Correspondence

Lung Cancer

N Engl J Med 2009; 360:87-88January 1, 2009

Article

To the Editor:

In the introductory remarks of their article, Herbst et al. (Sept. 25 issue)1 note, “Smoking causes all types of lung cancer but is most strongly linked with small-cell lung cancer and squamous-cell carcinoma.” In the legend to Figure 1, they also note, “Most tumors that are not related to smoking are adenocarcinomas and develop in the peripheral airways.” This statement almost echoes Kreyberg's observation2 in 1962 regarding the “slight, if any” relationship between cigarette smoking and adenocarcinoma of the lung.

In the past 47 years, adenocarcinoma has become the predominant type of cancer cell in male smokers as well as female smokers. In the period from 1959 to 1991, the incidence of adenocarcinoma increased dramatically, by a factor of 10 in men and by a factor of 17 in women.3

The dramatic rise of adenocarcinoma of the lung for the most part has occurred “in the discolored smoking-related lungs” and not in the bright pink lungs that have not been exposed to smoke, as depicted in Figure 1 of their article.

James H. Lutschg, M.D.
1061 Magnolia Wood Ave., Baton Rouge, LA 70808

3 References

1. 1

   Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J Med 2008;359:1367-1380
   Full Text | Web of Science | Medline

2. 2

   Kreyberg L. Histological lung cancer types: a morphological and biological correlation. Acta Pathol Microbiol Scand Suppl 1962;157:1-92
   Medline

3. 3

   Thun MJ, Lally CA, Flannery JT, Calle EE, Flanders WD, Heath CW Jr. Cigarette smoking and changes in the histopathology of lung cancer. J Natl Cancer Inst 1997;89:1580-1586
   CrossRef | Web of Science | Medline

Author/Editor Response

Lutschg is correct that adenocarcinoma is the predominant cell type in all patients with lung cancer, including patients who are current and former smokers and patients who have never smoked; this is the case with patients at the University of Texas M.D. Anderson Cancer Center (Spitz M, Merriman K: personal communication).1,2 We emphasized the increase in the incidence of adenocarcinoma among persons who have never smoked (the pink lungs in Fig. 1 of our article), since the disease in this subgroup of patients has a different biology and molecular origin than it does in patients who have smoked.3 The unique genetic changes detected more frequently in persons who have never smoked than in current or former smokers with lung cancer have enabled the development of more effective therapy for these patients.4 Ultimately, a more complete understanding of the genetic profiles of all lung cancers (smoking-related or not) will be needed to better define the pathogenesis, prognosis, and likelihood of a therapeutic response in individual cases of lung cancer, as we emphasized in our review article.

Roy S. Herbst, M.D., Ph.D.
John V. Heymach, M.D., Ph.D.
Scott M. Lippman, M.D.
University of Texas M.D. Anderson Cancer Center, Houston, TX 77030
slippman@mdanderson.org

4 References

1. 1

   Kachroo S, Tong L, Spitz MR, et al. Trends in prevalence of prognostic factors and survival in lung cancer patients from 1985 to 2004 at a tertiary care center. Cancer Detect Prev 2008;32:101-108
   CrossRef | Web of Science | Medline

2. 2

   Muscat JE, Wynder EL. Lung cancer pathology in smokers, ex-smokers and never smokers. Cancer Lett 1995;88:1-5
   CrossRef | Web of Science | Medline

3. 3

   Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers -- a different disease. Nat Rev Cancer 2007;7:778-790
   CrossRef | Web of Science | Medline

4. 4

   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 Med 2004;350:2129-2139
   Full Text | Web of Science | Medline