Inherited Risk: Genetic Testing Can Bring Answers, and New Questions

Emily Bakaj, of Philadelphia, was diagnosed with stage II breast cancer in October 2009 at 51 years old. The age had unsettling connections for Emily: Her mother died of breast cancer and was also diagnosed at 51.

Emily’s family history — along with her mom, a great-aunt had the disease — and her Ashkenazi Jewish heritage pushed her doctors to recommend genetic testing, which searches DNA for a mutation, or error, that increases the risk of developing a disease, like breast cancer.

Most cancers are caused by mutations that happen during a person’s life. But some mutations  pass from parent to child and put people at higher risk for breast cancer. You have a 50 percent chance of inheriting a mutation if one of your parents is a carrier. An estimated 5 to 10 percent of breast cancers are linked to mutations on the most well-known breast cancer-associated genes, the BRCA genes.

The overall risk of a woman in the U.S. getting breast cancer in her lifetime is 12 percent. But the National Cancer Institute reports that women with a BRCA1 mutation have a 55 to 65 percent chance of developing breast cancer by age 70. Women with a BRCA2 mutation have a 45 percent chance. These mutations, especially BRCA1, also raise the risk of ovarian cancer. They raise breast cancer risk in men, though to a much smaller degree than in women. BRCA mutations are not very common in general: Some researchers estimate about 1 in 800 people in the U.S. have one. But people in some ethnic groups are more likely to carry them. For example, in the U.S. about 1 in 40 Ashkenazi Jews carries a BRCA mutation.

Emily waited for the test results before deciding which breast cancer surgery to have. Women with a genetic mutation have a high risk of a new cancer forming, so they often remove the affected breast and get a prophylactic, or preventive, mastectomy to remove the unaffected breast and prevent future cancer. They may also get a prophylactic oophorectomy, surgery that removes the ovaries, to prevent ovarian cancer.

Emily’s test results arrived quickly, and despite her family history, tests did not find any mutations known to raise breast cancer risk. Doctors told her she may carry a mutation researchers have not yet identified, or she may not have inherited a higher risk of breast cancer.

“At that point, I wanted someone to be able to say, ‘You have the gene [mutation] so get the mastectomy,’ or, ‘You don’t have the gene [mutation] so you don’t need to have a mastectomy.’ But instead I received the question mark,” Emily says. “I still had to make a decision. I really wanted that taken out of my hands.”

‘Information Is Power’

Knowing if you carry a gene mutation can help not only you, but also your family, according to Mary B. Daly, MD, PhD, FACP. Dr. Daly is the chair of the Department of Clinical Genetics at Fox Chase Cancer Center, in Philadelphia.

If tests show you carry a gene mutation that increases breast cancer risk, relatives may look into genetic counseling to see if they carry it, too. Some may find it difficult to hear they have a higher risk for breast cancer. But if they choose to test, the results can inform their future health decisions.

Most genetic tests require a cheek swab or a blood sample. In a cheek-swab test, your doctor rolls a cotton-tipped swab along the inside of your cheek. For a blood sample, the doctor uses a needle to draw a small sample of blood, usually from a vein on the inside of your arm.

There are different kinds of tests and different companies that offer them. Some look for evidence of any mutations of one specific gene, like BRCA1. Others look for a single, specific mutation of a specific gene, if that mutation has been found in a family member. Others test a wide panel of genes and possible mutations.

Even without the definite answer she hoped for, Emily thinks genetic testing is important. “I found the process to be very illuminating,” she says. “I always felt that information is power. The more information that I had, the better to make my treatment decisions.”

Genetic Counseling

If you are interested in genetic testing, it’s best to do it soon after your diagnosis, Dr. Daly says. Many people, like Emily, wait for results before deciding on surgery. For this reason, many providers ask questions early in the process to see if you should meet with a genetic counselor. But even if you don’t get genetic testing right away, you can still be tested, even years later.

Before you meet with a genetic counselor, try to collect information on your family’s health history. Your genetic counselor reviews the history with you and looks for patterns that might signal a particular gene mutation, according to Dr. Daly. They also consider things like a past diagnosis of breast or ovarian cancer, diagnosis with breast cancer before age 45, diagnosis of triple-negative breast cancer, and certain ethnic backgrounds. This helps your doctors choose the right genetic test for you. Which tests or testing companies your health insurance covers may be part of that decision, too.

When test results come in, the genetic counselor tells you what different results can mean and what your treatment options are. Many labs return results quickly when they will be used in treatment decisions, Dr. Daly says, so you may know in about a week. On the longer side, results can take 2 to 3 weeks.

Most people learn they do not have a genetic mutation related to cancer risk. Dr. Daly says the results identify a mutation in about 10 to 20 percent of people who get genetic testing. Even if you are found to have a mutation, that does not mean you will definitely get a second breast cancer. But you will be able to make informed treatment decisions.

‘I Had No Fear’

Susan Rosen, 52, of Franklin, Massachusetts, did not know of anyone in her family with breast cancer when she was diagnosed with stage III, hormone receptor-positive disease in 2010. Still, her doctors recommended she meet with a genetic counselor.

Susan was just 45 at diagnosis, and like Emily, her family is of Ashkenazi Jewish descent. Susan’s test came back positive for a BRCA2 mutation. She had a lumpectomy, then radiation and chemotherapy. Because of the genetic mutation, Susan also had an oophorectomy.

Susan’s oldest sister tested positive for a BRCA2 mutation as  well, but another sister did not. The affected sister had an oophorectomy and gets screened for breast cancer more often because of the high risk.

In 2013, Susan’s doctors found the cancer was now stage IV, or metastatic, and the BRCA2 mutation again affected her treatment decisions. She received a PARP inhibitor, a medicine that stops an enzyme in the body, called PARP, from repairing damaged DNA in cancer cells.

In Susan’s case, the cancer did not respond to the PARP inhibitor. Still, she says knowing about the gene mutation allowed her and her family to take action and try new treatment options.

“I know some people are afraid to go get tested but it didn’t bother me at all. I had no fear. I live now. If there’s something I can’t change, I don’t worry about it,” Susan says.

Moving Fast

Researchers have recently identified and can now test for more mutations linked to higher-than-average risk for breast cancer.

Genes that can carry those mutations include PALB2, ATM, CDH1, CHEK2, PTEN, STK11 and TP53. These generally aren’t as common as the BRCA mutations, don’t increase the risk of breast cancer as much, or both. Like the BRCA mutations, these mutations usually involve a problem in the instructions genes use to tell the body to stop making new cells. Treatment guidelines are different for the various gene mutations as each comes with its own level of breast cancer risk and in some cases raises the risk of other conditions, too. Discuss results with your medical team to learn about your treatment options.

As the genetics field has grown, so has awareness. Actress Angelina Jolie publicly announced in 2013 that she carried a mutation on the BRCA1 gene and had a prophylactic double mastectomy. Though she had not been diagnosed with breast cancer, her mother died of ovarian cancer, which is also linked to BRCA gene mutations. Two years later, Ms. Jolie also had a bilateral oophorectomy. Media coverage of her operations was the first time many people heard of these gene mutations.

Other important news about genetic testing has not been so widely discussed. One example is the American College of Surgeons making a genetic testing program a requirement for its hospital accreditation. Dr. Daly says this leads to more doctors being aware the information is available and more people having a path to testing. Another example is the Supreme Court ruling that human genes could not be patented, which allowed more companies to offer genetic testing. This made tests easier to access and less expensive.

Still, not all providers have deep knowledge of breast cancer gene mutations. Dr. Daly says if you have some of the features associated with a genetic mutation, tell your doctor and ask if you should speak with a genetic counselor.