Trastuzumab, also known as Herceptin, is a monoclonal antibody used to treat HER2-positive breast cancer and certain types of stomach cancer (National Cancer Institute, n.d.). HER2-positive breast cancer occurs when cells produce too much human epidermal growth factor receptor 2 (HER2), a protein that promotes cancer cell growth. Approximately 25-30% of breast cancer cases are HER2-positive, making this an important target for treatment (Slamon et al., 2001). Trastuzumab attaches to HER2 receptors on cancer cells, blocking their growth signals and helping the immune system recognize and destroy these cells. It is often used in combination with chemotherapy to increase effectiveness, particularly in early-stage and metastatic breast cancer (Piccart-Gebhart et al., 2005). Studies show that patients receiving Trastuzumab alongside chemotherapy have higher survival rates and a lower risk of cancer recurrence compared to those receiving chemotherapy alone (Hudis, 2007). However, the drug is not without risks, as some patients experience side effects such as heart problems, fever, nausea, and fatigue (National Cancer Institute, n.d.). The potential for heart damage is a significant concern, so doctors regularly monitor heart function during treatment (Seidman et al., 2002). Despite these risks, Trastuzumab has revolutionized the treatment of HER2-positive breast cancer, improving outcomes for thousands of patients worldwide and providing hope as researchers look for a cure for cancer. As research continues, newer versions of HER2-targeted therapies are being developed to make treatment even more effective with fewer side effects (Swain et al., 2013).

Trastuzumab belongs to the IgG class of antibodies, which is the most common type found in human blood and extracellular fluid (Vidarsson et al., 2014).

Trastuzumab works by targeting the HER2 protein found on cancer cells. In normal cells, HER2 plays a role in cell growth and repair, but when too much HER2 is present, it causes cells to divide uncontrollably, leading to aggressive tumor growth (Hudis, 2007). Trastuzumab binds directly to HER2, blocking the signals that tell the cancer cells to grow. This prevents further tumor growth and, in some cases, leads to tumor shrinkage (National Cancer Institute, n.d.). Additionally, Trastuzumab activates the body’s immune system, marking the HER2-positive cancer cells for destruction by immune cells. This process, called antibody-dependent cellular cytotoxicity (ADCC), enhances the body’s ability to fight cancer (Seidman et al., 2002).

In addition to blocking HER2 signaling, Trastuzumab prevents HER2 from pairing with other growth-promoting proteins on the cell surface, further reducing cancer cell survival (Swain et al., 2013). Studies have shown that patients treated with Trastuzumab have significantly improved survival rates, with a 50% reduction in cancer recurrence risk in early-stage cases (Piccart-Gebhart et al., 2005). However, some patients develop resistance to Trastuzumab over time, leading researchers to explore combination therapies with other HER2-targeted drugs, such as Pertuzumab and T-DM1 (Swain et al., 2013). Another major concern is cardiotoxicity, as Trastuzumab can weaken the heart muscle, particularly in patients who already have heart disease or receive anthracycline-based chemotherapy (Seidman et al., 2002). Despite these risks, Trastuzumab remains a gold-standard treatment for HER2-positive cancer, dramatically improving patient outcomes and survival rates.

References

Hudis, C. A. (2007). Trastuzumab—Mechanism of action and use in clinical practice. New England Journal of Medicine, 357(1), 39-51. https://doi.org/10.1056/NEJMra043186 

National Cancer Institute. (n.d.). Trastuzumab (Herceptin). Retrieved from https://www.cancer.gov/about-cancer/treatment/drugs/trastuzumab 

Piccart-Gebhart, M. J., Procter, M., Leyland-Jones, B., Goldhirsch, A., Untch, M., Smith, I., Gianni, L., Baselga, J., Bell, R., Jackisch, C., Cameron, D., Dowsett, M., Barrios, C., & Slamon, D. J. (2005). Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. New England Journal of Medicine, 353(16), 1659-1672. https://doi.org/10.1056/NEJMoa052306 

Seidman, A., Hudis, C., Pierri, M. K., Shak, S., Paton, V., Ashby, M., Murphy, M., Stewart, S. J., & Keefe, D. (2002). Cardiac dysfunction in the trastuzumab clinical trials experience. Journal of Clinical Oncology, 20(5), 1215-1221. https://doi.org/10.1200/JCO.2002.20.5.1215 

Slamon, D. J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Eiermann, W., Wolter, J., Pegram, M., Baselga, J., & Norton, L. (2001). Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. New England Journal of Medicine, 344(11), 783-792. https://doi.org/10.1056/NEJM200103153441101 

Swain, S. M., Baselga, J., Kim, S. B., Ro, J., Semiglazov, V., Campone, M., Ciruelos, E., Ferrero, J. M., Schneeweiss, A., Heeson, S., Clark, E., Ross, G., Benyunes, M. C., Cortés, J., & CLEOPATRA Study Group (2015). Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. The New England journal of medicine, 372(8), 724–734. https://doi.org/10.1056/NEJMoa1413513 Vidarsson, G., Dekkers, G., & Rispens, T. (2014). IgG subclasses and allotypes: From structure to effector functions. Frontiers in Immunology, 5, 520. https://doi.org/10.3389/fimmu.2014.00520