Other treatments after surgery such as radiation therapy or hormone-blocking therapies or both may be used.
- Advanced cancer that has spread to other parts of the body. HER2-targeted therapies are likely to be recommended, either alone or combined with chemotherapy or hormone-blocking therapies, switching among them based on how the cancer responds on follow-up scans. Surgery and radiation therapy may not be recommended if the tumor has spread outside the breast and armpit to other parts of the body. Chemotherapy coupled with two monoclonal antibodies may be used initially and then switched to a kinase inhibitor, chemotherapy and a monoclonal antibody, for example.
Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission.
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