BRAF

What is the BRAF biomarker?

The BRAF gene is present in all of the cells in our body and it holds the instructions for making
a protein by the same name, BRAF. The normal (wild type) BRAF protein works together with a
group of proteins called the EGFR/RAS/MAPK pathway to stimulate growth and division of cells
in response to bodily needs and environmental cues. When the BRAF gene is mutated, it instructs
an abnormal BRAF protein to continuously signal for cells to grow, and it cannot be turned off.1,2

A BRAF gene mutation is A BRAF mutation is NOT hereditary

The mutation happens
found in about
early, when the cancer
starts to develop, driving
uncontrolled growth.
10-15%
This is called a
driver mutation.
of colorectal cancer
patients.1
(not a germline mutation) and will NOT
pass from one generation to another.
In all cases, a BRAF mutation happens
randomly and it is a somatic or
acquired mutation. The majority of
patients with a BRAF mutation carry the
mutation called V600E, although other,
less frequent BRAF mutations also exist.1,2

When and how should I have BRAF biomarker testing?

The National Comprehensive Cancer Network (NCCN) and American Society of Clinical
Oncology (ASCO) recommend BRAF testing for everyone diagnosed with stage IV, metastatic
colorectal cancer (mCRC) and before initiating therapy with anti-EGFR inhibitors.3,4

Your doctor may also recommend re-testing the tumor for new or additional mutations when
chemotherapy treatment stops working and the tumor grows again.3,4

What do I do with this information?

Knowing the details of tumor biomarkers can help you and your doctor make decisions about
personalized treatment with therapies tailored specifically to the characteristics of your tumor.

 The BRAF V600E mutation is a prognostic biomarker of aggressive tumor growth. The
mortality risk for patients with a BRAF mutation is more than two times higher than for those
with a normal BRAF gene. Therefore, knowing about a BRAF gene mutation indicates the need
for aggressive treatment.1,2
 The BRAF mutation is also a predictive biomarker, which means it predicts that your tumor
is unlikely to respond to treatment with EGFR inhibitors when given alone or in combination
with chemotherapy.3,4

continued 4
What treatment options are available?

BRAF inhibitors are drugs that

• In colorectal cancer, BRAF inhibitors can significantly
can turn off and stop mutated lower the risk of death for patients with the BRAF
BRAF protein activity. V600E mutation when given together with one or
two additional inhibitors.6

• Patients can only receive these drug combinations

as a second or third line of therapy after their tumor
did not respond to chemotherapy.3,4,6

• There are several ongoing clinical trials that are

looking at whether mCRC patients with a BRAF
Unfortunately, in colorectal
mutation can avoid chemotherapy and instead
cancer, these drugs are not receive the combination of BRAF, MEK, and EGFR
effective by themselves inhibitors as a first-line therapy.
(like in Melanoma).5

What are the potential side effects of BRAF inhibitors?

Every treatment has the potential to cause some side effects. Some people may be more sensitive
than others to a drug. It also depends on your other treatments, medications, vitamins, and herbal
supplements. Tell your doctor or pharmacist about all the medications, vitamins, and treatments
you take.

Some of the most common side effects associated with BRAF inhibitors are headache and
dizziness, fatigue, diarrhea or constipation, nausea and vomiting, skin problems, joint or muscle
pain, and anemia/low red blood cell levels. It is unlikely that you will experience all these side
effects, but you might have some of them. Call your doctor immediately if you are experiencing
severe symptoms.

For more on side effects of other chemotherapy regimens: ccalliance.org/colorectal-cancer-

information/treatments/side-effects

For additional questions and assistance: ccalliance.org/patient-family-support/helpline

For our Clinical Trial Finder: ccalliance.org/ctf

1
Vacante M. et al., Biomarkers in colorectal cancer: current clinical utility and future perspectives. 2018 World J. Clinical Cases 6: 869-881
2
Dekker E et al., Colorectal cancer 2019 Lancet 394:1467-1480
3
NCCN clinical cancer practice guideline in oncology (NCCN Guidelines) Ver.4-June 15, 2020 http://nccn.org/professionals/physician_gls/pdf/colon.pdf
4
NCCN clinical cancer practice guidelines in oncology (NCCN Guidelines) Ver.6-June 25, 2020 https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf
5
Sepuldeva AR et al, Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline from the American Society for Clinical Pathology, College of American
Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. 2017 J. Clinical Oncology 35:1453-1486
6
Kopetz S. et al Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. 2019 New England Journal of Medicine 381:1632-1643

ccalliance.org | Helpline: (877) 422-2030

The Colorectal Cancer Alliance is a national organization committed to ending colorectal cancer within our
lifetime. We are your allies — a national network of passionate survivors, caregivers and advocates dedicated to
helping you and your family navigate all aspects of the disease, from diagnosis and treatment to a lifetime of
progression-free survival. We are a community of people eager to share experiences, address your concerns,
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