Chest
Volume 128, Issue 1, July 2005, Pages 370-381
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Lung Cancer in Women: Emerging Differences in Epidemiology, Biology, and Therapy

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Lung cancer is the major cause of cancer-related death in both men and women in the United States. Emerging evidence indicates that there are differences in the pathogenesis and possibly increased susceptibility to lung cancer in women. In addition, considerable data support small, but important differences favoring women in terms of response to therapy and long-term survival after the diagnosis of lung cancer, regardless of histology or stage. These differences in both biology and outcome will be important considerations in the design of future trials of screening and therapy for lung cancer.

Section snippets

Smoking

Smoking is the overwhelming cause for lung cancer in both men and women; 85 to 90% of patients with lung cancer are current or former tobacco smokers. Smokers are 22 times more likely to die from lung cancer than nonsmokers.3 Although smoking is a risk factor for all histologic types of lung cancer, the association is stronger for small cell, squamous cell, and large cell carcinoma than for adenocarcinoma.

Women began smoking in significant numbers in the 1940s, with a peak incidence in the

Pathobiology

The development of lung cancer is the end result of a complex interplay of factors including carcinogen exposure, metabolism, and genetics. Tobacco smoke, recognized to be the foremost risk factor for lung cancer, contains more than a hundred diverse mutagens and carcinogens, including polycyclic aromatic hydrocarbons, N-nitro amines, and aromatic amines. The initiating activity remains for an extended period after the cessation of smoking.

Two classes of enzymes play a crucial role in the

Molecular Abnormalities

Many genetic and epigenetic alterations of tumor suppressor genes have been demonstrated in lung cancer. The most frequent genetic alterations found are in p53 (in 90% of small cell lung cancers [SCLCs] 40 to 70% of non-small cell lung cancers [NSCLCs]) and in oncogenes such as K-ras. The p53 pathway has long been recognized as playing a key role in cell cycle regulation by causing arrest in both the G1 and G2 phases in cell division in response to DNA damage. This arrest allows for DNA repair

Therapeutic Implications

Although the incidence of lung cancer is higher in women than in men and continues to rise, women have superior responses to therapy. This appears to be true regardless of stage, therapeutic modality, or histology (Tables 2, 3). In the mid-1970s, Edmonson et al75 noted that “survival was better for ambulatory patients and women survived longer than men” regarding outcome of chemotherapy-treated patients with adenocarcinoma or inoperable small cell carcinoma of the lung. The Surveillance,

Smoking Cessation

Smoking is the most predominant risk factor for all the different tissue types of lung cancer. It has long been known that the risk of lung cancer declines after smoking cessation. The risk after a patient stops smoking appears to be related to the level of consumption. In those persons who have smoked 1 to 20 cigarettes per day, the risk decreases to 1.6 at 15 years after smoking cessation. In those who had smoked > 21 cigarettes per day, the risk for lung cancer at 15 years after quitting

Conclusion and Outlook

Lung cancer is the major cause of cancer-related death in women. It is possible that women are inherently more susceptible to lung cancer, although that issue is far from settled. There are, however, very clear differences in the biology, natural history, and response to therapy between men and women with this disease. An emerging literature provides a biological basis for these differences, but this understanding is quite tentative. Most of the literature on this topic is retrospective and

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    Learning Objectives: 1. Identify major differences between men and women diagnosed with lung cancer as it relates to biological and natural history as this disease progresses. 2. State the different responses to the therapeutic interventions between men and women diagnosed with lung cancer.

    Dr. Edelman has indicated to the ACCP that he has not received anything of value, either directly or indirectly, from a commercial or other party related directly or indirectly to the subject of this article submission.

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