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Genetic testing can help survivors understand their risk of developing a second cancer, so why aren’t more having this done? By
In 1997, David Dubin began to experience cramping, bloating and blood in his stool. The symptoms — all commonly associated with colon cancer — continued for six months while he tried to persuade his primary care physician to let him see a specialist. It took that long even though there was a family history of the disease; Dubin’s grandfather was diagnosed in his 60s, and his father in his 40s. Dubin was 29 years old.
“It was right there in the chart about my family, but this was the ‘90s and we weren’t thinking about genetics,” he says.
The specialist found stage 3B colon cancer. Dubin underwent surgery that took more than half of his colon, followed by six months of chemotherapy. He was told to get on with his life, but that he should also get a colonoscopy every year.
His doctor told him that his cancer was probably caused by stress, and it was an answer that Dubin could agree with. He had just sold his company, married and had his first child.
Three years later, at age 36, Dubin’s older brother was diagnosed with early stage colon cancer. “It was almost like a rite of passage in my family,” Dubin says.
In 2007, Dubin, then 40, tried to donate blood, but was told that he had a low iron count. Initially unconcerned because he had a colonoscopy the previous year, Dubin decided to follow up with another colonoscopy. A second colon cancer was found. This time stage 2. The subsequent surgery at Mount Sinai Hospital in New York City, left him with 18 inches of colon, which is normally 6 feet long.
After surgery, he met with a genetic counselor at Mount Sinai Genetic Testing Laboratory to be tested for Lynch syndrome, which is caused by a genetic mutation that increases a person’s risk for certain cancers. Up to an 80 percent chance of developing colon cancer. But those with the syndrome are also predisposed to stomach, uterine, pancreatic, bile duct, small intestine, kidney, urinary tract, brain and skin cancers. In addition, women are predisposed to endometrial and ovarian cancer, too.
Lynch syndrome accounts for 2 to 4 percent of colon cancer cases diagnosed in the United States and 2 to 5 percent of endometrial cancers in women. The population with Lynch syndrome generally has early onset disease, and the cancer develops more rapidly. They are also at 50 percent risk of developing a second primary cancer within 15 years.
The test confirmed that Dubin had Lynch syndrome.
Since the mid-90s the number of cancers identified as being caused by genetic mutations has grown dramatically, as well as information about their importance for patients with cancer undergoing treatment. For example, this is when the medical field learned of the BRCA1 and BRCA2 genes, which, when mutated, predispose women and men to breast cancer, and women to ovarian cancer.
In addition to Lynch syndrome and BRCA1 and BRCA2, several other susceptibility genes have been discovered and can now be tested (see sidebar).
Only about 5 to 10 percent of cancers result directly from gene defects inherited from a parent. If a person tests positive, their children have a 50 percent chance of inheriting the mutation.
As the number of identified mutations has grown, so have questions about criteria for genetic testing, as well as who will pay for the tests and how the information will be used.
Genetic tests are usually requested by a person’s doctor or other health care provider when a patient meets the criteria. The tests require a small sample of blood or saliva, which contains cells from inside the cheek or skin cells. The cost for most testing has dropped dramatically from the thousands to the hundreds and, in most cases, health insurance plans will cover the cost when it is recommended by a patient’s doctor.
For those who test positive for genetic mutations, it is then up to them to decide whether to pass that information on to their family members. For at-risk children, learning they are positive at 18 could provide time for lifestyle changes, begin early screening or other considerations to help prevent a cancer. Genetic counselors remind those in counseling that having a mutation does not guarantee a cancer diagnosis.
Available but Not Used
Despite what health care professionals know about genetics and cancer, a study released in February 2017 finds that patients who meet the criteria are still not being offered testing as often as they should be.
Researchers from Stanford University in Stanford, California, surveyed 2,529 women. Of the women considered at average-risk for breast cancer, more than 59 percent said that they wanted genetic testing for germline mutations related to breast cancer risk, nearly 36 percent discussed this with a clinician and 18 percent were tested. Of the high-risk women (773 patients) surveyed, almost 81 percent wanted to be tested, but only 53 percent were.
Heather Hampel, M.S., a licensed genetic counselor in the Clinical Cancer Genetics Program at The Ohio State University Comprehensive Cancer Center in Columbus, Ohio, has studied cancer genetics for more than 20 years and specializes in Lynch syndrome. Hampel says determining if a patient has a genetic mutation will provide much needed information in many areas that could be lifesaving.
“Patients with risk factors for inherited predisposition should know they have a genetic mutation for multiple reasons,” she says. “First, it clarifies what caused their cancer in the first place, and second, it may provide actionable targets for treatment for their cancer and for a second cancer, should it occur.”
Hampel offers the example of a young man that she tested who was coming in at the behest of his father, who was diagnosed 10 years earlier with colon cancer when his son and daughter were still young children. The father had tested positive for Lynch syndrome and knowing that his children were at 50 percent risk of inheriting it as well he planned to have them tested after they turned 18.
The son did have Lynch syndrome, Hampel said, and, at age 24, he already had early stage colon cancer, which was removed. “He kept saying that we saved his life,” Hampel recalls. “His sister came in the next week and testing showed that she was negative.”
While the sister was in the office she began to tell Hampel about her father, who had done well for the decade since his diagnosis, but was now dealing with stomach cancer. “I talked to her about a new immune therapy for those with Lynch syndrome and she said she would discuss it with him,” says Hampel. “His doctor didn’t know about it, but after finding out about it they began the therapy immediately.”
Hampel says the man is responding well to immunotherapy and, while there is no idea how long it will last, research has shown some durable remissions. “It is the perfect full circle of how being tested can help the children,” she says. “Even though our patient was doing everything right, he developed another cancer, but we were able to help in terms of treatment.”
In Dubin’s case, he continues to get an annual colonoscopy and receives thorough screening in other areas that may be predisposed to cancer because of Lynch syndrome. In 2009, scans revealed a small malignant tumor on his kidney, which was removed.
The three-time cancer survivor has three sons, who were too young at the time of his diagnosis to be tested for Lynch syndrome. His oldest son, now 21, tested positive for Lynch syndrome at 18, and, like Dubin, is monitored closely with an annual colonoscopy and other scans. Dubin plans to encourage his two younger sons to be tested when they are 18.
After his second diagnosis, Dubin established a nonprofit organization called AliveAndKickn, http://aliveandkickn. org, to educate and provide support for those who carry the Lynch mutation as well as physicians. He meets with physicians, hospitals and individuals to provide a range of services.
Dubin says the shortage of genetic counselors and the ongoing belief that testing is still very expensive and insurance won’t pay for it keeps physicians and patients alike from discussing it.
“Physicians may not be up on all of the information and don’t always have time in the day to be fully versed on something new such as genetics,” says Dubin. “They are doing a disservice to their patients, but it’s hard to change their ways.”
Through AliveAndKickn, he has also created a clinical education program that trains physicians to know what to look for in young patients with colon cancer since Lynch syndrome often means early onset.
In addition, Dubin created the country’s first registry for patients with Lynch syndrome, the HEROIC registry, which allows patients to contribute medical information and their experiences living with Lynch syndrome and its associated cancers to help researchers develop new treatments, understand the various Lynch genetic mutations, write medical papers and conduct further studies and clinical trials.
“As an organization, we have made it a point not to reinvent the wheel,” he says. “There was no registry before, and the responses have been overwhelmingly positive. Hospitals are now looking at incorporating it into their work with survivors who come back as Lynch positive.”
Dubin’s advocacy work led him to a job offer from Mount Sinai Health System in New York in 2015 as the director of sales for the same lab that tested him for Lynch syndrome. He works to educate physicians and provide the most up-to-date genetic screening for hospitals around the country.
Testing Pros and Cons
Mary Daly, M.D., Ph.D., a medical oncologist at Fox Chase Cancer Center in Philadelphia, specializes in treating women with breast cancer, having established one of the first cancer risk assessment programs in the country in 1991 at Fox Chase.
She provides genetic counseling for anyone considering testing to help them understand their options and how their family history can impact those decisions.
Daly has watched as testing for one genetic mutation has grown into testing for numerous mutations in one test called multigene panel testing. The test simultaneously examines many genes to look for potentially cancer-causing mutations.
“We have panels now that allow a much broader look at possible mutations,” she says. The family history may indicate a much larger panel or repeated testing, adds Daly.
Identifying if a patient is positive for a genetic mutation that can lead to cancer can provide time to take preventive measures, such as screening, prophylactic surgery or lifestyle changes.
Daly notes that not all patients who test positive get cancer. But for many women with BRCA1 or BRCA2 they have turned to prophylactic surgery — most waiting until they have had children. For others, the challenge may be to decide whether to have children, since they will have a 50 percent probability of having the mutation.
A negative genetic result can be reassuring, but Daly says it’s important to accept that being negative also does not guarantee a cancer will not occur. Speaking with a genetic counselor can help the patient make a careful family history that may clarify their risk.
The most frustrating result of testing may be what is called a “variant of uncertain significance,” Hampel says. This is when the test finds a genetic change, but it is unknown if it is a normal human variant or one that increases cancer risk. Over time the change may be identified as one that will increase risk, or not. With panel testing, the odds of finding a variant of uncertain significance is higher.
Hampel also points out that for patients who had genetic testing done as the research was first emerging in the mid-90s, and tested negative, that they may want to be retested.
“Some people who were tested years ago need to get tested again because it was not as complete,” says Hampel. “We can do multigene panels today that are less expensive and look for multiple genes.” A multipanel test for the most common cancers can now be found for under $300, adds Hampel.
As to his own health and that of his family, Dubin says his grandfather and father both died of other causes than cancer. Dubin says living with only 18 inches of colon has not slowed him down. The highlight of his week: playing soccer and coaching with a local team.