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Communications to the Editor |

Association Between Epidermal Growth Factor Receptor Mutation and Improved Survival in Never-Smokers With Primary Adenocarcinoma of the Lung FREE TO VIEW

Ozden Altundag, MD; Kadri Altundag, MD; Paolo Morandi, MD; Mehmet Gunduz, MD, PhD
Author and Funding Information

Affiliations: Hacettepe University Faculty of Medicine, Ankara, Turkey,  S. Bortolo General Hospital, Vicenza, Italy,  Okayama University, Okayama, Japan

Correspondence to: Ozden Altundag, MD, 8181 Fannin St, No 728, Houston, TX 77054; e-mail: altundag@sbcglobal.net



Chest. 2005;127(6):2292. doi:10.1378/chest.127.6.2292
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To the Editor:

In the August 2004 issue of CHEST, Nordquist and colleagues1show that never-smokers with primary adenocarcinoma of lung are predominantly female, present at a higher mean age, and have improved survival when compared to current smokers. These findings may indicate that adenocarcinomas occurring in never-smokers may display a distinct natural history. Epidermal growth factor receptor (EGFR) protein overexpression was observed in 32 to 79% of cases of non-small cell lung cancer, and occurred more frequently in small cell lung cancer and bronchioloalveolar carcinoma than adenocarcinoma or large cell carcinomas.2

Retrospective analysis of patients receiving single-agent gefitinib, a tyrosine kinase inhibitor that targets EGFR, showed that responses were more frequent among patients who had never smoked, women, and patients with bronchoalveolar carcinoma or adenocarcinoma with bronchoalveolar features as in the present study.3It has been shown that these dramatic clinical responses in these patients are induced by activating mutations within the EGFR kinase domain,45 which stimulates antiapoptotic pathways.67 In the light of above information and given the fact that chromosomal abnormalities are infrequent in never-smokers, mutations in the EGFR kinase domain may be one of the most important pathogenetic mechanism in this specific group of patients.

Nordquist, LT, Simon, GR, Cantor, A, et al (2004) Improved survival in never-smokers vs current smokers with primary adenocarcinoma of the lung.Chest126,347-351. [CrossRef] [PubMed]
 
Hirsch, FR, Varella-Garcia, M, Bunn, PA, et al Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis.J Clin Oncol2003;21,3798-3807. [CrossRef] [PubMed]
 
Miller, VA, Kris, MG, Shah, N, et al Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small cell lung cancer.J Clin Oncol2004;22,1103-1109. [CrossRef] [PubMed]
 
Paez, JG, Janne, PA, Lee, JC, et al EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.Science2004;304,1497-1500. [CrossRef] [PubMed]
 
Lynch, TJ, Bell, DW, Sordella, R, et al Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.N Engl J Med2004;350,2129-2139. [CrossRef] [PubMed]
 
Sordella, R, Bell, DW, Haber, DA, et al Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways.Science2004;305,1163-1167. [CrossRef] [PubMed]
 
Cappuzzo, F, Magrini, E, Ceresoli, GL, et al Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer.J Natl Cancer Inst2004;96,1133-1141. [CrossRef] [PubMed]
 

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References

Nordquist, LT, Simon, GR, Cantor, A, et al (2004) Improved survival in never-smokers vs current smokers with primary adenocarcinoma of the lung.Chest126,347-351. [CrossRef] [PubMed]
 
Hirsch, FR, Varella-Garcia, M, Bunn, PA, et al Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis.J Clin Oncol2003;21,3798-3807. [CrossRef] [PubMed]
 
Miller, VA, Kris, MG, Shah, N, et al Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small cell lung cancer.J Clin Oncol2004;22,1103-1109. [CrossRef] [PubMed]
 
Paez, JG, Janne, PA, Lee, JC, et al EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.Science2004;304,1497-1500. [CrossRef] [PubMed]
 
Lynch, TJ, Bell, DW, Sordella, R, et al Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.N Engl J Med2004;350,2129-2139. [CrossRef] [PubMed]
 
Sordella, R, Bell, DW, Haber, DA, et al Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways.Science2004;305,1163-1167. [CrossRef] [PubMed]
 
Cappuzzo, F, Magrini, E, Ceresoli, GL, et al Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer.J Natl Cancer Inst2004;96,1133-1141. [CrossRef] [PubMed]
 
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