Trying to cope with the mountain of information that accompanies a diagnosis of cancer is a formidable challenge. Molecular profiling may not be the first topic that comes to mind in your discussions with your oncologist, but the search for biomarkers could be an important part of your treatment.
During the past decade precision medicine has become a common approach to the treatment of some forms of cancer. Molecular profiling makes precision medicine and targeted therapy possible by identifying biomarkers that reveal characteristics of a specific cancer. This information is useful to the oncologist in important ways, including providing help in selecting the treatment that is most likely to be effective, monitoring the effectiveness of treatment, determining the prognosis, and watching for recurrence. Some biomarkers indicate hereditary mutations that increase the risk of developing a particular cancer.
If the decision is made to proceed with molecular profiling, a sample of your cancer cells will be sent to a specialized laboratory. Molecules for testing can be obtained from blood, body fluids, or tissue from a tumor biopsy. The lab will perform multiple tests to examine protein changes, genetic mutations, and various substances in the sample to determine which biomarkers were present and at what levels they were found.
The results of these tests may identify biomarkers that can help predict how aggressively the cancer will grow or indicate whether your tumor would respond to a known therapy. Your oncologist will interpret the test results and will probably discuss treatment options with you based on these results.
Of course, there are limits to the effectiveness of molecular profiling, and there are several reasons biomarkers alone cannot be used to diagnose cancer. Not all patients with a particular type of cancer will have an elevated level of the corresponding biomarker. Some biomarkers are present in more than 1 type of cancer, and some can be elevated in people who do not have cancer. In addition, many cancers do not yet have an identified biomarker.
Molecular profiling is an area of medicine that continues to advance as new targeted therapies are developed, and the standard of care for cancer patients is changing based, in part, on these advances.
If no one on your oncology team has suggested testing for biomarkers, you may want to ask your oncologist: Is molecular profiling appropriate for my form of cancer?
Tests Used in Molecular Profiling
Molecular profiling uses many complex technologies to test for cancer biomarkers. As the National Comprehensive Cancer Network (NCCN) explains, these advanced biomarker tests can be categorized into 1 of 3 groups: chromosome, gene, and biochemical. You will find that various researchers and cancer organizations have given these groups different names when describing their functions. Chromosome, or cytogenetic, tests are used to detect abnormalities in chromosome structure. Gene tests, also called molecular genetic tests, may assess 1 gene or a short strand of DNA to identify mutations. Biochemical tests evaluate proteins and their functions.
Chromosome Tests
Chromosome tests look for abnormal changes that often occur within the chromosomes of cancer cells. These changes may include having parts of a chromosome expanded, switched, or eliminated. Translocation, another abnormal change, occurs when part of one chromosome attaches to another chromosome.
Tests can be performed on white blood cells, also known as T lymphocytes, and on cells from bone marrow, amniotic fluid, and other tissues. At the lab, the cells are cultured, put on microscope slides, and stained. The distinct bands of each chromosome become visible, and the structure of the chromosome can then be analyzed. For example, the Philadelphia chromosome, which is the defining characteristic of chronic myelogenous leukemia, is created by translocation and detected using bone marrow tests that measure the number of cells that have the Philadelphia chromosome.
Gene Tests
The various individual tests that are part of current gene testing technology are designed to identify changes in DNA. Molecular genetic tests, or gene tests, look for evidence that genes are missing, incorrectly placed, have extra copies, or have mutations. Targeted treatment depends on obtaining this genetic information.
Using sophisticated equipment, a DNA test can be performed on a very small sample of cells from any tissue. A single gene test can look for a specific biomarker, but gene-expression panels can look for multiple biomarkers at the same time. Finding mutations that match those known to have responded to specific therapies may lead to a treatment option appropriate for a specific cancer. Based on gene tests, targeted therapies have been used to treat certain breast, esophageal, and lung cancers. It is also true that gene testing can eliminate some targeted therapies based on the results of the tests.
Certain gene tests are used to identify inherited cancers and precancerous conditions. Examples of this type of gene test include those looking for the BRCA1 and BRCA2 genes associated with high-risk breast and ovarian cancer and a test for an altered NTRK gene that helps cancer grow.
Biochemical tests
Instead of using chromosome or gene tests to identify abnormal genes, researchers and doctors can use biochemical tests to study the proteins made by genes. If these proteins are abnormal—if there are too many of them or if they are too active—they may help the cancer to grow.
Some biochemical tests evaluate the effects of cancer by analyzing the amount of certain chemicals in the blood. For example, some cancers can cause the blood to have high levels of an enzyme called lactate dehydrogenase. If these levels drop after cancer treatment, doctors will know the treatment is working.
If your oncology team has discussed testing for biomarkers, you may want to ask: What kind of molecular profiling test might be useful in identifying biomarkers for my cancer?
Biomarkers As a Path to Precision Medicine
Since 1965, when a blood test for a tumor marker identifying colon cancer was discovered, many biomarkers have been identified and studied in an effort to improve cancer care. However, as we know, moving from laboratory research to helping actual patients is a long, hard road. There are many biomarkers known today, but there are important limits to their use in helping to diagnosis and manage cancer. The future use of biomarkers holds significant promise, and you may want to learn more about some specific biomarkers.
Breast Cancer Biomarkers
Since they were discovered in 1994 and 1995, the BRCA1 and BRCA2 genes have been studied in relation to breast cancer. These genes, which are found in all women and men, normally suppress tumor growth. However, inherited mutations in BRCA1 and BRCA2 genes have been found to increase the risk of breast cancer.
Although these genes are well-known biomarkers linked to increased risk for breast cancer, the mutations are rare. Candidates for testing include, among others, patients who have been diagnosed with bilateral breast cancer, those with a family member who has the BRCA1 and BRCA2 mutation, and those diagnosed with breast cancer at age 50 years or younger who had a close family member who had breast cancer. The American Cancer Society and the NCCN recommend an annual mammogram and MRI for women who have a high risk of breast cancer.
HER2 is a gene that can play a role in the development of breast cancer. HER2 proteins, made by this gene, normally help control the division, growth, and repair of breast cells. But if the HER2 gene mutates and malfunctions, it can make too many copies of itself, causing out of control growth. HER2-positive cancers often grow faster than cancers that are HER2 negative. There are several tests available to test for this biomarker, and there are treatments available specifically for HER2-positive breast cancer.
Estrogen receptors (ERs) and progesterone receptors (PRs) may be found in breast cancer cells. Testing for these biomarkers is done to help decide if treatment with hormone therapy is likely to be successful and to help determine the risk of recurrence. Hormone and combination therapies are available for patients who are ER/PR positive. About two-thirds of breast cancers are ER and/or PR positive.
Prostate Cancer and the PSA Biomarker
Cells in the prostate gland produce a protein known as prostate-specific antigen, or PSA. In 1994, the use of the test measuring PSA level was approved by the FDA for prostate cancer screening, and for many years the PSA biomarker has been a deciding factor in the diagnosis and treatment of most cases of prostate cancer. More recently, the reliance on PSA tests has caused controversy, and many researchers and doctors now agree that the adverse effects of unnecessary treatment are too great. Consequently, the “active surveillance” approach, which includes a recommended schedule of PSA testing, digital rectal exam, and prostate biopsy, is often recommended.
To improve PSA accuracy and reduce the number of unnecessary biopsies, the use of newer biomarkers such as PCA3 score has been suggested. Another biomarker is the PTEN gene, a tumor suppressor gene involved in regulating the cell cycle. The PTEN test may help determine the rate of progression and help the oncologist decide on appropriate therapy. There are many biomarkers in various stages of development that could change the way prostate cancer is treated, but more study is needed to determine how effective they will be.
If testing for biomarkers will be part of your diagnosis, you may want to ask: How will the results of this test affect the plan for my treatment?
