Genetic Testing and Cancer

A basic understanding of genetics is fundamental to treating cancer, and scientists and medical professionals are always learning more. At its core, cancer is a genetic disorder. Most cancers are caused when small changes, known as mutations, occur in our cells’ normal DNA (deoxyribonucleic acid). The causes of these mutations are all around us, from cancer-causing agents in our environment to radiation constantly bombarding us from space. Our cells have machinery in place to search out and correct these mutations, and usually they are pretty good at catching them all. However, if the mutations are passed along to the next generation of cells, they can accumulate over the years. Occasionally, the genes that contain the blueprints for the DNA-repair machinery are damaged themselves, allowing mutations to accelerate. When enough genes mutate, the cells stop behaving like normal cells should and can become cancerous.

Given that genetics lies at the heart of cancer, often genetic testing can provide useful information in making decisions about treatment. As a physician who treats cancer, I think mainly of three types of genetic testing that can impact the care of my patients. All three major types of genetic testing are available to cancer patients at the Southwestern Vermont Medical Center.

The first type of genetic testing is germline testing. With the assistance of professional genetic counselors, we take a sample of a patient’s DNA and review the genes that make the patient who she or he is. These are the genes that the patient inherited from their parents, and sometimes, they can include mutations that run in the family. This leaves some patients more susceptible to cancer than others.

I often recommend germline testing for patients who have a strong cancer history in their family, who get cancer at a very young age, or who have a personal history of multiple cancer diagnoses. Finding out if they inherited some of their cancer susceptibility from their parents can mean that patients need to be extra vigilant in screening for additional cancers or start screening at a younger age. Some patients will opt to have preemptive treatment, such as a “double mastectomy” for patients with a very high breast cancer risk. Finally, those with inherited mutations can encourage close family members to undergo testing themselves.  Only 5-10 percent of all cancers are related to inherited gene mutations that we can test for, but knowing may help patients or those they love make important decisions about the course of their treatment.

Here at SVMC, we cooperate with a genetic counselor from Dartmouth-Hitchcock’s Genetic Counseling practice. Patients can meet the genetic counselor via telemedicine, and if testing is recommended, their sample can generally be obtained here.

For many patients, testing the genes of the whole patient isn’t warranted, but testing of the genes of the tumor itself is. In many cases, the tumor’s genetic information can help to narrow a diagnosis and determine the best treatment. When cancer is suspected, most patients undergo a sampling of the suspicious tissue known as a biopsy. Different types of cancers can look very similar under the microscope, but their specific mutation profile enables us to tell them apart. Sometimes those mutations themselves provide a target for cancer treatment.

For instance, there are many types of leukemia that are difficult to treat. But one type in particular, known as CML, includes a mutation that can be targeted with a drug called Imatinib (Gleevec). The drug targets only cells with the specific cancer-causing mutation and thus preferentially kills off only the leukemia cells. It leaves the rest of the patient’s cells alone, which means the cancer is controlled with very few side effects. This treatment is successful in more than 90 percent of patients. Scientists worldwide are working to make similar discoveries and replicate these results for more cancer types.

Finally, we also test the genes being expressed by cancer cells. In other words, we test, not just which blueprints they have access to, but the ones they are using to build with. For instance, a test called an Oncotype DX looks at the RNA (ribonucleic acid) of 21 different genes in breast cancer cells. The test tells us which genes are being transcribed from DNA into RNA—the gene expression profile— which gives us information about how aggressively that patient’s cancer is expected to behave. Even if we don’t have a targeted therapy tailored to those specific genes, we can still personalize treatment using conventional cancer therapies, such as chemotherapy and radiation. A patient with a low Oncotype DX score is less likely to benefit from chemo than a patient with a higher score. The patient can reasonably avoid much of the toxicity involved with more aggressive treatment.

Genetic testing won’t be the best course of action for every cancer patient. Tests are limited in some ways, and the results won’t always be helpful. Talking to your doctor or genetic counselor about the benefits and potential drawbacks is the best way to decide if genetic testing is right for you.

Dr. Matthew Vernon is a radiation oncologist at the Southwestern Vermont Regional Cancer Center, which is a part of the Southwestern Vermont Medical Center and Southwestern Vermont Health Care.