Trastuzumab represents a significant advancement in the treatment of certain cancers, particularly those linked to a specific protein. This medication is a type of targeted therapy, designed to precisely attack cancer cells while minimizing harm to healthy ones. As a monoclonal antibody, it functions by mimicking the body’s natural immune system proteins, offering a more focused approach to fighting cancer compared to traditional methods.
Understanding Trastuzumab
Trastuzumab is a humanized monoclonal antibody that specifically targets the Human Epidermal growth factor Receptor 2 (HER2) protein. This protein, found on the surface of both healthy cells and some cancer cells, plays a role in cell growth and division. In certain cancers, there is an excessive amount of HER2 protein, known as overexpression or gene amplification, which can lead to uncontrolled cell proliferation and tumor growth.
Trastuzumab works by binding to the extracellular domain of the HER2 receptor on cancer cells. This binding inhibits the HER2 receptor’s ability to form active pairs, a process known as dimerization, which is necessary for activating growth signals within the cell. By blocking these signaling pathways, trastuzumab helps to slow down or stop the growth of HER2-positive cancer cells.
Beyond directly inhibiting HER2 signaling, trastuzumab also has other anti-tumor effects. It can mark the cancer cell for destruction by the body’s immune system, a process called antibody-dependent cellular cytotoxicity (ADCC). This means the drug helps the immune system recognize and attack the cancerous cells. Additionally, it may prevent the shedding of the HER2 extracellular domain, which has been linked to poorer outcomes in some cancers.
Cancers Treated
Trastuzumab is approved for the treatment of specific types of cancer that show overexpression of the HER2 protein. Its primary application is in HER2-positive breast cancer, encompassing both early-stage disease and metastatic forms that have spread to other parts of the body. In early breast cancer, it can be used before or after surgery, often in combination with chemotherapy.
The medication is also approved for treating HER2-positive metastatic gastric (stomach) cancer or gastroesophageal junction adenocarcinoma, which is cancer located where the esophagus meets the stomach. For these gastric cancers, trastuzumab is typically used in combination with chemotherapy for patients who have not received prior treatment for their metastatic disease. HER2 overexpression is found in a notable percentage of gastric cancers, similar to breast cancer, making trastuzumab a viable treatment option for these patients.
What to Expect During Treatment
Trastuzumab is typically administered as an intravenous (IV) infusion, meaning it is delivered directly into a vein. The infusions usually take place in an infusion center or a hospital setting. The initial dose, sometimes called a loading dose, may be given over a longer period, such as 90 minutes, with subsequent doses potentially administered over 30 to 90 minutes.
The frequency of treatment can vary, but it is commonly given weekly or every three weeks, depending on the specific treatment plan and cancer type. The total duration of trastuzumab therapy can range from several months to a year, or even longer in some metastatic settings, as determined by the healthcare team. Patients are closely monitored during and after infusions for any immediate reactions.
Patients may experience various side effects during trastuzumab treatment. Common reactions, particularly with the first infusion, can include fever, chills, nausea, headache, and rash. These infusion-related symptoms are usually mild to moderate and tend to become less frequent with subsequent doses. Other common side effects reported are fatigue, diarrhea, muscle and joint pain, and cough.
A more serious, though less common, potential side effect is cardiac dysfunction, which can manifest as a decrease in the heart’s pumping ability or, in rare cases, congestive heart failure. Patients are routinely monitored for heart function through tests like echocardiograms or MUGA scans before and during treatment. Lung issues, such as interstitial pneumonitis, are also rare but serious adverse effects that require immediate medical attention.
Who Benefits from Trastuzumab
The benefit from trastuzumab is directly linked to the presence of HER2 protein overexpression or gene amplification in cancer cells. Therefore, before a patient can receive trastuzumab, their tumor tissue must undergo specific laboratory testing to determine its HER2 status.
The two main methods for this are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
IHC testing assesses the amount of HER2 protein on the cell surface, with results typically graded from 0 to 3+. A score of 3+ generally indicates HER2 overexpression, making the patient a candidate for trastuzumab. If the IHC result is equivocal, often a 2+, or if there are other clinical considerations, FISH testing is performed. FISH directly looks for amplification of the HER2 gene within the cancer cells.
Only patients whose cancers are confirmed as HER2-positive through these tests are considered candidates for trastuzumab. Treatment decisions are always made by a multidisciplinary healthcare team.