Molecular landscape of HER2-mutated non-small cell lung cancer in Northeastern Brazil: Clinical, histopathological, and genomic insights

PMCID: PMC12173199

PMID: 40526089

DOI: 10.18632/oncotarget.28737

Journal: Oncotarget

Publication Date: 2025

Authors: Nogueira CD, Frota S, Chaves HL, de Sousa JC, Veloso GD, et al.

Key Points

• HER2 mutations were identified in 4.9% of NSCLC cases, with exon 20 insertions being the most prevalent
• The DESTINY-Lung01 Trial demonstrated a 55% response rate to trastuzumab deruxtecan in HER2-mutant NSCLC patients
• Comprehensive molecular profiling is crucial for identifying potential targeted therapy candidates in lung cancer

Summary

This retrospective study investigated HER2 genomic alterations in non-small cell lung cancer (NSCLC) among 13 patients from Northeastern Brazil, providing critical insights into the molecular landscape of an underrepresented population. The cohort demonstrated significant heterogeneity, with HER2 mutations predominantly involving exon 20 insertions (A775_G776insYVMA), and a median patient age of 58 years, with a slight female predominance. The research highlighted the complex genomic profile of HER2-mutated lung cancers, revealing frequent co-mutations in TP53, KRAS, and STK11, and emphasizing the need for comprehensive molecular profiling.

The study's findings have important clinical implications, particularly regarding targeted therapy potential. While only one patient received trastuzumab deruxtecan, the results align with emerging evidence from global trials suggesting that HER2 mutations represent actionable biomarkers in NSCLC. The molecular diversity observed underscores the importance of precision medicine approaches, with HER2 mutation testing potentially guiding treatment strategies in lung cancer management.