HER2-neu Positive Breast Cancer Available Therapies
HER2-neu positive breast cancer used to be very aggressive and deadly prior to HER2-neu targeted therapy development.
Herceptin was the first monoclonal antibody targeting HER2-neu receptor improving by 38% patient survival in the adjuvant setting. The drug was tested and approved for the metastatic setting in the late 1990s. Herceptin binds to the extracellular portion of the HER2-neu receptor. Herceptin combined with adriamycin can cause 25% cardiotoxicity (weakening of the heart), but if combined with taxotere and carboplatin the cardiotoxicity is less than 3%. Herceptin is intravenous.
The second generation HER2-neu inhibitor developed was tykerb, a tyrosine-kinase inhibitor, which binds to the intracellular portion of the HER2-neu receptor. Tykerb blocks cell growth; it is in a pill form therefore very convenient. Major side effects are hand foot syndrome and diarrhea, which is manageable.
Following tykerb, T-DM1 was developed, which is an antibody drug conjugate. The way the drug works is that herceptin binds the HER2-neu receptor and the emtansine chemotherapy is then introduced into the cancer cell causing cell deaths. The toxicity of this drug is very limited with decrease of the platelets but no nausea, vomiting or hair loss occurred.
The latest drug approved for HER2 positive metastatic breast cancer is pertuzmab, also a monoclonal antibody targeting HER2-neu but in a different way compared to herceptin. Ongoing trials using the combination of herceptin and pertuzmab seem to show better results compared to single agents. Major side effects are rash, diarrhea and mouth sores. Currently, vaccines targeting HER2-neu proto-oncogene are being tested with promising responses. Dendritic cell specific antibodies fused with the HER2-neu protein are soon to be tested in the clinical setting. Drug development continues to improve survival for HER2-neu positive breast cancer patients in the adjuvant and metastatic setting.