Tumours with HER2 amplification or overexpression are highly likely to be sensitive to HER2 targeted agents. In current clinical practice, HER2 amplification or overexpression is performed in breast, gastric, and gastro-oesophageal cancers. Recent studies have suggested that mutations can also activate the HER2 gene, and these activating mutations might be similarly sensitive to HER2 inhibitors. Furthermore, these studies have identified activating mutations of HER2 across different tumour types and suggested they might be implicated in tumourigenesis.
Targeted HER2 agents are approved by medical regulatory bodies and recommended in the clinical practice guidelines for the treatment of breast, gastric, and gastro-oesophageal cancers that overexpress or amplify HER2, as measured by immunohistochemistry and in situ hybridization (ISH), respectively. Testing for HER2 mutations is not performed routinely, especially not outside the currently approved indications for HER2 targeted agents.
Recent studies suggest that a more comprehensive molecular profiling of multiple tumour types has the potential to identify additional patients who may derive clinical benefit from already existing or HER2 targeted agents in development. This V-learning module has been initiated to draw attention to such possibility and summarize the current evidence, as cancer treatment is moving towards personalised therapies. Critical to this effort is the reliable identification of driver alterations and therapeutics that can effectively inhibit their activity.
In this V-Learning module, the author introduces the magnitude of HER2 mutations, as well as the results from recent and ongoing studies in breast, lung, colorectal and other cancer types. Routine slide based tests assess only the HER2 gene amplification or protein overexpression and would fail to detect the majority of activating mutations. The author provides current evidence on 2 critical questions, which are currently under investigation: 1) Whether HER2 mutations can be used to select patients for anti-HER2 treatment alone or in combination, and 2) what is the predictive value of different HER2 mutations in different cancer types. Furthermore, he presents challenges for moving the next generation sequencing data to the clinic.
