Different Targeted Therapies Needed for HER2 Alterations in Lung Cancer

Researchers find the amplification and mutation of human epidermal growth factor receptor 2 should be treated separately.

Researchers have found that the amplification and mutation of human epidermal growth factor receptor 2 (HER2) in lung cancer are not equal and should be tested and treated separately.

A study published in the Journal of Thoracic Oncology noted 2 specific causes of HER2 activation in lung cancer: gene mutation and gene amplification. Researchers found that in patient samples of lung adenocarcinoma, 3% had HER2 amplification, while an additional 3% have HER2 mutation.

None of the samples had both mutation and amplification. These findings suggest different targeted therapies should be used to fight diseases that are related, but potentially distinct.

"The question we wanted to answer was if these two genetic alterations tend to be found together,” said investigator Marileila Garcia, PhD. “The fact that they are not overlapped 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."

The results are in opposition of previous findings with a closely related gene, EGFR, which can also be called HER1 and belongs to the same family. EGFR mutations and amplifications are found together approximately 80% of the time.

"Because of this, a test for amplification is a surrogate test for mutation, and vice versa," Garcia said.

They study also goes along with the exploration of HER2 in breast cancer. Since about 20% of breast cancers have HER2 amplification, it makes the tumors susceptible to treatment with anti-HER2 therapies like trastuzumab and lapatinib. These therapies [an antibody and a tyrosine kinase inhibitors] reduce a target gene from being able to manufacture the protein it encodes.

"However, it may be that gene amplification is more susceptible to treatments based not on TKIs but on antibodies," Garcia said. "Whether the overexpression of HER2 in these lung cancers is due to mutation or to amplification may help us conceptualize what we now call HER2 lung cancer as two related but distinct diseases.”