Trastuzumab — Targeted Therapy for HER2-Positive Cancers

Trastuzumab is a humanised recombinant IgG1 monoclonal antibody that selectively targets the extracellular domain of the HER2 transmembrane protein kinase receptor. In normal tissues, HER2 helps regulate cell growth, but its amplification or overexpression drives aggressive oncogenic proliferation. By binding specifically to domain IV of HER2, trastuzumab blocks ligand-independent downstream signalling via the MAPK and PI3K/Akt pathways, which leads to cell cycle arrest.

In addition to inhibiting intracellular signalling pathways, trastuzumab mediates antibody-dependent cellular cytotoxicity (ADCC). This process tags HER2-overexpressing tumour cells for targeted destruction by natural killer (NK) cells and other immune effectors. Trastuzumab also suppresses vascular endothelial growth factor (VEGF) production, thereby impeding tumour-associated neoangiogenesis.

Before trastuzumab became available, HER2-positive breast cancer carried a poorer prognosis with high recurrence rates. The introduction of trastuzumab fundamentally altered this landscape, turning an aggressive subtype into one of the most treatable forms of breast cancer. For patients with early-stage disease, trastuzumab substantially reduces the risk of relapse, whilst in advanced stages, it extends overall survival. Determining your tumour's HER2 status is therefore one of the most critical diagnostic steps after diagnosis.

Before prescribing trastuzumab, pathology laboratories must verify HER2 protein overexpression or gene amplification. Testing is performed on tumour tissue biopsies using immunohistochemistry (IHC) and in situ hybridisation (ISH or FISH). A result of IHC 3+ or ISH-positive confirms HER2 positivity, indicating the patient is eligible for trastuzumab therapy.

Trastuzumab is primarily indicated for HER2-positive invasive breast cancer in both early, curative-intent settings and metastatic scenarios. It is also licensed for the treatment of HER2-positive metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Clinical trials frequently investigate its utility in other HER2-altered solid malignancies, including selected cases of salivary gland, colorectal, and non-small cell lung carcinomas.

Trastuzumab is frequently paired with cytotoxic chemotherapies, such as taxanes, because their combined action produces synergistic anti-tumour responses. In early breast cancer, it is typically administered for one full year. It can also be combined with pertuzumab for dual-HER2 blockade, or linked directly to cytotoxic agents to form antibody-drug conjugates like trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd).