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Lung Cancer in People Who Have Never Smoked

With fewer people smoking in the US, why are lung cancer rates among people who have never smoked on the rise? “While it is true that smoking tobacco is the top risk factor for lung cancer, a substantial number of people receive a diagnosis despite having never smoked,” said Margie Clapper PhD, deputy scientific director and co-leader of the Cancer Prevention and Control Program at Fox Chase.


An estimated 20 percent of people who get lung cancer have never smoked.


Why would people who have never smoked get lung cancer?

“It is common for ‘never smokers’ to be puzzled as to why they got lung cancer,” said Joseph Treat, MD, professor in the Department of Hematology/Oncology at Fox Chase. “Many are surprised to find out that 1 in 5 people who get lung cancer have never smoked. My patients are often younger women who have not smoked and tried to do everything right. Some may feel angry. They don’t expect a diagnosis of lung cancer. I make sure they know that they are not alone, and encourage them to use their feelings to help push through the disease.”

Environmental factors such as workplace exposure to asbestos or cancer-causing agents, air pollution, or even radon gas trapped indoors can play a role for some never smokers, but few can point to a specific cause. Having family members who have never smoked but had lung cancer can be a red flag, but this is not very common. It is not yet clear why so many people who have few known risk factors get lung cancer.

Never Smokers Get A Certain Type of Lung Cancer

Most lung cancers in never smokers are adenocarcinomas, a type of non-small cell lung cancer. It would be very unusual for a never smoker to have squamous or small cell lung cancers.

Early Diagnosis Is Optimal

Some (but not all) studies suggest that overall survival is better in non-smokers, particularly if they are diagnosed early. Lung cancer in people who do not smoke is often diagnosed at a late stage, however, especially if symptoms are subtle. Early symptoms may be incorrectly attributed to a respiratory infection or to allergies—lung cancer may not be suspected.

“Screening helps, but the American Cancer Society and other guidelines focus on smoking status and age, which means younger never smokers are not routinely screened,” Treat noted.

New Approaches to Treatment for Never Smokers

“At Fox Chase our highly experienced multi-specialty team of surgeons, medical, and radiation oncologists, and pulmonologists work exclusively with lung cancer patients,” Treat said. “We have a new clinic that specifically addresses the needs of people who have never smoked. This is important because they need different treatments. Many have certain mutations, such as EGFR – a mutation often seen in never smokers that sits on the cell surface and can tell cancer cells to grow and divide – that tend to be responsive to particular treatments but not to others.” Immunotherapy, an exciting breakthrough in cancer treatment, is often not as effective in never smokers with the EGFR mutation, for example, as compared to in smokers without the mutation.

“Patients come to me excited about immunotherapy, but about 12 percent of my patients who have never smoked have the EGFR mutation,” Treat said. “In Asia, 30 to 45 percent of patients may have the EGFR mutation. Getting immunotherapy to work in these patients is a pressing issue.”


Fox Chase has a new, dedicated lung cancer clinic for never smokers.


“We take a three-pronged approach at Fox Chase,” Treat said. “We treat patients in the clinic, we run clinical trials, and we do basic research. We are currently working to design a clinical trial to understand how to overcome the resistance to immunotherapy that develops in never smokers.”

Researchers at Fox Chase are also exploring why lung cancer is more common among women never smokers than among their male counterparts. A team of researchers, led by lead author Jing Peng, PhD, a research associate at Fox Chase, found that human lungs can metabolize the hormone estrogen to form a carcinogenic agent. They discovered that production of the carcinogenic estrogen metabolite varies with race, ethnicity, sex, and smoking status.

“Women had higher levels of the estrogen metabolite in their lungs than men, as expected,” Peng said. “Chinese-American women produced more of the carcinogenic estrogen metabolite than non-Hispanic white women, which makes sense, as Chinese never-smoking women have much higher rates of lung cancer than never-smoking European and Caucasian women,” Peng said.

“This is just one foundational approach we are looking into at Fox Chase,” Treat added. “We have good treatment options for never smokers who develop lung cancer and, with our new lung cancer clinic for never smokers, we plan to develop additional strategies.”

Learn more about the never smokers clinic at Fox Chase Cancer Center.