The cancers associated with germline EGFR T790M mutations share several similar features with lung cancers containing sporadic EGFR mutations, such as a predominance for adenocarcinoma histology, female gender, and never-smoking status. However, a difference with lung cancers having sporadic EGFR mutations is a predominance for white ethnicity (compared with East Asian).
In the second study, Helena A. Yu, MD, of Memorial Sloan-Kettering Cancer Center, New York, NY, and colleagues identified the germline EGFR T790M mutation in a 44-year-old female never-smoker. The researchers subsequently tested eight family members and detected the mutation in two additional members (mother and daughter), also never-smokers. Metastatic lung cancer developed in the proband's mother, and the radiographic appearance of the lung cancer was the same for both women, with bilateral ground-glass opacities and pulmonary nodules.
"Germline EGFR T790M mutations are present in approximately 50% of all patients with baseline EGFR T790M identified in their tumor specimens before treatment," says Dr. Yu, also an IASLC member. "In our practice, we recommend that all patients with baseline EGFR T790M identified in their lung tumor tissue be referred to clinical genetics to discuss EGFR T790M germline testing. Carriers of this mutation need to be prospectively studied to better understand the clinical implications of this germline mutation.
The presence of a germline EGFR T790M mutation also predicts for resistance to standard tyrosine kinase inhibitors (TKIs), which adds complexity to treatment. Until newer third- and fourth-generation TKIs designed to overcome T790M-mediated resistance become available, standard chemotherapy may be the preferred first-line therapy option in the absence of another known or suspected molecular target.
|Contact: Kristin Richeimer|
International Association for the Study of Lung Cancer