Risks Linked With Specific Treatments

This section covers the different types of HER2-targeted therapies and concerns associated with them.

Trastuzumab (Herceptin®): The oldest and most widely studied HER2-targeted therapy is trastuzumab. Trastuzumab was first approved for use in patients with metastatic HER2-positive breast cancer in 1998 and is used to treat various stages of HER2-positive breast cancer. Trastuzumab may reduce the risk of death or slow the progress of breast cancer by up to 50%. Cardiotoxicity from trastuzumab is uncommon when it is used in young and healthy patients, without other heart risk factors (for example, high blood pressure, high cholesterol or diabetes), and who are not receiving other cardiotoxic drugs. However, cardiotoxicity from trastuzumab may occur at much higher rates (20% to 40% of patients) when used in combination with cardiotoxic chemotherapy (especially those containing agents called anthracyclines), in patients who are older, have several heart risk factors or already have heart disease.

Pertuzumab (Perjeta®): The combination of pertuzumab and trastuzumab with chemotherapy is most often used in patients with metastatic HER2-positive disease, or before surgery for patients with earlier stages of HER2-positive breast cancer. The addition of pertuzumab to trastuzumab does not appear to increase the risk of cardiotoxicity beyond that linked with trastuzumab alone.

Lapatinib (Tykerb®): Lapatinib is an oral HER2-targeted therapy sometimes used in patients with metastatic HER2-positive breast cancer that continues to grow and spread despite treatment with therapies including trastuzumab. In this setting, adding lapatinib may prevent the cancer from spreading. The impact of lapatinib on the heart has been studied less than trastuzumab; however, the available data suggest lapatinib has a low risk of cardiotoxicity.

Ado-trastuzumab emtansine (Kadcyla®): Ado-trastuzumab emtansine is a combination of trastuzumab and a chemotherapy called emtansine. It is approved for use in patients with metastatic breast cancer who have had tumor growth despite treatment with therapies including trastuzumab. As is the case for lapatinib, ado-trastuzumab emtansine appears to cause less cardiotoxicity than trastuzumab. However, its effects on the heart have been less studied than trastuzumab.

Neratinib (Nerlynx®): Neratinib is a recently approved oral HER2-targeted treatment that can be used in patients with early breast cancer who have completed one year of trastuzumab. It helps lower the chance the cancer will return. Neratinib does not appear to be cardiotoxic.

Other Cardiotoxic Medications

The risk of cardiotoxicity from HER2-targeted therapies is greatest when it is used with anthracyclines. Two major drugs are in this class: doxorubicin and epirubicin. Anthracyclines are effective in treating breast cancer. Unfortunately, they also can cause cardiotoxicity. The risk is greater when high doses are given (>250 mg/m2 of doxorubicin or >600 mg/m2 of epirubicin). The use of trastuzumab at the same time or after anthracyclines increases the risk of poor heart function or development of heart failure.

Today, anthracyclines usually are given in low doses or aren't given at the same time as HER2-targeted therapy to reduce the risk of heart damage. Radiotherapy may also be linked with heart damage, although more research is needed to find out how much risk is added when used with HER2-targeted therapy.