All About Cancer

Why Are Women Who Never Smoked Getting Lung Cancer?

Lindi Campbell remembers the date: Dec. 6, 2017. That was when she found out she had lung cancer. "I was so shocked," she says. She had never smoked, and she didn't know anyone with lung cancer, let alone any other "never-smokers" like her. That made her feel isolated.

So besides taking care of her own health, she set out to connect with other people who could relate. A year after her diagnosis, she founded Breath of Hope Kentucky, a nonprofit lung cancer advocacy and outreach group.

Campbell has connected with more than 20 never-smokers in or from her state. She noticed something unusual: Only one of those people is male.

It's a small example of a pattern that's stumped scientists: Why are women much more likely than men to get lung cancer if they never smoked?

Cigarette smoking is, by far, the top cause of lung cancer. But about 15% to 20% of cases in the U.S. Happen in never-smokers -- people who've never lit up or smoked fewer than 100 cigarettes in their life.

In the U.S., women make up about two-thirds of lung cancer cases in never-smokers, says Alice Berger, PhD, a laboratory researcher at the Fred Hutchinson Cancer Research Center in Seattle.

That's unusual. Cancer is generally more common among men.

"In the last 5 years, there's been a lot of attention on, Why is this happening? And why are women disproportionately affected?" Berger says.

You might remember when Dana Reeve, the wife of the late actor Christopher Reeve, died of lung cancer at age 44. Reeve had never smoked. Her cancer was already at stage IV when it showed up after she got an X-ray because she had a cough that wouldn't go away. That was back in 2006 -- and cases like hers are still hard to explain.

The reasons why aren't clear. It could be differences in the immune system between women and men, Berger says. She and other scientists are looking into other factors: gene variants, hormones, and things in the environment like air pollution or radon.

"But that research is still in the early stages," Berger says. A mix of factors may be involved.

Although Campbell wasn't a smoker, she had been exposed to secondhand smoke. "I grew up in a home of smokers. There were nine people, and only two of us had never smoked. I was the youngest and the only one who got lung cancer."

Lung cancer tumors in people who have never smoked are often different from those that occur in poeple who have smoked. "There are distinct differences in the immune landscape," says Ramaswamy Govindan, MD, a professor of medicine at Washington University in St. Louis.

Most never-smokers with lung cancer -- as many as 78% to 92% of them -- have a "targetable" gene change, or biomarker, that may respond to an FDA-approved drug, according to research by Govindan and his colleagues. The epidermal growth factor receptor (EGFR) mutation is a common one, especially in female never-smokers.

Never-smokers with lung cancer need to get high-quality biomarker testing, Govindan stresses. These tests are needed to see what immunotherapy medications could target the tumors -- and potentially save lives. And these simple genetic tests don't always check for all the options.

Govindan has this message for doctors: "You have to look diligently for a potential targetable mutation by doing appropriate testing," he says. "Sometimes we don't get enough material and we only look for a few genes. If they're not there [with the first sample], don't stop there."

These biomarkers are inside the cancer's DNA. They're not something you're born with. Govindan says only about 5% to 6% of never-smokers tend to inherit a gene that makes them more likely to get lung cancer.

Cancer deaths had their steepest drop in the U.S. From 2016 to 2018. That was largely due to a drop in lung cancer deaths, thanks to targeted therapies and immunotherapy, says Joy Feliciano, MD, an associate professor of oncology at Johns Hopkins University School of Medicine.

Targeted therapies are different from chemotherapy. They go after certain parts of your tumor's DNA, like those biomarkers. These drugs don't help everyone and aren't a cure. But they work by blocking instructions that tell your cancer cells to keep growing.

"If you're a nonsmoker and you have a targetable mutation, you can get an oral drug," says Roy Herbst, MD, PhD, chief of medical oncology at Yale Cancer Center/Smilow Cancer Hospital. "About 70% to 80% of the time, the tumor will shrink."

Campbell had surgery to remove the original tumor from her right lung. But a few nodules showed up in her lung's left lobe a year after her surgery. In 2020, she had the tissue removed. It was cancer. This time her doctor did genetic testing, which showed that Campbell had a gene mutation called the EGFR-exon-19 deletion. She's been taking a targeted medication called osimertinib (Tagrisso) ever since. Her lung cancer hasn't spread outside of her lungs.

Immunotherapies are drugs that work on your immune system to help it fight off cancer cells. There are different types. These include "checkpoint inhibitors" to block a protein common in smoking-related tumors.

But "these tend to not work as well in nonsmokers because there's not as much inflammation to target," Berger says. And like targeted therapies, they don't work for everyone. But in the right people, they can make a big difference.

Anyone who has lungs can get lung cancer. But it's much more likely for some people than others -- especially those who smoke.

Yearly screenings are only recommended for certain high-risk groups. That's usually heavy smokers who are 50 to 80 years old.

There are no clear guidelines on how to screen for lung cancer early in never-smokers, even if you have a family history of the disease. Experts agree that's a big problem. But it's not one they know how to solve, yet.

We need some sort of early detection methods.

Lindi Campbell.

Screening involves getting a scan. But if the scan shows something abnormal, you usually have to get an "invasive" procedure, such as a biopsy, to find out if it's cancer, Feliciano explains. "So any screening test that becomes widely used has to be something where the benefits outweigh the risks," she says.

Those risks include repeated exposure to low-dose radiation (if you get several scans over the years) and lung surgeries to find out that you don't have cancer. "It's not like a breast biopsy where you can do it really simply, right at the time of the mammogram," Herbst says.

"We need some sort of early detection methods," Campbell says. "If we represent 20% of 230,000 people a year in the U.S. Getting diagnosed, that's close to 45,000 people. That's a big number."

Many never-smokers with lung cancer are diagnosed by chance. A doctor may order a chest X-ray for another health problem and find something unusual in the lungs. That's what set Campbell on the path to her diagnosis.

She had a little chest pain she blamed on acid reflux, a passing symptom she thinks was unrelated to her cancer. "But thankfully, my doctor said, 'Let's just do a chest X-ray to be sure everything else looks good.' "

A follow-up CT scan showed a 1.2-centimeter nodule in Campbell's right lung. She says that didn't "set off alarm bells" for her first pulmonologist. It took another 2.4 years and at least six doctors and nine scans to find out she had lung cancer.

"Everything it took to get that early diagnosis for someone who'd never smoked, it's a miracle I even got to that point, and they did catch it early," Campbell says.

You may not have any symptoms early on, or they may be vague. Campbell had only a very mild cough by the time they found her tumor. And it's something she would've blamed on allergies had her primary doctor not ordered those first scans.

But lung cancer symptoms in females who never smoked are the same as for anyone else. Here are some things Campbell says she and other women in her lung cancer community had before their diagnosis:

An ongoing dry cough

Coughing up blood

Hoarseness or total loss of voice

Shortness of breath

Lung or throat "infections" that didn't respond to antibiotics

Some other signs included:

Experts agree you should look into any health problem that doesn't go away. Tell your doctor if you have a family history of cancer, and push for more tests until you get the reason behind your symptoms.

"I would be persistent," Herbst says. If a scan shows an abnormal growth, "you need a biopsy to figure out what's going on."

In 5 to 10 years, Herbst predicts we'll know a lot more about what raises the odds for lung cancer in people who don't smoke. He says screening and detection methods, including cancer-sensitive blood tests, are sure to get better, too.

"I think someday soon, we'll be able to tell just from the X-ray whether it's benign or malignant," he says.

Campbell hopes for a cure. But for now, she swallows a pill every night and gets scans and bloodwork every 3 months. She's had one recurrence of her lung cancer, a year after her first operation. Once a year, an MRI takes pictures of her brain to check for tumors. She's thankful her treatment helps her live longer. But she wants more funding and research devoted to lung cancer among nonsmokers.

Campbell's home state ranks highest in the U.S. For lung cancer deaths. And unlike her, few get an early diagnosis. The native Kentuckian hopes her nonprofit advocacy group can help erase the stigma that comes with the disease and raise awareness about nonsmoking survivors like her.

"It's like the Dr. Seuss book with the dust speck: We're here! We're here!" she says.

What Does Lung Cancer Look Like?

If you have lung cancer, imaging tests like a chest X-ray will typically show a visible mass or nodule in your lungs. It will look like a white spot against the backdrop of a black lung.

An estimated 238,340 in the United States will be diagnosed with lung cancer by the end of 2023. Lung cancer is the second most common form of cancer in men and women in the United States.

Though a lung cancer diagnosis is serious, new and increasingly effective treatments are being researched every day. Early diagnosis and treatment may lead to a positive outlook.

Though lung cancer is common and can feel scary, the number of new lung cancer cases is decreasing, most likely due to positive lifestyle changes in the population and new treatments.

Here are some pictures to illustrate what lung cancer looks like.

Non-small cell lung cancer (NSCLC)

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, making up about 80-85% of all cases. There are three main subtypes of NSCLC: Adenocarcinoma, large-cell carcinoma, and squamous-cell carcinoma.

Adenocarcinoma: This is cancer that begins in the cells that secrete substances like mucus.

Large cell carcinoma: This type can appear in any part of the lung and spread faster than other types.

Squamous cell carcinoma: This cancer starts in cells that line the airways called squamous cells. The cancer cells tend to be found near major airways.

There are also two less common types of NSCLC:

adenosquamous carcinoma

sarcomatoid carcinoma

Small cell lung cancer (SCLC)

Only about 10-15% of all lung cancers are SCLC. This type can spread quickly and is often more challenging to diagnose early.

SCLC often responds well to chemotherapy and radiation, though it may often recur after treatment.

Lung cancer tumors

Other types of tumors can also occur in the lungs. Called carcinoids, these tumors grow slower than other types of lung cancer.

Carcinoids typically form in the lungs' airways — the bronchi (large airways) or bronchioles (narrow airways). A person may have different symptoms depending on where the tumor is growing, and the treatment may be different depending on where, exactly, the tumor is.

Carcinoids don't usually spread to other areas of the body. They aren't caused by smoking.

Several tests will allow your doctor to make a lung cancer diagnosis:

Chest X-ray

If you have any symptoms of lung cancer, your doctor may order a chest X-ray. A chest X-ray of someone with lung cancer may show a visible mass or nodule.

This mass will look like a white spot on your lungs, while the lung itself will appear black. However, an X-ray may not be able to detect small or early-stage cancers.

CT scan

A computed tomography (CT) scan is often ordered if there is something abnormal on the chest X-ray. A CT scan takes a cross-sectional and a more detailed image of the lung. It can give more information about abnormalities, nodules, or lesions — small, abnormal lung areas seen on X-ray.

A CT scan can detect smaller lesions not visible on a chest X-ray. Cancerous lesions can sometimes be distinguished from benign lesions on chest CT scans.

Your doctor cannot diagnose cancer with only an image from a CT scan or an X-ray. If they are concerned about the results of image tests, they will order a tissue biopsy.

Sputum cytology

If you can produce phlegm when you cough, microscopic cancer cells may be seen in this form of screening.

Biopsy

In a biopsy, your physician will take a tissue sample from your lungs for examination.

This sample may be removed via a tube placed down your throat (bronchoscopy), an incision at the base of the neck (mediastinoscopy), or by making an incision in the chest wall and using a needle to collect the sample.

A pathologist can then analyze this sample to determine if you have cancer. More testing may be needed to determine if the cancer has spread to other areas.

What is stage 1 lung cancer like?

This depends, first of all, on the type of lung cancer you have. In the case of NSCLC, stage 1 is when the cancer has not yet spread past the tumor itself to the lymph nodes or anywhere else.

What are the three warning signs of lung cancer?

Usually, you wouldn't develop symptoms of lung cancer until your disease is advanced. If you're experiencing a cough, shortness of breath, hoarseness, or any other signs that might be associated with lung cancer, and these symptoms do not improve with treatments for things like a viral illness or pneumonia, ask your doctor for a screening.

Can you see lung cancer on the skin?

In rare cases, lung cancer can affect your skin. If you notice any yellowing of your skin (jaundice) or unusual skin lesions, speak with your doctor as soon as possible.

Lung cancer is one of the most common types of cancer and may require quick and aggressive treatment. Some major milestones have been reached in clinical research to find more effective methods of treating it.

If you're worried about the risk of lung cancer, speak with your doctor about screening and prevention. They can help you determine what steps to take to treat or prevent lung cancer and any related conditions.

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