The Wall Street Journal, April 14, 2004; Page D1

Lung-Cancer Rate Jumps in Women

Baffling Increase Comes As New Cases Decline Among Men The Stigma for Nonsmokers

By Amy Dockser Marcus

Lung cancer, a deadly disease that once primarily afflicted men, has reached epidemic proportions among women, according to a new study published today. Lung cancer now kills more women each year than breast and ovarian cancer combined.
The findings, published in the Journal of the American Medical Association, are likely to fuel a shift already under way in the study and treatment of what's traditionally been considered a male smoker's disease.

While the number of new lung cancer cases diagnosed among men has decreased in recent years, diagnoses among women climbed a surprising 60% between 1990 and 2003, the study found. Two of the authors, Jyoti D. Patel and Mark G. Kris, said that, for the first time, more than half of the patients in their lung-cancer clinics are women.

It's not clear why lung cancer may be striking women at a higher-than-expected rate. Some researchers argue that women may metabolize carcinogens differently than men, making them more susceptible to the disease. Others suggest that women don't repair damage done to DNA as effectively as men or that hormonal differences may play a role. Oncologists say these factors may explain why the jump in lung-cancer rates cannot be fully explained by women's smoking patterns alone.

Lung cancer has surpassed breast cancer as the leading cause of cancer in women by nearly 20,000 patients a year. Yet lung cancer still lacks the public constituency, research clout and visible political profile of the breast-cancer community. An estimated 68,500 women will die from lung cancer this year. (The death toll among men is 88,400 but that has slipped 1% from 2000.) But for every lung-cancer death, $1,200 is spent on research on the disease, while more than $11,000 per death is devoted to breast-cancer research, based on National Cancer Institute data. Lung cancer has a five-year survival rate of only 14%.

An estimated 85 to 90% of all lung cancer patients have smoked at some point in their lives. What's startling is that many of those diagnosed today already have kicked the habit, often decades before, or were so-called "social smokers" at some point in their lives and then quit. The other 10% to 15%, about 20,000 new cases every year, have never smoked. Among the people who have never smoked, women appear more likely to get lung cancer than men, the JAMA study says.

Lung cancer victims have long been stigmatized because of the disease's close connection with smoking, and so for people who have never smoked, it is especially shocking when they get sick. Richard N. Barg, whose partner, Nadine Manney, a life-long nonsmoker and vegetarian, died last year at the age of 45 from lung cancer, says that lung-cancer patients "are treated like a modern day class of lepers, ostracized for their supposed character defects and impulse control problems." He says that Ms. Manney was constantly explaining to friends, co-workers, and even doctors who treated her that she never smoked. People with heart disease or diabetes, which are both strongly linked to diet and obesity, are not blamed for their illnesses, Mr. Barg notes.

Craig Norberg-Bohm of Arlington, Mass., whose wife, Vicki, 48, died of lung cancer last month, says he agreed to tell the local newspaper obituary writer the cause of death only if she would add that Ms. Norberg-Bohm had been a nonsmoker. "People were not ready to offer their hearts until learning she was not a smoker," he says. Some families, like that of Wendy D. Wyrick, a 32-year-old from Lexington, Ky., who never smoked and died in 2003 of lung cancer, are starting to create foundations to help raise awareness and change the stigma around the disease.

Many women often feel "betrayed by the system" says Joan Schiller, who heads the lung-cancer program at the University of Wisconsin in Madison. She also has set up the group Women Against Lung Cancer to encourage research into gender differences in the disease and its treatment and encourage more women doctors to enter the field. "They know about breast cancer, but they never heard of lung cancer or thought they'd get it, and when they go to learn more, they find little research, no support and little hope."

Risk For Women

• More women will die this year from lung cancer than breast cancer and ovarian cancer combined.
• Women appear to be more susceptible to genetic damage caused by smoking than men.
• Women who never smoked get lung cancer more often than men who never smoked.

See a list of Web sites with information on women and lung cancer.

The recent findings are fueling more research into how women respond to lung-cancer treatments. Researchers are particularly excited by evidence that women, especially those who have never smoked, appear more likely to respond to new, targeted cancer treatments such as AstraZeneca PLC's Iressa and Tarceva, which is being developed by OSI Pharmaceuticals Inc., Genentech Inc. and Roche Holding AG.

Women who have never smoked -- defined as someone who has smoked fewer than 100 cigarettes in her lifetime -- were once an overlooked group in lung cancer. Their prognosis was considered no different than other lung-cancer patients and, as a group, they were considered too rare to merit closer study. But with emerging data suggesting that they fare better in trials, doctors are starting to take a closer look.

These patients are a "major area of interest," says Roy Herbst, chief of thoracic medical oncology at the M.D. Anderson Cancer Center in Houston. "If we understand what is different about them, it could help us understand the mechanism of lung cancer and lead to better therapies for everyone."

The first major sign that never-smoking women respond differently to treatment than men or former and current smokers emerged last year. That's when researchers at Memorial Sloan-Kettering Cancer Center in New York reported preliminary results from a trial of Iressa. The drug was approved in 2003 in the U.S. for patients with advanced non-small cell lung cancer, the most common form of the disease. The trial results were published last month in the Journal of Clinical Oncology.

According to the study involving 139 patients, tumors in 25% of the women shrank after they used the drug, compared with only 8% of the men in the trial. The results for people who never smoked were also significantly different. Of the patients who never smoked, 36% responded to the drug, while only 7.7% of the current or former smokers did. The researchers hypothesized that because tumors in never-smokers appear to be less genetically complex than those in former and current smokers, they may arise through mutations in only one or a small number of critical cellular pathways, making it potentially easier to study what goes wrong. If these pathways can then be identified, they may lead to the development of additional treatments.

Early results in a trial with Tarceva suggest that people who never smoked do better with this treatment as well. M.D. Anderson and Vanderbilt University Cancer Center in Nashville are running a trial of Genentech's cancer drug Avastin and Tarceva.

These changes are something Barbara Parisi, 54, has advocated for since being diagnosed nearly five years ago with lung cancer. A runner and life-long nonsmoker, she was shocked when a routine chest X-ray turned up the disease. When she looked around for support groups near her Wall, N.J., home, she says she found smoking cessation ones but no groups that were specifically for lung-cancer patients.

She got involved in patient advocacy and participated in the first annual Thomas G. Labrecque Classic last year -- a four-mile road race in New York that raises money for lung-cancer research. It was established in memory of the never-smoking former bank chairman who died of the disease. "One reason lung cancer has lagged behind other cancers," she says, "is the fact that so few of us survive."

Lung Cancer Resources
The following Web sites have more information about women and lung cancer.

Organization Site Comment
Alliance for Lung Cancer Advocacy, Support, Education Patient support, developing a special section targeted to women
American Cancer Society Information on lung cancer, support groups
It's Time To Focus On Lung Cancer Funded by Bristol-Myers Squibb, the site lists clinical trials, treatment and prevention information
Joan's Legacy Funds research in the disease, special interest in lung cancer in people who have never smoked
LungCancerOnline Foundation Information about medical treatment and support
Women Against Lung Cancer Supports research into gender differences in diagnosing and treating lung cancer





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