Lung Cancer

September 16, 2011

Lung cancer, a largely incurable disease, remains the leading cause of cancer deaths among women each year in the United States, exceeding annual breast cancer mortality in women and accounting for 12% of all new female cancer cases (Table 1). Although lung cancer has always been and continues to be more prevalent in men than in women, lung cancer mortality patterns now reveal that the rate of rise of such cancer deaths among men has slowed and begun to decline since 1990, whereas in women it has continued to rise. Several studies suggest that women are more susceptible than men to lung cancer and to conditions, like chronic obstructive pulmonary disease, that predispose to this cancer; hence the question has been raised as to whether lung cancer is a different disease in women than in men.

Table 1. Estimated cancer deaths from the 10 leading sites in males and females: All ages, 1999
Females % Males %
Lung and bronchus 25 Lung and bronchus 31
Breast 16 Prostate 13
Colon and rectum 11 Colon and rectum 10
Pancreas 5 Pancreas 5
Ovary 5 Non-Hodgkin’s lymphoma 5
Non-Hodgkin’s lymphoma 5 Leukemia 4
Leukemia 4 Esophagus 3
Uterine corpus 2 Liver/Intrahepatic Bile Duct 3
Brain and other nervous system 2 Urinary bladder 3
Stomach 2* Stomach 3
Multiple myeloma 2* All other sites 20
Other sites 21
Note: Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.

*These two cancers received a ranking of 10 (they have the same number of deaths and contribute to the same percentage).

Source: Landis, S. H., Murray, T., Bolden, S., et al. Cancer Statistics. CA Cancer J Clin. 1999, 49, 8-31.

Overall smoking remains the most important risk factor for the development of lung cancer in both women and men, and the smoking trends have changed in women over the years to parallel an increase in the number of female lung cancer cases. “Although there has been a large decline from the peak female smoking rate of 34.2% seen in 1965, smoking among teenage girls has increased dramatically over the past decade. Among high school students, cigarette use (defined as at least one cigarette in the past 30 days) has increased from 21% in the 1980s to about 35% of both boys and girls in 1997″ (Siegfried, 2001). In 2001, the U.S. Surgeon General issued a new report, Women and Smoking, in which the 600% increase since 1950 in female lung cancer death rate was described as “a fullblown epidemic,” wherein smoking is now the leading cause of preventable death and disease in women.

Although research has been unable to determine whether the association between smoking and lung cancer is stronger for women than for men, studies now suggest that lung cancer induced by smoking, environmental factors, and the like follows a different pattern in women than in men; hence, there might be important differences between women and men that influence lung cancer risk. Reports have indicated that women smokers have a greater risk of developing small-cell lung carcinoma (smaller risk of squamous cell carcinoma) than men smokers (who have a similar risk for small-cell carcinoma and squamous cell carcinoma). In addition, studies report that for a given amount of smoking, women may be up to twice as likely to develop lung cancer as men, and nonsmokers who develop lung cancer are two and a half times more likely to be female than male.

Adenocarcinoma of the lung, more common among nonsmokers than smokers, is found predominantly in women, whereas men are more likely to be diagnosed with squamous cell carcinoma. This suggests that women may be more susceptible to adverse effects of tobacco due, in part, to female hormones, namely, estrogenmediated effects. Taioli and Wynder found that early age at menopause (40 years or younger) is associated with a reduced risk of adenocarcinoma of the lung, whereas the use of estrogen-replacement therapy is associated with a higher risk of lung adenocarcinoma (Figure 1). In addition, the study revealed a positive interaction between estrogen-replacement therapy, smoking, and the development of adenocarcinoma of the lung. Estrogens may have a role in directly causing cancer (direct-acting carcinogens) and may enhance the metabolic activity of cigarette smoke cancer-causing components (carcinogens). Estrogen receptors have been reported in lung tumors when studied using special diagnostic microscopic stains, and lung tumors from women are more likely to express estrogen receptors than those from men.

Figure 1. More males than females died over an 11 year period from lung cancer. Note the steadily increasing deaths in women over the same time period.

Women may not only be more susceptible to the adverse effects of tobacco but also more prone to lung diseases that predispose to lung cancer. A history of pneumonia (especially in childhood), tuberculosis, asthma, chronic bronchitis, and chronic obstructive pulmonary disease/emphysema have all been associated with a higher risk of lung cancer in nonsmokers, mainly in studies of women. Among these diseases, chronic obstructive pulmonary disease affects more nonsmoking women than men and increases their lung cancer risk; therefore, speculation as to estrogen involvement in this predisposition and further research behind this higher female susceptibility to lung disease may provide valuable insight as to the onset of lung cancer in women and more effective treatment.

Determination of the mechanisms behind various forms of nonsmoking and smoking-related lung cancer in women will enable more effective treatment options. Since about 80% of lung cancer cases are attributable to smoking, it is clear that smoking rates must be reduced to zero to halt the lung cancer epidemic for both men and women. Lung cancer cases that cannot be prevented must be diagnosed at as early a stage as possible since survival rates are highest for patients who present with early-stage disease. Staging of lung cancer (see Table 2) takes into account location of the tumor, histology, lymph node involvement, and metastasis (spread to various organs). Chest radiograph screening to detect early forms of lung cancer may provide a useful method, but gender differences must be considered when examining for lung cancer risk. Women were only included in 2 of the 11 prospective studies of lung cancer screening to date, and therefore further investigation is warranted to adequately study the role of lung cancer screening for women. In addition, preclinical and clinical trials should address gender as a specific research variable to improve and focus lung cancer therapy. The suggested role of estrogens in lung adenocarcinoma development in many female nonsmokers and the increased susceptibility in women to the carcinogenic effects of cigarette smoke warrant further study to hopefully better target screening studies and develop more effective therapy against lung cancer in women.

Table 2. Staging lung cancer: TNM subsets by stage
Stage 0 Carcinoma in situ  
Stage 1A T1 N0 M0 T1 = tumor £ 3.0 cm, surrounded by lung tissue; no lymph node involvement; no evidence of invasion
Stage 1B T2 N0 M0 T2 = tumor a 3.0 cm, or tumor of any size that invades visceral pleura or associated atelectasis (collapse of lung alveoli)
Stage IIA T1 N1 M0 T1 tumor with lymph node involvement in peribronchial or ipsilateral hilar region, or both
Stage IIB T2 N1 M0 T2 tumor with lymph node involvement
T3 N0 M0 T3 = tumor of any size with direct extension into the chest wall, diaphragm, etc. without involving the heart, great vessels, trachea, esophagus, etc.; N0 = no lymph node involvement
Stage IIIA T3 N1 M0 T3 tumor with lymph node involvement
T1 N2 M0, T2 N2 M0 T3 N2 M0 T1 or T2 tumor; N2 = metastasis to ipsilateral mediastinal lymph nodes and subcarinal lymph nodes
Stage IV Any T, Any N, M1 M1 = distant metastasis present
Note: T = primary tumor; N = lymph node involvement; M = distant metastasis. Adapted from Mountain, Libshitz, and Hermes (1999).

SEE ALSO: Cancer, Hormone replacement therapy, Lung disease, Smoking.

Suggested Reading

  • Healey Baldini, E., & Strauss, G. M. (1997). Women and lung cancer: Waiting to exhale. Chest, 112 (Suppl.), 229S-234S.
  • Mountain, C. F., Libshitz, H. I., & Hermes, K. E. (1999). Lung cancer: A handbook for staging, imaging, and lymph node classification. Houston, TX: Charles P. Young Company.
  • Siegfried, J. M. (2001). Women and lung cancer: Does oestrogen play a role? The Lancet Oncology, 2, 506—513.

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