Lung cancer rates high for women nonsmokers

Researchers are moving beyond chemotherapy to study the biology of lung cancer to defeat this killer.

By Susan J. Landers — Posted Oct. 15, 2007

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A sizeable number of lung cancers are diagnosed among women who never used tobacco, according to new findings. Two recent examples illustrate this point. The disease caused the death this year of opera legend Beverly Sills and last year of Dana Reeve, wife of actor Christopher Reeve. Neither was ever a smoker.

Although most lung cancers are the result of smoking, one-quarter of cases worldwide, accounting for 300,000 deaths, are not attributable to this cause, says a study in the October Nature Reviews Cancer. And more of these cases occur among women than men.

Yet the disease is not always suspected among nonsmokers, and their symptoms can be attributed instead to other conditions, said researchers and clinicians who spoke at a Sept. 17 Capitol Hill briefing sponsored by the Society for Women's Health Research.

Joan Schiller, MD, deputy director of Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center in Dallas, recounted the following experience: By the time she saw one particular patient, the woman had been coughing for a year. During that period, she had been treated for asthma, but she actually had lung cancer.

Yet, early referrals can make a difference, because there has been slight progress in treatment, Dr. Schiller said. Chemotherapy with any of the four regimens in use does result in small improvements in survival rates. "[But] I think we have come to the end of our progress with chemotherapy," she added. "We need to move on to therapies based on the biology of lung cancer."

Promising research areas

One therapy now in development at Dr. Schiller's institution would subvert the process used by cancer cells to grow faster than normal cells.

Telomeres, which are bits of DNA that cap the end of all mammalian chromosomes, grow shorter as healthy cells divide -- eventually becoming so short that the cell dies. But cancer cells contain an enzyme, called telomerase, which adds DNA back onto the telomeres to enable the cells to go on dividing. Drugs now in development will inhibit the production of telomerase, Dr. Schiller said, and this line of research could benefit all cancer treatments, not just lung cancer.

Research also continues on drugs to block the formation of the new blood vessels required for tumor growth, known as angiogenesis. Clinical trials are under way on drugs that block the hormone -- vascular endothelial growth factor -- which causes this process. One such randomized trial in lung cancer patients showed increased survival rates, Dr. Schiller said. "Again, we may have a small step forward in terms of lung cancer."

Vaccine development is another continuing research area, she said. Its aim is to teach the patient's immune system to fight cancer. Although such research has been ongoing for decades, in the last five or 10 years gains have been made in developing more tumor-specific and easier-to-manufacture vaccines.

Personalized medicine is the way of the future, Dr. Schiller said.

Investigators also are building on research related to other cancers, particularly breast cancer, said Jill Siegfried, PhD, professor and vice chair of pharmacology at the University of Pittsburgh School of Medicine. Estrogen, which is known to enhance the growth of pre-cancerous and cancerous breast cells, is suspected of playing a similar role in lung cancer.

Researchers also determined that pre-menopausal women with lung cancer, those with the highest level of estrogen, have the worst survival rate of any group, Dr. Siegfried said. This concept may play a role in the fact that women who have never smoked have twice the risk of developing lung cancer as do men -- although men also have some circulatory levels of estrogen that increase with older age, she said, and the hormone is found in their tumors as well.

With this connection in mind, Dr. Siegfried's lab is looking at anti-estrogen treatments and their effect on lung tumors. The thought is that aromatase inhibitors, developed primarily for fighting breast cancer, might have a place in lung cancer treatment.

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