BRAF and Lung Cancer

Support for this educational program provided by Amgen, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Genentech, Lilly Oncology, Merck, Novartis and Pfizer.

When tumor tissue is looked at under a microscope, physicians can see what type of cancer it is. But physicians can also look for changes in the DNA of the tumor that might be causing the tumor to grow. Sometimes these changes are called biomarkers or molecular markers.

One way to think about it is that our DNA is like an instruction manual. If there is a typo in the instruction manual, the cell receives wrong instructions and can grow into cancer. Biomarker testing looks for those typos, so physicians know if you are a candidate to receive a targeted therapy that directly addresses those typos. 

An error in the BRAF (pronounced B-raf) gene is one biomarker that physicians look for in non-small cell lung cancer. If you have non-small cell lung cancer, it is important to talk to your doctor about comprehensive biomarker testing to see if you have an error in the BRAF gene or another biomarker. The results of this testing influence your treatment options. To learn more about biomarker testing, visit Lung.org/biomarker-testing. 

What is the BRAF-positive lung cancer?

BRAF is the name of both a gene and a protein. The BRAF protein helps control cell growth. When there is a mutation in the BRAF gene, it creates an abnormal protein that sends signals that lead to uncontrolled cell growth and cancer.  The BRAF protein works with another protein called MEK to regulate the growth of cells.

There are different mutations within BRAF, but the one with FDA-approved treatment in lung cancer is BRAF V600E. This mutation is a specific variation in the BRAF protein. In cells with this mutation, BRAF can always turn on the MEK protein.  This is why you might hear doctors talk about the protein MEK when trying to target BRAF mutations.

How do you know if you have a BRAF-positive lung cancer?

BRAF mutations can be found in several ways. The pathologist can use a test to look specifically for BRAF mutations in the tumor. However, most physicians prefer a testing approach that can look for mutations in multiple genes at one time using a single biopsy. This is called comprehensive next-generation sequencing (NGS). This type of testing places tissue from a patient’s tumor (gathered from a biopsy) in a machine that looks for a large number of possible biomarkers at one time. There may be some situations where a patient can’t undergo the biopsy needed to perform NGS, and so liquid biopsy is recommended. A liquid biopsy can look for certain biomarkers in a patient’s blood. Talk to your doctor to make sure one of these tests was performed.  

Learn more about the different types of biomarker tests here.

Who is most likely to have BRAF-positive lung cancer?

BRAF mutations have been reported in about 4% of non-small cell lung cancers (NSCLC). They are most common in adenocarcinoma non-small cell lung cancer. BRAF V600E mutations specifically occur in about 1-2% of non-small cell lung cancer patients. Most patients with BRAF V600E tend to have a smoking history. 

What is the course of treatment like for someone with a BRAF-positive lung cancer?

First-line treatment for BRAF V600E mutations in lung cancer is either:

• a combination of the targeted therapies dabrafenib and trametinib (pills that target the mutation) or 
• immunotherapy with or without chemotherapy

The targeted therapy drug combination helps address the BRAF mutation (dabrafenib) and the MEK protein (trametinib). Patients with a different type of BRAF mutation should ask their doctor about a clinical trial. The standard of care for patients with a different BRAF mutation is immunotherapy with or without chemotherapy.

Work with your doctor to discuss your goals and options each time you have to make a treatment decision. The three big questions to ask are:

1. What is the goal of this treatment?
2. What are the potential side effects?
3. What other options do I have?

Research is happening at a rapid pace and your doctor should be up to date on the recommendations for your specific type of lung cancer. If you don’t feel comfortable with the answers you are receiving, do not hesitate to seek out a second opinion.