What Is EGFR-Positive Lung Cancer?

Management of EGFR-Positive Lung Cancer

In This Article

EGFR-positive lung cancer refers to lung cancers that show evidence of an EGFR mutation. EGFR, or epidermal growth factor receptor, is a protein present on the surface of both healthy cells and cancer cells. When damaged, as can occur in some lung cancer cells, EGFR doesn't perform the way it should. Instead, it causes rapid cell growth, helping the cancer spread.

Gene testing can identify an EGFR mutation, and advances in lung cancer treatment have made it possible to target these proteins to halt the growth of cancer cells. These drug treatments won't cure your lung cancer, but they can help you manage the disease and stave off serious symptoms.

Risk Factors and Prevalence

The nucleus of every cell contains your unique DNA, which is comprised of genes. These genes act as instruction manuals for your body. EGFR plays an important role in controlling cell division and survival—for better or, in the case of mutations, for worse.

According to research, different ethnicities are more susceptible to EGFR mutations. People of Asian descent who develop non-small cell lung cancer (NSCLC) are almost 47% likely to have the mutation. Among those of Middle-Eastern or African descent, the estimate is approximately 21%. While those of European heritage have a 12% chance.

There are several common factors related to the EGFR mutations. Those more likely to have the mutation are patients diagnosed with non-small cell lung cancer who are:

While the EGFR gene is most often associated with adenocarcinomas, some types of squamous cell carcinoma are affected by the protein as well. In these cancers, growth isn't related to a mutation but to EGFR amplification, which causes rapid growth and results in highly aggressive tumors.

Symptoms of EGFR-Positive Lung Cancer

Symptoms relate to the type of cancer one has rather than the fact that it is EGFR-positive. Because EGFR mutations are most often associated with lung adenocarcinomas, symptoms may not appear during the early stages of the disease.

Adenocarcinomas tumors appear on the outer areas of the lungs. Since they are not near the airways, breathing may not be affected until the cancer has progressed to an advanced stage. Typical early symptoms of lung cancer such as fatigue, mild shortness of breath, or upper back and chest pain may not be present or might mistakenly be attributed to other causes.

When symptoms do finally appear, they are similar to the signs associated with other types of lung cancer, including:

Diagnosis

All patients diagnosed with non-small cell lung cancer, especially those specifically diagnosed with adenocarcinoma, are evaluated for EGFR genetic mutations.

The presence of an EGFR mutation is determined by molecular profiling (gene testing). The process requires your doctor to conduct a lung biopsy to get a tissue sample that is then tested in a lab. The DNA of the tumor cells is analyzed to determine if it contains any mutations in the EGFR gene.

Doctors may also be able to check for the mutations via a special blood test called a liquid biopsy, which analyzes DNA that has been shed from tumor cells in your blood. Often, the DNA sample from a blood draw is not significant enough to make a clear diagnosis, but research is being done to find effective ways to use liquid biopsies in the diagnosis or monitoring of lung cancer.

The EGFR gene is divided into 28 numbered sections called exons, each of which are at risk for mutation. The most common EGFR mutations include missing genetic material on exon 19 (19-del) or damage to exon 21 (21-L858R). These two mutations account for about 85% of the EGFR mutations of lung cancer cells.

It's estimated that EGFR and other driver mutations (i.e., DNA changes that determine the development of the cancer) are present in as many as 70% of people with lung adenocarcinoma. As such, when you undergo genetic testing, your doctor will check for other driver mutations that can be targeted by treatments, including:

Treatment

Lung cancer with EGFR mutations is often not diagnosed until the disease is at stage 3 or 4, so treatment doesn't usually focus on curing the cancer; instead, it's aimed at managing the spread and relieving symptoms.

Historically, chemotherapy had been the first course of treatment for almost all cases of advanced non-small cell lung cancer, but FDA-approved targeted therapy drugs are now the main choice for treating tumors with EGFR mutations.

These medications tend to have fewer side effects than chemo and will not kill healthy cells. The introduction of targeted therapy medications over the past decade has given patients new opportunities to stop lung cancer from advancing while improving survival rates and quality of life.

The targeted therapy drugs Tagrisso (osimertinib), Tarceva (erlotinib), and Iressa (gefitinib) are known as tyrosine kinase inhibitors because they prevent the EGFR protein on mutated cells from triggering tyrosine kinase, an enzyme within cells that activates cell division and, thus, multiplies cancer cells. 

Tagrisso is now recommended as a first line treatment for EGFR mutations because it's best able to penetrate into the cerebrospinal fluid and pass through the blood-brain barrier to help fight lung cancer with brain metastases—particularly important because lung cancer often spreads to the brain.

To treat EGFR-positive squamous cell lung cancer, doctors use a monoclonal antibody (man-made antibody) such as Portrazza (necitumumab) that blocks the activity of EGFR.

Clinical Trials

Tremendous progress has been made in both the identification of genetic changes with lung cancer and targeted therapies to treat these changes. There are many clinical trials looking at other medications to treat EGFR mutation-positive lung cancer, as well as treatments for other molecular changes in cancer cells.

Side Effects

The most common side effect of tyrosine kinase inhibitors is a skin rash. Less frequently, diarrhea may also occur.

Tarceva (erlotinib) skin rashes (and rashes from other tyrosine kinase inhibitors) resemble acne, occurring on the face, upper chest, and back. If no whiteheads are present, a topical corticosteroid cream—a hydrocortisone cream, for example—is used. If whiteheads are present and the rash looks infected, oral antibiotics are prescribed. In some cases, the tyrosine kinase inhibitor dose may be reduced.

Resistance to Treatment

Unfortunately, though lung cancers may respond very well to targeted therapy medications at first, they almost always become resistant over time. When this happens, doctors look to other targeted therapy drugs or new approaches to treatment, which may include combining treatments.

The length of time it takes for targeted therapy resistance to develop varies, but nine to 13 months is common; although, for some people, medications can continue to be effective for many years.

If there are signs that the cancer is starting to grow again or spread, your doctor will order a repeat biopsy and additional genetic testing to determine if there are further mutations or drug resistance.

Support and Coping

If you’ve recently been diagnosed with lung cancer, you're doing one of the best things you can do right now—taking the time to learn about your cancer.

In addition to growing your understanding about your disease, learn how to advocate for yourself as a cancer patient.

The lung cancer support community is strong and getting stronger. Many people find it helpful to become involved in these support groups and communities not only as a way to find help from someone who has "been there" but as a method of staying abreast of the latest research on the disease.

A Word From Verywell

The treatments—and thankfully survival rates—for lung cancer with EGFR mutations are improving, and there is a lot of hope. Still, cancer is a marathon, not a sprint. Reach out to loved ones and allow them to help you. Keeping a positive attitude with cancer is helpful, but making sure you have a few close friends you can be completely open with (and express your not-so-positive feelings to) is as well.

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