Targeted therapy for HER2-positive breast cancer

Targeted treatments for HER2-positive breast cancer work by targeting the HER2 proteins or markers on or within cancer cells that help the cells to grow. They attach to HER2 proteins either on the inside or on the outside of a cancer cell and block signals that tell the cells to multiply too quickly.

In many cases, targeted therapies are given in combination with specific chemotherapy medicines, although some can be given alone for certain types of breast cancer. If you need radiation therapy as part of your treatment plan, it’s possible to receive targeted therapies at the same time, or after you’ve finished radiation treatments. Talk to your doctor about your individual situation.

In this section, you’ll learn more about the different classes of HER2-targeting medicines and how they work to treat breast cancer.

Monoclonal antibodies

Monoclonal antibodies are large molecules made in a lab that attack a specific protein on the outside of a cell. To your body, these molecules look similar to antibodies it makes to fight germs and infection. But monoclonal antibodies are designed to attach to a specific receptor found or overexpressed on cancer cells, such as the HER2 receptor in HER2-positive breast cancer.

Medicines in this class are given by vein or subcutaneous (under the skin) injection. Monoclonal antibodies used in breast cancer are:

• Trastuzumab (Herceptin)
• Pertuzumab (Perjeta)
• Margetuximab (Margenza)

Biosimilars of trastuzumab—drugs that are highly similar to trastuzumab and have the same effectiveness—are also approved to treat HER2-positive breast cancer. These medicines can be less expensive than trastuzumab, and they include:

• Trastuzumab-anns (Kanjinti)
• Trastuzumab-dkst (Ogivri)
• Trastuzumab-dttb (Ontruzant)
• Trastuzumab-qyyp (Trazimera)
• Trastuzumab-pkrb (Herzuma)
• Trastuzumab-strf (Hercessi)

Tyrosine kinase inhibitors

Tyrosine kinase inhibitors, or TKIs, are small molecules made in a lab. TKIs look for proteins called tyrosine kinases inside cancer cells that signal the cancer cells to grow. TKIs can block the activity of these tyrosine kinases in HER2-positive breast cancer so the cancer cell cannot grow and divide.

TKIs are given as pills. The FDA-approved medicines in this class for HER2-positive breast cancer are:

• Lapatinib (Tykerb)
• Neratinib (Nerlynx)
• Tucatinib (Tukysa)

Antibody-drug conjugates

Antibody-drug conjugates, or ADCs, deliver a powerful chemotherapy in a targeted way. The antibody is targeted at a protein on the surface of cancer cells (such as HER2). This antibody delivers the chemotherapy directly to the inside of the cancer cells. This helps limit the side effects of the chemotherapy on healthy cells.

There are many ADCs under study for different types of breast cancer, and there are now ADCs available for both HER2-positive and HER2-negative breast cancer. The FDA has approved several antibody-drug conjugates for HER2-positive breast cancer:

• Ado-trastuzumab emtansine (Kadcyla)
• Trastuzumab deruxtecan (Enhertu)

Trastuzumab deruxtecan is also FDA approved to treat metastatic breast cancers that have lower HER2 levels: HER2-low and HER2-ultralow.

HER2-targeted therapies and heart health

Targeted therapies for HER2-positive breast cancer can cause heart health side effects. Let your doctor know if you have any other health conditions already, especially heart conditions. Your healthcare team should monitor your heart health throughout treatment because of the risk for heart side effects. Ask them for a heart health follow-up plan once treatment ends.