Clinicopathologic and Molecular Subtyping of EGFR Mutation-Letter.

Abstract

Jung and colleagues found that among patients with EGFR-mutated non–small cell lung cancer (NSCLC), patients with tumor molecular profiles that also demonstrated a TP53 mutation had “poor recurrence-free survival (RFS) independent of pStage II or IIIA” and concluded that a novel adjuvant treatment strategy “needs to be investigated” for these patients. Thus, their report suggests that the dual biomarker EGFR/TP53 mutation is a predictor of poor RFS (1).There are two groups of patients with tumors showing the dual biomarker EGFR/TP53 mutations. The authors did not discuss how the RFS of those with the dual biomarker EGFR/TP53 mutations compared between patients who were confirmed to have Li Fraumeni syndrome (LFS) and patients who did not have LFS.Roughly 15% of NSCLCs have EGFR mutations and Labbe reported that dual TP53/EGFR mutations were found in 43 of 105 (41%) patients (2). Skoulidis and Heymach reviewed the results from several studies and estimated that dual TP53/EGFR mutations occur in 60% of NSCLCs (3).Patients with LFS and NSCLC, typically have EGFR-mutated NSCLC, including one study showing that 26 of 30 patients with LFS had EGFR-mutated NSCLC (4, 5). Benusiglio and colleagues concluded “for unknown reasons, the majority of Li Fraumeni-associated lung adenocarcinomas harbor EGFR somatic activating variants.” Regarding referral to genetics clinics for LFS exploration they suggested, “In our opinion, too little prominence is given to lung adenocarcinoma.” (4).Because 2%–7% of NSCLCs are thought to be LFS related, if germline testing (GT) is recommended for these 7.5% of patients with NSCLC, it can be estimated that half will be confirmed to have LFS (4).Jung and colleagues nicely showed that dual TP53/EGFR mutations predicted poor RFS. GT should be considered in patients with this dual biomarker to diagnose those patients with LFS, as there are recommended measures to diagnose early LFS-associated cancers in those patients and affected family members. Future reports might compare the RFS between those with dual TP53/EGFR mutations and LFS and the RFS among those with dual EGFR/TP53 mutations who do not have LFS to establish whether LFS is a more or less accurate predictor of RFS among patients whose tumors demonstrate the dual biomarker EGFR/TP53 mutations.See the Response, p. 687S. Sorscher reports other support from Invitae, Corp outside the submitted work. No other disclosures were reported.