Does cancer run in families? Will knowing the genetic makeup of a tumor help you treat it more effectively? Genetic screening increasingly being used to answer these questions and gather information to help prevent and treat cancer.
Genetic testing uses blood or a tissue sample to look for changes in genes or chromosomes called mutations. Overall, inherited mutations are thought to play a role in about 10 percent of all cancers, according to the National Cancer Institute, but that percentage can be higher, up to 30 percent, depending on the type of cancer, said Dr. Jeff Boyd, director of genomic medicine at Baptist Health South Florida’s Miami Cancer Institute.
People with a strong family history, those who developed cancer at age 50 or younger, or those with multiple or recurring cancers may be recommended for genetic testing, but having a mutation does not automatically mean you will get cancer, said Dr. Adriana Milillo-Naraine, a breast oncologist at Memorial Cancer Institute.
“There are gray areas. Results can be positive or negative for a mutation, or they may have a gene variation of unknown significance, because we don't have enough information,” she said. Testing may or may not be covered by insurance, depending on the individual.
Meet with genetic counselor
Anyone recommended for genetic testing should first meet with a certified genetic counselor, Milillo-Naraine said. “We look at the risk of having a mutation, do the calculations with a geneticist, then offer a panel of testing that best matches the patient,” she said. “After the results, the patient meets with a counselor again.”
Milillo-Naraine does not recommend home tests. “It's not just doing the test. If you're faced with results, you need to know what to do,” she said. “The pre-counseling and post-counseling is very important.”
Predictive testing is important as a means of prevention, Boyd said, because it can indicate when more aggressive screening, prophylactic surgery or medication is needed. “If we can prevent these cancers from occurring at all, or catch them at an early stage, where they're curable, I think it's very worthwhile,” he said.
Should you screen your children if you feel they are at risk? Dr. Aparna Rajadhyaksha, co-director of Miami Genetic Laboratories at Nicklaus Children's Hospital, said it depends on a family’s circumstances.
“There are certain criteria – such as a family history of cancer that can affect children in their younger years,” she said. For example, one gene that causes colon cancer in adults may cause liver cancer in children 5 and younger. Another syndrome causes leukemia or melanoma in adults, but leukemia or adrenal cortical tumors in children.
“This is important because you need to identify these patients with these syndromes so they can receive appropriate surveillance, and if they have these predispositions to cancer they can be identified earlier, in its most treatable form,” Rajadhyaksha said.
Precision cancer medicine
Genetic screenings also help with treatment.
Over the last 40 years, the National Cancer Institute has funded research to understand what genes cause cancer, said Dr. Jonathan Trent, associate director of clinical research at the University of Miami’s Sylvester Comprehensive Cancer Center. In the last 15 years, specific medications have been developed that target those genes within the cancer — the mutated genes, the genes that the cancer depends on to grow, survive and invade, he said. “In the last couple of years, we've been able to bring these two phenomena together. It's precision cancer medicine,” Trent said.
Genetic testing can be done on a tumor or biopsy from a patient with a metastatic cancer to find which genes are mutated, he said. "We know from laboratory experience if there is a known mutated cancer in a tumor cell, and you treat them with a targeted therapy, you're able to kill that cancer cell,” Trent said. “So the question is, prospectively, can we screen patients, identify mutations and then treat them with this new generation of targeted therapies that go into the tumor cell and leave the normal cells alone?”
Boyd, of Baptist, said the genetic profiles of any two cancers are different. “The idea is you really have to test the DNA of the tumor to see if there are any actionable or ‘druggable’ mutations present,” he said. “That's really the art of precision medicine. It's an evolving field, with new drugs, and new targets being approved.
“Ideally, we like to find targets in every tumor, but it's actually a minority of patients where a ‘druggable’ mutation is found at this moment in time,” Boyd continued. “But that proportion of patients is going to go up and it certainly differs from one tumor type to another.”
At Memorial, Milillo-Naraine said only about 10 percent of breast cancers have a genetic component, so only patients with the highest risk of a genetic mutation are tested. But it can make a difference. With a breast cancer patient, testing results may change the type of surgery done, or identify a clinical trial that addresses a specific mutation, she said.
What cancers are helped by genetic testing?
Testing would not be ordered for a lot of cancers until the patient has recurred or gone through existing standards of care for that type of cancer, Boyd said. But it depends on the cancer type. Patients with non-small cell lung cancer, which has at least three mutations with drugs associated with them that are more effective than traditional chemotherapy, would be tested immediately after diagnosis, he said.
“The point where you would use a test like this depends on where the patient is on the cancer journey, earlier in some, such as lung and pancreatic cancer, and later in others, such as breast and ovary, where there are some pretty effective standards of care,” Boyd said.
Trent said Sylvester Comprehensive Cancer Center has more than 120 clinical trials using targeted therapy. The center’s Molecular Tumor Board looks at a cancer patient’s genetic mutations and tries to match them with a clinical trial that uses a targeted therapy for the genetic abnormalities in their tumor. The center also refers patients to clinical trials around the country, if the patient can travel.
“Almost all of our patients have a mutation,” Trent said. “The question is does knowing the mutation make a difference? Will it change the treatment? Depending on the patient, the best treatment today may still be surgery and radiation. Today, most patients with a primary tumor would not be treated based on their genetic results.” The Molecular Tumor Board meets to determine what's best for the patient — surgery, radiation or a targeted therapy.
“We recommend (genetic testing) for patients whose tumors are advanced in any way — either it can't be resected or there aren't any good therapeutic options,” Trent said. “It can be done on any patient. The question is, is it going to help you give the patient the best therapy possible?”