Germline EGFR mutations and familial lung cancer - Lung Cancer Research Foundation

The good news
Different aspects of lung cancer risk are still poorly understood. This is particularly true of the hereditary risk of developing lung cancer. The presence of the epidermal growth factor receptor (EGFR) mutation T790 in germline cells (cells that can pass on genetic information) can be associated with a hereditary form of lung cancer.

Why it’s important
The INHERIT trial studied individuals and their relatives with and without lung cancer evaluating for the EGFR T790 mutation in germline cells (Journal of Clinical Oncology, Volume 41, pages 5274-5284, 2023). They found that 55% of the participants who had this germline mutation were affected by lung cancer usually by age 60. Most of the lung cancers were EGFR mutation positive in somatic (non-inherited) cancer cells. These patients responded well to Osimertinib. The risk of developing lung cancer if a germline mutation was present was variable, which means that having the T790 mutation did not necessarily result in the development of lung cancer. It was also found that patients who did not have lung cancer frequently had lung nodules. These abnormalities would have to be followed for potential development of lung cancer.

What it means for patients
This is one of the first studies describing a pattern of inheritance in lung cancer. This may have future implications for individuals who carry this genetic abnormality regarding screening for early detection of lung cancer. This will be especially important for patients who are never smokers.

What to watch for
This is just the beginning with respect to understanding the hereditary risk for developing lung cancer. In the future look for similar studies that will help researchers define individuals at risk for lung cancer.