Fast Five Quiz: ERBB2 (HER2) Mutation in Non-Small Cell Lung Cancer

Maurie Markman, MD


November 23, 2021

Figure 2. Bone scan showing metastatic lung cancer.

In patients who are resistant to EGFR-TKIs, acquired HER2 amplification is significantly more prevalent (13%) than are de novo alterations (3%). Differentiating de novo HER2 amplification from acquired HER2 amplification may therefore be beneficial.

HER2 mutations are usually mutually exclusive with other oncogenes in NSCLC. In fact, the incidence of HER2 mutations can be as high as 6.7% among patients with EGFR/ALK/ROS1–negative NSCLC and who are negative for EGFR in particular. However, according to the results from the European EUHER2 cohort study, which included 101 patients with HER2-mutant NSCLC, there were coexistent EGFR mutations, ALK translocations, and ROS translocations in five patients, one patient, and one patient, respectively.

The prognostic value of HER2 mutations is not yet clear. Some studies have shown that there are no significant differences in overall survival between patients with wild-type and mutated HER2; others have linked a HER2 mutation to worse survival compared with HER2 wild-type patients, and still others have shown the opposite.

The most common HER2 mutations in lung cancer occur in exon 20.

Learn more about NSCLC pathophysiology.


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