Targeted therapies 

Activity of the human epidermal growth factor receptor 2 (HER2) protein mediates the growth of cells. In HER2 positive cancer cells, HER2 is produced in high amounts leading to accelerated growth, survival, and metastasis.  

Anti-HER2 targeted therapies

Anti-HER2 antibodies 

Trastuzumab works by binding to HER2 at the cancer cell surface and thereby slows the growth of HER2 positive breast cancers. 

Pertuzumab acts similar to trastuzumab but binds to a different part of the HER2 protein slowing the growth of HER2 positive breast cancers. Pertuzumab and trastuzumab can be used in combination, which is called a dual HER2 blockade, and its effect is significant in treating metastatic breast cancer. when used in the first cancer treatment the patient receives (first-line therapy).  

Known side effects for anti-HER2 therapeutics are cardiomyopathy, infusion reactions, pulmonary toxicity and decreased amniotic fluid for gestational age. The risk for cardiac dysfunction depends on the chemotherapeutic regime. In addition, diarrhea is frequently reported.  

Margetuximab is related to trastuzumab and binds in addition to the HER2 protein of the cancer cell, to a protein located at the immune cell surface. This leads to an attack from the immune cell on the tumour cell.  

Side effects of Margetuximab treatment include fatigue, nausea, diarrhea, and low number of immune cells.  

HER2 antibody-drug conjugates 

Trastuzumab emtansine is an antibody-drug conjugate between trastuzumab and the anticancer agent , DM1. The antibody-receptor complex is taken up by the tumour cell and an active DM1 metabolite is released leading to cancer cell death.  

Trastuzumab deruxtecan is an antibody-drug conjugate comprised of trastuzumab and the anticancer agent, deruxtecan.  

Side effects of HER2 antibody-drug conjugates are thrombocytopenia meaning low platelets, which can result in bleeding issues and impairment of liver function (hepatotoxicity) and hematologic toxicities. Hematologic toxicities decrease production of red blood cells (causing anemia) and white blood cells (neutropenia/leukopenia). Furthermore, gastrointestinal side effects are possible (more common with trastuzumab deruxtecan), nausea, hair loss and inflammation in your lung tissues without an infection (pneumonitis).