February 9, 2010
What Good Are Cancer Tests Anyway?
Cancer tests can help oncologists, pathologists, and most importantly patients in the following ways:
- Diagnosis of tumor type
- Guiding treatment
- Determining prognosis
- Monitoring response to treatment
- Assessing for hereditary predisposition to cancer
Diagnosis
Cancer tests are sometimes needed to help determine the correct diagnosis for a tumor type. Different types of cancer have different treatments and prognoses. Consequently, knowing the correct tumor type helps an oncologist or other physician know how to treat the tumor and to have a feel for her/his patient’s prognosis. Examples of tests that may aid in the diagnosis of certain tumors are FISH (fluorescence in situ hybridization) and RT-PCR. These tests can be used to identify chromosomal translocation that are specific for certain types of tumor. A number of hematologic malignancies (e.g. chronic myelogenous leukemia, follicular lymphoma, and mantle cell lymphoma) and sarcomas (e.g. synovial sarcoma, Ewing’s sarcoma) are characterizied by chromosomal translocations that are specific for those tumors. Ewing’s sarcoma tumor cells for instance almost always carry a t(11;22) translocation. If a pathologist is having difficulty making a diagnosis of one of these tumor types based on morphology (i.e. microscopic examination) alone then a FISH or an RT-PCR test that identifies the particular translocation characteristic of that tumor can help confirm the diagnosis.
Guiding Treatment
Some cancer tests are used by oncologists to determine if a particular drug is likely to be effective. For example, about 20-25% of breast cancers exhibit amplification of an oncogene known as the HER2 oncogene. This leads to increased amounts of the Her2 protein on the surface of these tumor cells (Her2 overexpression). A drug known as Herceptin which is an antibody to the Her2 protein has been developed to specifically target tumor cells that overexpress the Her2 protein and studies have shown that Herceptin is significantly more effective for women whose breast cancer overexpresses Her2 than for women whose breast cancer does not overexpress Her2. But Herceptin is very expensive. It can cost anywhere from $50,000 to $100,000 per year. Consequently, a relatively inexpensive laboratory test (~$500-$1000) that can predict which women are most likely to benefit from this expensive drug is quite useful. The two tests that are most often used are immunohistochemistry for Her2 overexpression and FISH for HER gene amplification. The measurement of estrogen (ER) and progesterone (PR) receptor expression in breast cancer is another example of a test that is widely used to guide breast cancer therapy. Women that express ER and/or PR generally respond to tamoxifen, a drug that binds and blocks signaling from these receptors. These tests are examples of a type of test that is referred to as a cancer pharmacogenetic test.
Determining Prognosis
Some tests are used to determine a patients prognosis. A good example of such a test is the OncotypeDx test offered by Genomic Health (Note: I do not have any financial relationship with this company). This test measures the level of expression of approximately 20 different genes in a woman’s breast cancer. A number of clinical trials have shown that a certain pattern of expression of these genes detected by this test predicts which women are most likely to experience breast cancer recurrence. Thus this testing can be used to identify which women have a poorer prognosis and should receive additional chemotherapy. Other tests that can be used to assess prognosis include markers that assess how rapidly a tumor is proliferating (e.g. Ki-67 for breast cancer) or assess the cytogenetic abnormalities present in a tumor (e.g. karyotyping of childhood ALL).
Monitoring
Some tests are used to determine if a tumor has responded to therapy and remained in remission. A good example of such a test is the prostate specific antigen (PSA) test. This test measures the levels of the PSA protein in the bloodstream. Prostatic epithelial cells express PSA. Normally PSA is confined to the prostate but in men with invasive prostate cancer PSA can escape the prostate and enter the bloodstream. This leads to elevated levels of PSA in the bloodstream. Prostatectomy is generally accompanied by a drop of PSA serum levels but rising levels generally herald tumor recurrence and spread to distant sites such as the bone.
Assessing for Hereditary Predisposition to Cancer
The single best way to reduce cancer deaths is to detect tumors early and eradicate them before they become dangerous. Breast, cervical, colorectal and prostate cancer screening have led to reduced mortality rates for each of these tumors over the past several decades. This is because screening generally leads to detection of tumors at earlier and more curable stages. Some individuals carry mutations in a class of genes that predispose them to the development of certain cancers. For example, 2-3% of individuals who develop colorectal cancer carry mutations in one of four or more DNA mismatch repair genes. This hereditary disorder is known as hereditary nonpolyposis colorectal cancer (HNPCC). Individuals with HNPCC are predisposed to the development of colorectal cancer and other tumor types such as endometrial cancer (women), gastric cancer, and upper urinary tract urothelial carcinoma. Individuals with HNPCC tend to get these tumors at a younger age than individuals with sporadic cancer of the same type. For example, the average age at diagnosis of colorectal cancer for HNPCC is in their 40′s as compared to an average age of sporadic colorectal cancer being in the early 60′s. Tests that identify patients with hereditary cancer syndromes such as HNPCC allow physicians to initiate early regular cancer surveillance of these patients so that any tumors that develop in these patients are more likely to be detected at early and curable stages. Some studies have shown that this strategy is indeed effective at reducing mortality in these patients.
Collectively, cancer tests help oncologists more effectively and economically treat cancer patients.
