Cancer Treatment Centers of America

Family matters: Genetic testing for inherited cancer syndromes

Author: Barbara Boughton

Cindy Aguilar, 55, of Las Vegas, Nevada, had always known that breast cancer ran in her family: her mother had died of the disease at age 47, two aunts had also been diagnosed, and her grandmother died of it at age 55. After Cindy herself was diagnosed with breast cancer in Las Vegas, she went to Cancer Treatment Centers of America® (CTCA) in Goodyear, Arizona, in 2011, where she felt the need to undergo genetic testing. The result of the test was positive, showing that Cindy had an inherited breast cancer syndrome caused by a mutation in the BRCA1 gene.

The result of the genetic test compelled Cindy to have a double mastectomy, which could improve her chance of avoiding a recurrence. “I was expecting that the test would be positive because of my family history,” she says, “but getting the test enabled me to decide on the best course of treatment.” Cindy’s experience speaks to the potential benefit that genetic testing can provide, but it’s not always an easy choice to make, and families often grapple with the potential for emotional and physical change that testing can bring.

Inherited cancer syndromes

Inherited cancer syndromes are caused by mutations (abnormal changes) in genes that control cell growth and DNA repair and are passed down genetically from generation to generation. An inherited cancer syndrome can result in diagnoses of cancer for multiple family members and can mean an increased risk for several different kinds of cancer.

Hereditary breast and ovarian cancers are caused by mutations in the BRCA1 and BRCA2 genes, which can confer up to an 85 percent risk of developing breast cancer and increase risks for other cancers, such as those of the ovaries, prostate, and pancreas. Lynch syndrome is another inherited cancer syndrome, which is caused by a mutation in one of five genes that monitor and repair genetic errors that occur in the cells. Individuals with Lynch syndrome have an increased risk for colon and endometrial cancer as well as other cancers, including those of the stomach, ovaries, and brain.

Li-Fraumeni syndrome is an inherited cancer condition that results in an elevated risk for leukemia and cancers of the breast, brain, and adrenal glands as well as a type of cancer called sarcoma, which can occur in bone, muscle, cartilage, and other connective tissues. Familial adenomatous polyposis is an inherited syndrome in which people form tens to thousands of precancerous polyps in the colon and which also confers an increased risk for cancers of the small intestine, thyroid, and liver.

Multiple cases of cancer in an immediate or extended family do not always indicate an inherited syndrome, however. The red flags that may indicate an inherited cancer syndrome include: cancers diagnosed in individuals younger than age 50; multiple individuals in a family diagnosed with the same or related cancers; multiple cancers in the same person; cancers that are rare, such as breast cancer in men; and eastern European (Ashkenazi Jewish) ancestry in families with breast or ovarian cancer.

Testing facts

According to Eric Fowler, MS, a certified genetic counselor and manager of genetic counseling at CTCA in Zion, Illinois, a genetic test for cancer syndromes can have four different results: positive, indeterminate, negative, or inconclusive. A positive result means that a genetic change—a mutation—was discovered that increases cancer risk; an indeterminate result means no mutation was discovered and it’s unknown why the cancer occurred in an individual and a family; a negative result means that an individual does not carry a mutation previously identified in another family member; and an inconclusive result is one in which a genetic variation is found that may or may not affect cancer risk. It’s important to note, however, that genetic testing may not always be definitive, Fowler adds. Some people who clearly have a hereditary cancer risk may not have a mutation in a gene that has been identified, or they may have a mutation that is undetectable with current genetic-testing technology.

This was the case in Reagan Barnett’s family. Fourteen members of Reagan’s extended family had been diagnosed with colon cancer, and she was diagnosed and treated for the disease in 2008 at age 22. Despite the high prevalence of cancer in her family, when Reagan underwent genetic testing the results were negative for Lynch syndrome, which confers a greatly increased risk for colon cancer. Earlier laboratory testing on the tumor taken from Reagan’s colon, however, indicated a “loss of expression” in two of four different proteins produced by the genes that cause Lynch syndrome. “So altogether, the test results indicate that my family has a Lynch syndrome (or genetic mutation) that hasn’t been discovered yet,” says Reagan, who blogs about cancer issues and is studying for her doctoral degree in medical sciences at the University of South Alabama.

Family matters

The benefits of genetic testing for patients who test positive are considerable. If an inherited cancer syndrome is detected, there are often preventive measures—including increased screening, prophylactic surgeries, and medications—that can help reduce the risk of cancer or of recurrence. Testing is also a complex decision, however, with potentially far-reaching consequences.

Because inherited cancer syndromes often affect multiple members of a family, getting a positive test result can have meaning not only for the individual who is tested but also for the extended family. A positive result can mean that other family members have an inherited cancer syndrome, too, and are therefore at increased risk for cancer. This information can lead to potentially lifesaving preventive measures, but the scenario can also bring on emotional challenges as families cope with anxiety over whether to be tested and the implications of those results.

In Cindy Aguilar’s case, testing resulted in conversations with her daughter, age 31, and her son, 37, who both decided to undergo genetic testing. The increased cancer risk conferred by BRCA1/2 mutations can affect both men and women: men may get breast cancer or other cancers associated with these syndromes and can also pass the mutation on to their children.

“I told my daughter: ‘I think you need to have the genetic test for BRCA1 done, but it’s your choice and your body,’” Cindy says. “When I spoke to my daughter, I said that if she didn’t get the genetic test, she might worry about it for the rest of her life—but she had to make the decision for herself,” Cindy adds.

As Cindy’s story illustrates, the decision to be tested for a genetic or inherited cancer can mean sitting down and talking about whether testing for an inherited cancer syndrome is right for all family members. Those who go through with testing often do so with the idea that knowing that they have an inherited cancer syndrome will allow them to make decisions about their health care—whether to undergo morefrequent screenings or take preventive measures, according to Fowler. In addition, when a person is tested for an inherited cancer syndrome and the result is positive, “Sometimes he or she has a sense of relief, finally having an answer for why so many cancers occurred in the family,” Fowler says.

Robin Colgrove decided to undergo genetic testing after she was diagnosed with stage IV breast cancer in 2006. There were many cases of cancer in her family: her paternal aunt had previously tested positive for a BRCA1 mutation, and her sister had previously tested positive for a mutation in the BRCA2 gene. “My sister and I had a really good talk about whether to have the genetic test. We decided that after her positive test results it was important for me to get tested, too, so we could have the full picture,” says Robin, 50, who lives in Spearfish, South Dakota, and was treated at CTCA in Zion.

Robin did test positive for an inherited breast cancer syndrome, but not the BRCA2 mutation that affected her sister. She was positive for the BRCA1 mutation, which was inherited from her father’s side of the family. It was later determined that her mother had the BRCA2 mutation found in her sister. It is very unusual for there to be two mutations in the same family; most families with inherited cancer syndromes test positive for only one mutation.

“Getting genetic testing helped me as well as members of my family by giving us information so we can do as much as possible to prevent cancer,” Robin says. “Now we all know what we are facing, instead of worrying and just waiting for the other shoe to drop.”

Not all people are emotionally ready to take a genetic test for a cancer syndrome, however; a positive result may cause worry and anxiety, so they may decide not to be tested, Fowler says. In other cases, insufficient health insurance or no coverage for cancer screenings or preventive medications and procedures may keep family members from following through with testing, he adds.

Each family is unique

Ultimately, each individual and each family will make their own decisions about genetic testing based on their unique perspective. “After I had the genetic test, some of my extended family members were very receptive and interested in learning about Lynch syndrome,” says Reagan Barnett. “One of my cousins went through genetic testing, and others have implemented morefrequent colon screenings—just in case they have the mutation. Others just were adamant: they did not want to know if they had the mutation.”

Whichever choice an individual or family makes, there is no doubt that the increasingly accessible information about inherited cancer syndromes is propelling cancer prevention and treatment forward and inspiring important conversations among family members.