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Lung cancer rare in nonsmokers

Genetic mutation, environment may be factors in such cases

By Peggy Peck
MedPageToday.com Managing Editor

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Dana Reeve, seen at a 2004 event, died of lung cancer Monday at age 44. The activist said she never smoked.

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(MedPage Today) -- Although Dana Reeve said that she had never smoked, most lung cancers are associated with smoking or exposure to secondhand smoke.

Researchers at Memorial Sloan-Kettering Cancer Center in New York reported last year that they believe a genetic mutation causes cancer in nonsmokers.

That mutation, they reported in the Proceedings of the National Academy of Science, suggests that nonsmokers have a distinct form of lung cancer, according to Dr. William Pao and colleagues.

Reeve, the widow of the late actor Christopher Reeve, died Monday night at age 44, according to the Christopher Reeve Foundation.

Dana Reeve was chairwoman of the foundation set up by her husband.

Although smoking is the leading cause of lung cancer in women, the percentage is less than it is for men.

In 1999, smoking was responsible for about 87 percent of cases of lung cancer -- 90 percent in men and 79 percent in women, according to estimates by the American Cancer Society, National Cancer Institute and Centers for Disease Control and Prevention.

Studies at the universities of Maryland and Michigan, both published last year in the journal Chest, reported that there was a greater percentage of lung cancer among women younger than 50, smokers or nonsmokers, than among men.

In the Michigan study, women accounted for 40.9 percent of patients younger than 50 and for 35.4 percent older than 50.

Besides a genetic mutation, other factors associated with lung cancer include exposure to asbestos or fine airborne particulates.

The Sloan-Kettering researchers said the mutation occurs in the epidermal growth factor -- a protein involved in cell growth -- and is more common in nonsmokers with lung cancer than in smokers.

The nonsmokers in Pao's study had what is called adenocarcinoma non-small cell lung cancer, or NSCLC.

Two drugs target the mutation -- Tarceva and Iressa -- and clinical trials of the drugs reported better response rates for nonsmokers.

Tarceva has been shown to increase survival, but Iressa has not demonstrated a survival benefit, which led the Food and Drug Administration to issue a label change that limits use of the drug.

Patients with NSCLC diagnosed at its earliest stage, when the tumor is confined to the lung (Stage 1), have the best prognosis, although survival depends on tumor type and the overall health of the patient.

Stage 1 is divided into 1A and 1B, depending upon the size of the tumor. In most cases, the tumor is removed by surgery, but patients who are not candidates for surgery are treated with radiation. Surgical removal is followed by chemotherapy, usually with tumor-killing drugs.

Patients with cancers that have spread locally or regionally are candidates for a variety of therapies. If the tumor can be surgically removed, patients may undergo either pre-operative or postoperative chemotherapy or chemoradiation therapy.

Patients with Stage 1 cancers whose tumors are too large to be surgically removed are treated with a combination of chemotherapy and radiation therapy.

Reeve revealed that she had lung cancer in August, less than a year after her husband's death.

Christopher Reeve died in October 2004. Nine years earlier, he was paralyzed after suffering a spinal cord injury in a horseback riding accident. The actor spent the rest of his life as an activist for the disabled and a champion for research.

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