According to Genentech’s website, Herceptin (Trastuzumab) is a monoclonal antibody drug approved for the treatment of “early-stage breast cancer that is Human Epidermal growth factor Receptor-positive (HER2+),” “HER2+ metastatic breast cancer,” and “HER2+ metastatic cancer of the stomach or gastroesophageal junction” (in certain cases). Monoclonal antibodies are “laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance or mimic the immune system’s attack on cancer cells.” These man-made antibodies are designed to target antigens that only exist on, or are more numerous on, cancer cells relative to healthy cells. This allows the treatment to be more targeted against cancer cells, unlike many chemotherapy and radiation treatments that indiscriminately affect cancer and healthy cells. Antibodies are a natural part of the immune system, and when they attach to cancer cells, they can serve as flags to attract cells of the immune system or trigger cell destruction. However, cancer can spread too quickly or be otherwise resistant to our own natural immune systems. This is when we need treatments like monoclonal antibodies to help make up the difference.
Herceptin is a treatment option for those who have over-expression of Human Epidermal growth factor Receptor (HER2+). HER2 receptors are found on normal cells, and play a role in cell growth. Over-expression of HER2 receptors is found in about 20-30% of all breast cancers, and they are partially responsible for the increased growth and development of cancer cells. If HER2 is over-expressed (present in large amounts), the cancer cells may grow and spread faster. Under normal circumstances, the immune system would detect and attack cells with HER2 receptors, but if there are too many the immune system may not keep up. Herceptin is a man-made antibody that targets HER2 receptors and blocks them, stunting cancer growth and drawing the attention of white blood cells to induce cell death.
The website for Herceptin provides a laundry list of potential side effects, including:
- Heart problems, including congestive heart failure and reduced heart function
- Fever and chills
- Feeling sick (nausea)
- Throwing up (vomiting)
- Pain (sometimes at tumor sites)
- Headache
- Dizziness
- Shortness of breath
- Death of an unborn baby
- Birth defects
- Severe shortness of breath
- Fluid in or around the lungs
- Weakening of the valve between the heart and the lungs
- Not enough oxygen in the body
- Swelling of the lungs
- Scarring of the lungs
- Low white and red blood cell counts
- Diarrhea
- Infections
- Increased cough
- Feeling tired
- Rash
- Muscle pain
- Swelling of the mouth lining/mucous membranes/nose and throat
- Weight loss
- Low platelet counts
- Change in taste
Most of these side effects are manageable, and the most serious side effects are seen in a lower percentage of women treated with Herceptin. Years ago, my grandmother was diagnosed with stage 2 breast cancer, and after her surgery to remove the tumors, she took Herceptin for a year through weekly IV infusions. She qualified because she had HER2 over-expression, and the drug worked very well for her. She remembers that at the time, it was still a “new” drug, but it was an appealing option because it was a pioneer drug for targeted treatment. This usually means that there are less side effects than for more traditional cancer treatments. For the most part, her only side effects were flu-like symptoms. People who are high risk for more serious side effects such as heart problems (already have underlying heart conditions) are monitored carefully and checked regularly.
Herceptin can make the patient more susceptible to infection because it can lower their white blood cell count, and your white blood cells are a very important part of your immune system. Specifically, this review and meta-analysis found that patients treated with Trastuzumab were higher risk for infection and febrile neutropenia. Febrile neutropenia is the occurrence of fever during a period of lowered neutrophil count in the blood. Neutrophils are the most abundant type of white blood cell, and are a vital part of the innate immune system. This issue can be amplified when Herceptin is combined with another traditional chemotherapy, which more broadly affects cancerous and healthy cells.
In addition to slowing cancer growth by blocking HER2 receptors, anti-HER2 monoclonal antibodies also activate both the innate and acquired immune system. They induce granzyme release by Natural Killer (NK) cells, which increases induced cell death in the cancer cells. The Trastuzumab-HER2 complexes that are made are internalized by the cancer cells, which allows for degradation and presentation of HER2 fragments in MHC class I molecules. This signals to cytotoxic T cells that the cell needs to be killed, so the T cells induce apoptosis in these cells.
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