Oncology Central

Distinct pathways to HER2 positivity identified in lung adenocarcinomas

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A study investigating patient samples of lung adenocarcinoma has determined that there are two distinct routes to HER2 activation within the disease – either mutation of the gene or amplification of the gene. The findings of this University of Colorado Cancer Center (CO, USA) and Memorial Sloan Kettering Cancer Center (NY, USA) appeared last week in the Journal of Thoracic Oncology.

Within the study, lung adenocarcinoma samples isolated from 175 patients underwent fluorescence in situ hybridization analysis to evaluate HER2 amplification and sequencing to assess HER2 mutation status. Overall, 3 % of the samples were positive for HER2 amplification and 3 % were positive for HER2 mutation, with no samples being found to have both genetic changes.

“The question we wanted to answer was if these two genetic alterations tend to be found together. The fact that they do not overlap means that we must test lung tumors separately for both amplification and mutation of HER2 or risk missing patients who might benefit from HER2-targeted therapy,” commented Marileila Garcia, University of Colorado Cancer Center investigator.

Similar analysis of the related EGFR gene in non-small-cell lung cancer produced divergent results, indicating that EGFR mutation and amplification were identified together approximately 80 % of the time. “Because of this, a test for amplification is a surrogate test for mutation, and vice versa,” Garcia continued.

As these results imply that HER2 amplification and mutation are distinct, there is a possibility that the number of patients carrying HER2-dependent lung tumors is higher than thought.

In breast cancer, current anti-HER2 therapies in use for the treatment of HER2-postitive tumors include trastuzumab and lapatinib. In the lung cancer setting, some oncologists are choosing to prescribe these and other targeted therapies approved to target HER2-associated breast cancer to patients with HER2-associated lung tumors.

The results of this investigation into HER2 activation could impact these treatment decisions. As Garcia explained: “However, it may be that gene amplification is more susceptible to treatments based not on TKIs but on antibodies.”

She concluded: “Whether the overexpression of HER2 in these lung cancers is due to mutation or to amplification may make help us conceptualize what we now call HER2 lung cancer as two related but distinct diseases.”

Sources: Li BT, Ross DS, Aisner DL et al. HER2 Amplification and HER2 Mutation Are Distinct Molecular Targets in Lung Cancers. J Thorac Oncol. doi: 10.1016/j.jtho.2015.10.025 (2015) [Epub ahead of print]; University of Colorado Cancer Center

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