Large-Scale Study Shows Correlation of EGFR Mutations with Smoking and Men

Researchers from Memorial Sloan Kettering Cancer Center and the Weill Medical School of Cornell University have shown an association of epidermal growth factor receptor (EGFR) mutations among tumor samples from men and those who smoke cigarettes. Traditionally, these two characteristics have not been thought to be associated with EGFR mutations, but are common in never-smokers and women. D’Angelo et al. now state that if only non-smokers and women were genetically tested for harboring an EGFR mutation, 57% of all EGFR mutations would be missed, supporting evidence from previous studies.

Diagram of the epidermal growth factor receptor (EGFR)

EGFR upregulation is associated with lung cancer and many therapeutic approaches that target EGFR have been developed. Gefitinib (Iressa, marketed by AstraZeneca and Teva) and erlotinib (Tarceva, marketed by Roche) are small-molecule tyrosine kinase inhibitors (TKIs) of EGFR. The monoclonal antibody cetuximab (Erbitux marketed by Bristol Myers Squibb) is in clinical trials for a lung cancer indication.

Because the use of targeted therapies such as gefitinib and erlotinib, warrants testing tumors for an EGFR mutation, the study authors recommend testing for all patients with adenocarcinoma of the lung regardless of the clinical characteristics of the tumor. A patient positive for an EGFR mutation may receive one of these daily oral therapies which are generally effective and non-toxic as a first treatment. 

The study examined the frequency of EGFR mutations in smokers and men, determining the frequency of the mutations and their association with smoking status and male sex. 2,142 stage I to stage IV lung tumors were tested for either an EGFR exon 19 deletion or an L858R mutation in exon 21 of the gene. All tumor samples were from patients at Memorial Sloan Kettering Cancer Center from 2002 to 2009. 

15% of tumors from former smokers, 6% of current smokers, and 52% of never smokers harbored the EGFR mutation. EGFR mutations were found in 19% of tumors from men and 25% of tumors from women. EGFR mutations in ever smokers represented 40% of all mutations that were found. The incidence of EGFR mutations decreased with the number of cigarette-smoking years. 

Importantly, the overall survival of men and smokers with EGFR mutations was similar to the survival of traditionally TKI-treated female and never smoker populations. This study supports the recently emerging sentiment that all patients with lung adenocarcinomas should undergo genetic testing for an EGFR mutation, a policy that has been in place at Memorial Sloan Kettering since 2009.