HER2 Positive Metastatic Breast Cancer

By Isabella Martire, MD, Board Certified In Oncology

Isabella C. Martire, MD, AC

. https://www.isabellamartire-md.com/

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HER2 Positive Metastatic Breast Cancer

Anti-HER2 therapies have greatly improved survival rates in HER2 positive breast cancer. First line therapy for advanced HER2 positive breast cancer is the combination of the monoclonal antibodies trastuzmab, pertuzmab and a taxane.

Herceptin (trastuzmab) is a humanized IgG1 monoclonal antibody that binds to the extracellular domain of the HER2 receptor it is given intravenously. Herceptin is generally well tolerated. Cardiomyoapathy, infusion reaction and pulmonary toxicity can occur requiring discontinuation of the drug.

Pertuzmab (Perjeta) is also a monoclonal antibody that targets the HER2 receptor on the surface of the cancer cells. Pertuzmab and trastuzmab bind to different areas of the HER2 receptor resulting in a complete blockage of the HER2 signaling with improved efficacy. The most common side effects are diarrhea, fatigue, nausea, rash, numbness of hands and feet, and less often, allergic reactions.

Pertuzmab and trastuzmab are given in combination with taxotere (docetaxel).

Taxotere is a chemotherapy that was approved for breast cancer many years ago and was given in combination with pertuzmab and trastuzmab in the Cleopatra trial which revealed a 56.5 months median survival in the group receiving pertuzmab compared to 40 months in the group without pertuzmab.

T-DMI or trastuzmab emtansine is the standard second line therapy based on the Emilia trial. T-DMI is the antibody trastuzmab linked to the cytotoxic agent emtansine. This agent revealed prolonged overall survival and disease free survival in metastatic breast cancer. Trastuzmab binds to HER2 receptor facilitating the entry of the cytotoxic agent emtansine into the cells binding to tubulin, which results in the distribution of the cells. The most common side effects of T-DMI are fatigue, thrombocytopenia, H/A, nausea, joint muscle pain. The liver enzyme needs to be monitored for possible toxicity.

The next class of drugs being tested are the tyrosine kinase inhibitors targeting HER1, HER2 and HER4. Neratinib is currently in phase three trials, and tucatinib is in phase 2 trials. New antibody/drug conjugates are being tested as well.