Benefits and Limitations of Tumor Markers

Biomarkers help doctors know more about an individual person’s tumor, allowing them to make better, more informed decisions about treatment options. There are two types of biomarkers: protein and molecular.

Protein biomarkers include substances that are either produced by cancer cells themselves or by other cells in response to cancer. Protein biomarkers are primarily found in the blood and, sometimes, urine. Most protein biomarkers related to cancer are used to monitor response and/or detect recurrence or progression during follow-up after treatment (Table 1).

Molecular biomarkers are changes or alterations in genes, cellular receptors, or enzymes that have been found to identify a subtype of cancer. Identifying subtypes is important for determining prognosis and also for guiding treatment. Testing for molecular biomarkers is usually done on samples of tissue taken from the tumor.

Limitations of Biomarkers

Although biomarkers are becoming increasingly valuable in treating cancer, they have limitations. For example, many protein biomarkers are not cancer specific; that is, conditions other than cancer may cause a protein biomarker to be present or be at an elevated level. In addition, the levels of some protein biomarkers are not elevated in all patients with a particular cancer. Because of these limitations, your doctor must consider other clinical information (such as results of blood tests and imaging studies) when interpreting the results of biomarker testing.

Molecular biomarkers are usually more reliable than many protein biomarkers, but these biomarkers have not yet been identified for every type of cancer. Also, testing for some molecular and genetic biomarkers is limited by the availability of laboratories that have the equipment necessary to perform the testing.

Because the treatment of your cancer often depends on the results of biomarker testing, it is imperative that the tests be carried out by approved methods at accredited facilities. You should talk to your doctor about the accuracy of your biomarker testing results and whether testing should be repeated for verification.

How Tumor Markers Are Used

Screening
Most tumor markers are not useful for screening; only 1 tumor marker (prostate-specific antigen) is used for screening
Diagnostic Aid
Tumor markers can help identify the type of cancer when considered along with other clinical factors, such as symptoms and findings on imaging studies
Determine Prognosis
Some tumor markers are factors considered when determining prognosis, or a prediction of the outcome
Guide Treatment
Some tumor markers can provide information about what types of treatment are more likely to produce a response 
Monitor Response to Treatment
Tumor markers can monitor the effectiveness of treatment, especially for advanced cancers
Detect Recurrence or Progression
One of the primary uses of tumor markers; if the level of a tumor marker is elevated before treatment, is low after treatment, and then begins to increase after treatment, it is likely that cancer is recurring or progressing 

Table 1. Biomarkers According to the Type of Cancer

Biomarker Type of Sample Function Use
Breast Cancer
ER/PR (estrogen receptor)/ (progesterone receptor) Tumor tissue Guide treatment Routine testing at time of diagnosis highly recommended, as presence of receptors is associated with response to hormone therapy.
HER2 Tumor tissue Guide treatment Routine testing at time of diagnosis highly recommended, as overexpression of gene is associated with response to specific targeted therapy.
Gene expression analysis Tumor tissue Determine prognosis/guide treatment Testing recommended for distinct population (women with early-stage ER/PR+ cancer with no evidence of disease in the lymph nodes); low risk score indicates that adjuvant chemotherapy will offer minimal benefit.
CA (cancer antigen) 15-3 or CA 27.29 Blood Monitor response May be used in conjunction with diagnostic imaging, history and physical examination.
CEA (carcinoem-bryonic antigen) Blood Monitor response May be used in conjunction with diagnostic imaging, history and physical examination.
uPA (urokinase-type plasminogen activator), PAI-1 Tumor tissue Determine prognosis/guide treatment Testing recommended for newly diagnosed ER/PR+ cancer that has not spread to lymph nodes; low level (low risk) indicates that adjuvant chemotherapy will offer minimal benefit.
Chronic Myeloid Leukemia
BCR-ABL Blood
Aid diagnosis
 
 
Guide treatment
Testing done routinely, as presence of gene is distinguishing feature of the disease.
 
Gene is associated with response to specific targeted therapy.
Colorectal Cancer
CEA Blood
Determine prognosis
 
 
 
 
Monitor response
 
 
 
Detect recurrence/progression
Testing recommended during initial work-up; high level before treatment may indicate cancer is metastatic.
 
 
Biomarker of choice for monitoring metastatic colorectal cancer during chemotherapy.
 
 
Testing recommended during follow-up of nonmetastatic disease to detect recurrence or metastasis.
KRAS Tumor tissue Guide treatment Testing recommended, as over-expression of gene is associated with lack of response to some targeted therapies.
MMR Tumor tissue Determine prognosis Testing recommended; mutation is associated with good prognosis.
Gene expression analysis Tumor tissue Determine prognosis/guide treatment Testing recommended for distinct population (people with stage II disease); low risk score indicates that adjuvant chemotherapy will offer minimal benefit.
Gastrointestinal Stromal Tumor
KIT Tumor Tissue
Aid diagnosis
 
 
Guide treatment
Testing done routinely, as presence of mutation is distinguishing feature of the tumor.
 
Presence of mutation associated with response to specific targeted therapies.
Liver Cancer
AFP (alpha- fetoprotein) Blood
Aid diagnosis
 
 
 
Detect recurrence/progression
Testing recommended at initial work-up; very high levels can indicate liver cancer (but high levels can be increased in other noncancerous conditions).
 
Testing done throughout follow-up if level was initially elevated.
Melanoma
LDH (lactate dehydrogenase) Blood Determine Prognosis Testing recommended at initial work-up, as level is a factor in determining stage of disease. Testing done throughout follow-up of stage IV disease (metastatic melanoma); high level is predictor of poor prognosis.
BRAF Tumor tissue Guide treatment Testing currently done only in clinical trials of targeted therapy for malignant melanoma.
S-100 Blood Detect progression Evidence is currently insufficient to recommend testing, but level is elevated in most individuals with metastatic melanoma.
Multiple Myeloma
Beta-2-microglobulin Blood
Determine prognosis
 
 
Monitor prognosis
Testing recommended at initial work-up, as level is factor in determining stage of disease.
 
Measured throughout follow-up; high level indicates high tumor burden (and poor prognosis).
Nonsmall Cell Lung Cancer
EGFR Tumor tissue Guide treatment Testing is becoming routine, as targeted therapy is more effective when gene is overexpressed.
KRAS Tumor tissue Guide treatment Testing recommended, as over-expression is associated with lack of response to some targeted therapies.
EM4-ALK Tumor tissue Guide treatment Testing has started in some cancer centers, as presence of gene is associated with poor response to some targeted therapies.
Ovarian Cancer
CA-125 Blood
Aid diagnosis
 
 
Detect recurrence/progression
Testing recommended at initial work-up (if symptoms suggest ovarian cancer).
 
Testing done throughout follow-up.
Pancreatic Cancer
CA 19-9 Blood
Determine prognosis
 
 
Monitor response
Testing recommended at initial work-up; high level is associated with poor prognosis
 
Testing done during active treatment for locally advanced metastatic disease; increase in level may indicate recurrence. (Decreased level after surgery or chemotherapy indicates better survival.)
Prostate Cancer
Prostate-specific antigen (PSA) Blood
Screening
 
 
 
Aid diagnosis
 
 
Detect recurrence/progression
Usefulness as screening tool is debated, as the level is elevated in benign conditions of the prostate
 
 
Testing recommended at initial work-up, as level is factor in determining stage of disease.
 
Testing done throughout follow-up.
Testicular Cancer
AFP Blood Aid diagnosis Testing recommended at initial work-up, as level is a factor in determining stage of disease.
hCG (human chorionic gonadotropin) Blood/urine Aid prognosis Testing recommended at initial work-up, as level is a factor in determining stage of disease.
LDH Blood Guide treatment More aggressive treatment is recommended if elevated levels persist.
Thyroid Cancer
Thyroglobulin Blood Detect recurrence/progression Testing done throughout follow-up.

 



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