How They Affect Lung Cancer

When you hear the word “genes” you might think of the ones you inherit from your parents. But while genes and lung cancer are related, very few known genes can transfer a higher risk of lung cancer from parent to child.

“We do not see those [people] very often at all, because most [people] with lung cancer have no inherited cause, ”says Kerry Kingham, senior cancer genetics advisor at Stanford Health Care.

There are a few exceptions, she said. When several members of a family have lung cancer with no obvious external cause (such as smoking), you may want to see a genetic counselor.

“But even in these [people], we do not often find the cause.

Only about 1% of these cases have inherited mutations.

“And when we find the inherited mutations and are able to test other family members, there really aren’t any good guidelines that tell us exactly what to do for them outside of more careful screening. Said Kingham.

What’s much more important, she says, is testing for cancer cells after diagnosis.

The most common tie

Tiny pieces of genetic material (which your doctor may call “proteins”) inside previously healthy lung tissue cells can change or “mutate” to form cancer cells. As cells divide, they continue to pass these changes, or “mutations,” to new cells, which form tumors.

Doctors don’t know what causes these mutations. But you don’t inherit them from your parents and you can’t pass them on to your children. It’s also not your fault that you get them. These mutations “just happen,” Kingham says. They are not due to something you did or did not do.

“It’s no one’s fault. It’s not what you ate. It’s not because you looked at the moon the wrong way or lived an unhealthy lifestyle, for most people, ”she says.

“It’s just sometimes cells make mistakes when they divide.”

When genetic testing matters most

Certain genetic mutations in lung cancer can help doctors make a treatment plan. Doctors call these mutations “biomarkers”.

Some lung cancer biomarkers are important to understand and treat differently, says Heather Wakelee, MD, thoracic oncologist, professor and head of the Division of Medical Oncology at Stanford University Medical Center.

EGFR (epidermal growth factor receptor) is probably the most common. About 10% to 15% of non-small cell lung cancers are EGFR-positive, which means they have a cancerous mutation in the EGFR gene.

This is what doctors call a “motor mutation,” which means that is the reason there is cancer. This mutation often affects some people with lung cancer, such as:

  • Non smokers
  • Women
  • People of Asian or East Asian descent
  • Those who have pulmonary adenocarcinoma (a type of lung cancer)
  • Young adults with lung cancer (Half of these cases are EGFR positive.)

But everyone with a diagnosis of non-small cell lung cancer (NSCLC) should have an EGFR test, not just those in these high-risk groups, Wakelee says.

“It is really essential that every non-small cell lung cancer tumor is tested for EGFR, regardless of its stage,” she says.

And not just for EGFR. Your doctor should test at least seven other genetic biomarkers if they diagnose you with lung cancer.

They include:

  • ALK
  • ROS1
  • RET
  • MEET
  • BRAF
  • NTRK
  • HER2

Each represents up to 5% of NSCLC cases.

The reason these tests are so important for people with NSCLC is that scientists have designed targeted cancer therapies for tumors with these particular genetic mutations.

“If we find a tumor mutation, we can treat it with a better drug – often a drug that is better tolerated in addition to being more effective,” says Wakelee. “This is true now for eight different genes, so it is very important that tumors are tested before treatment begins, if possible.”

Simply put, these drugs target a protein stuck in the “on” position and deactivate it.

You can take most targeted drugs in pill form at home instead of intravenous chemotherapy in the hospital. And they’re not only more effective, they’re generally much easier on your system than other cancer treatments, Wakelee says.

When there is a viable gene to target, these therapies shrink tumors more than chemotherapy or immunotherapy, and treatment often works longer.

For people with early-stage NSCLC who have had surgery, an EGFR drug called osimertinib (Tagrisso) can delay the cancer coming back and reduce the likelihood of the cancer spreading to the brain.

People with EGFR positive stage IV NSCLC can also get Tagrisso because it is much more likely to shrink the tumor and work longer than any other type of treatment.

Small cell lung cancer does not yet have approved targeted therapies, although clinical trials continue to explore the possibility.

The importance of patience

In addition to your genetic test panel (sometimes called “molecular tests”), your doctor should look for another biomarker called PD-L1. Levels of this protein indicate whether you are more likely to respond to treatment with immunotherapy drugs.

This can complicate matters, Wakelee says, because results from PD-L1 usually arrive long before the mutation occurs.

A high PD-L1 often means that immunotherapy may be successful.

“And so it’s tempting to just act on that,” Wakelee says. But this is not always the best route. If you have certain mutations, like EGFR, immunotherapy may do more harm than good. And it could make future targeted therapies more toxic to your system.

That’s why, says Wakelee, it’s important to wait to come back all results before making a decision.

And this is just one example of the possible complications. In some cases, there are so many complex tumor factors that your healthcare team will come together with a group called the Tumor Molecular Board made up of a combination of:

  • Expert doctors
  • Medical oncologists
  • Surgeons
  • Radiotherapists
  • Researchers
  • Geneticists
  • Pathologists

“For someone who has just been diagnosed with stage IV lung cancer, the wait can be extremely stressful,” says Wakelee. “Most people want to start treatment immediately. But it is really important to wait until you have the full history of the tumor to understand the best option. “

They’re not just smokers

There can be a hideous stigma that if you have lung cancer you must have caused it by smoking. That’s unfortunate, says Yasir Y. Elamin, MD, a thoracic medical oncologist and assistant professor of thoracic medical oncology at the University of Texas MD Anderson Cancer Center.

He says that is also wrong.

Although smoking remains the main risk factor for the disease (aside from age), up to 1 in 5 people who die from lung cancer each year have never smoked. This puts lung cancer at the top of the list of the deadliest cancers in the United States in people who have never smoked.

“I don’t think anyone deserves to have lung cancer, whether they are a smoker or a non-smoker. But I think we need to understand more and more that lung cancer is not a disease exclusively related to smoking, ”says Elamin.

This is especially true of lung cancers that respond to targeted therapy.

“For the most part, they are not related to smoking.” Said Elamin. “I think it’s a very painful reminder that lung cancer is not just linked to smoking. So I hope this helps us to remove some of the stigma around this.

The future of targeted therapies

Targeted therapies can improve quality of life with fewer side effects and better results. But there are frustrations with these treatments. One of them is that people tend to oppose them.

“This is one of the sad realities of targeted therapy,” Elamin says.

It may take 2 or 3 years, but eventually virtually everyone who takes targeted therapy develops resistance, especially those who start treatment in the later stages of the disease. A lot of new research is focused on how to overcome this problem.

“We are focusing on how and why resistance is developing,” Elamin says.

The hope is to find ways to delay or overcome resistance, or better yet, prevent it.

Overall though, Elamin is very optimistic. It reports a recent study of the drug alectinib (Alecensa), a therapy targeted for the biomarker ALK. Research has found that over 60% of people with advanced NSCLC who have taken treatment have lived at least 5 years longer.

“Imagine the difference,” he says. “When I was doing my training, the 5-year survival for the same group was 5-6%. It’s incredible.”

Of course, 60% is not the goal, but Elamin remains encouraged.

“We hope to have it 90% or 100% someday. But I think we’ve made some progress and in this case the numbers speak for themselves.”

Sources

SOURCES:

Heather Wakelee, MD, thoracic oncologist, professor of medicine, Stanford University Medical Center.

Yasir Y. Elamin, MD, thoracic medical oncologist, assistant professor of thoracic medical oncology, MD Anderson Cancer Center.

Kerry Kingham, Senior Cancer Genetics Advisor, Stanford Health Care.

American Cancer Society: “Lung Cancer Risks for Non-smokers”, “Lung Cancer Screening Tests”.

CDC: “Lung cancer in people who have never smoked.”

Lung Cancer Foundation of America: “What is EGFR-positive lung cancer and how is it treated?”

Memorial Sloan Kettering Cancer Center: “Lung Cancer Genomic Test (EGFR, KRAS, ALK).”

UC San Diego Health: “Molecular Tumor Board, Center for Personalized Cancer Therapy.”


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