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Kathy Griffin's Early-Stage Lung Cancer

— A closer look at diagnosis in "never-smokers"

MedpageToday
A photo of Kathy Griffin performing on stage.

Earlier this month, comedian and actress Kathy Griffin to announce that she would be undergoing surgery for early-stage lung cancer.

"I've got to tell you guys something. I have cancer. I'm about to go into surgery to have half of my left lung removed. Yes, I have lung cancer even though I've never smoked! The doctors are very optimistic as it is stage one and contained to my left lung. Hopefully no chemo or radiation after this and I should have normal function with my breathing. I should be up and running around as usual in a month or less. It's been a helluva 4 years, trying to get back to work, making you guys laugh, and entertaining you, but I'm gonna be just fine," she wrote.

In a recent Nightline interview with Juju Chang, how difficult the past few years have been for her.

In 2017, the controversial comedienne was widely panned after posting a picture of herself holding a model of then-President Trump's bloody, decapitated head. Griffin later took down the image, admitting she had gone too far and asking for forgiveness. Despite this, she was dropped by many of her sponsors, fired from CNN's New Year's Eve broadcast, and her remaining tour dates were canceled.

Griffin said that her home phone number and address were released, and she was harassed by Trump supporters. In addition, her family received death threats, including her mother, who was living in a nursing home, and her sister, who was dying of esophageal cancer.

Griffin found it nearly impossible to find work. She said that she was told, "It's over ... Go to Europe for 5 years ... You've shamed our industry." The stress caused her to become addicted to prescription pain medication. In June 2020, Griffin tried to take her own life by taking over 100 pills. She fell down some stairs, injuring herself, and eventually was able to text her doctor. She told him what was going on, and she was taken to the hospital.

The unsuccessful attempt was a wake-up call. She went into rehab and underwent a withdrawal that she described as "brutal." She credits Alcoholics Anonymous and their sober coaches for saving her life.

The day after her Nightline interview, Griffin underwent her surgery, which went well, she said. She later : "To be honest, this cancer surgery was a little more than I had anticipated. Tonight will be my first night without any narcotic pain killers [sic]. Hello Tylenol, my new best friend! ... With over a year clean and drug free, I now know I can do this and anything I want without those devil pills. Y'know what? I fear drugs and addiction more than I fear cancer. So, I think I'll be OK."

Lung Cancer Statistics

There are two general types of lung cancer -- small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC is comprised of several subtypes: squamous cell carcinoma, large cell carcinoma, and adenocarcinoma.

According to the, there will be 235,760 new cases of lung cancer in 2021, with 131,880 estimated deaths (21.7% of all cancer deaths).

Lung cancer is the in both men and women in the U.S. In 1987, lung cancer surpassed breast cancer as the number-one cancer killer of women. Although lung cancer mortality is higher in men than women, the difference has declined in recent years, with increases in mortality in women and decreases in mortality in men.

There is a consistent difference between the types of lung cancer detected in men versus women. Men are more commonly diagnosed with squamous cell carcinoma, while, proportionally, more women are diagnosed with adenocarcinoma.

Lung Cancer in 'Never-Smokers'

While exposure to tobacco smoking is the leading cause of lung cancer, a significant number of patients have never smoked.

The term "never-smoker" is defined by the CDC as someone who has smoked <100 cigarettes in a lifetime. It is difficult to determine the exact number of never-smokers who have developed lung cancer because most population-based cancer registries (including the SEER database) do not collect information on whether patients smoke.

Worldwide, nearly half of women with lung cancer are never-smokers, compared with 15% to 20% of men. In Asia, there is an even more profound difference, with 60% to 80% of women with lung cancer being never-smokers. In the U.S., about 20% of lung cancers in women and 9% in men are diagnosed in never-smokers.

A 2017 study of over 12,000 in three representative U.S. hospitals found that the proportion of never-smokers increased from 8% in 1990 to 1995, to 14.9% in 2011 to 2013.

What causes lung cancer in never-smokers?

There are several risk factors for lung cancer in never-smokers. The most important risk factor is exposure to secondhand smoke, which accounts for 15% to 35% of lung cancer cases in non-smokers. The risk is highest for those whose smoke exposure occurred when they were younger than 25 years old. In addition, non-smoking spouses of smokers have a higher risk of lung cancer compared with those who have a spouse who also doesn't smoke.

Environmental exposures may also put a never-smoker at increased risk. Exposure to radon -- a gas present in soil, rock, and groundwater that can accumulate in homes -- over a long period of time is a risk factor, as is exposure to asbestos, chromium, and arsenic. Pollution, both indoors (from cooking oil and burning coal) and outdoors (from diesel exhaust and traffic-related factors), also poses a risk.

Several studies have shown that never-smokers who have a family history of lung cancer may be at higher risk due to genetic mutations that make them more susceptible to the disease.

Endocrine factors may also play a role in the development of lung cancer in women. A number of large randomized studies have suggested that estrogen plus progestin hormone replacement therapy may be associated with an increased risk of lung cancer. This risk appears to increase in proportion to the length of time hormone replacement therapy is used.

Other risk factors include prior use of ionizing radiation and a previous history of lung disease, such as pulmonary fibrosis, tuberculosis, and asthma.

Disease Differences Between Never-Smokers and Smokers

Never-smokers are much more likely to develop adenocarcinoma, while heavy smokers have a higher incidence of squamous cell carcinoma.

Mutations in the EGFR gene are much more common in never-smokers compared with smokers. (EGFR mutations are also more prevalent in women.) The ALK mutation is also more common in never-smokers. Recently, two other mutations, MET and ROS1, have been found to be more prevalent in never-smokers.

The precision diagnosis of these gene mutations in individual cancers has critical importance for personalized treatments. Advances in immunotherapy and targeted therapies such as ALK inhibitors, EGFR inhibitors, and ROS1 inhibitors are showing promise in prolonging life in lung cancer patients.

Michele R. Berman, MD, is a pediatrician-turned-medical journalist. She trained at Johns Hopkins, Washington University in St. Louis, and St. Louis Children's Hospital. Her mission is both journalistic and educational: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.