Knowledge is Power: Genetic counseling and testing can arm you with information to fight cancer
June 25, 2016
Mandy Waldorf Graham felt she had been stalked by cancer since her early adolescence. Her mother was obsessed by it because all the women in her family—her mother, grandmother and aunts—were stricken with the dreaded disease by the time they hit age 50. Then when Mandy was in college, her older sister was diagnosed with a cancer of unknown origin and died less than 11 months later at age 32.
“I had this looming fear,” says the 38-year-old Los Angeles-based advertising executive. “And my mother expected that any day she would find out she had cancer too.”
But Mandy pushed her worries into the back of her mind because she didn’t think there was anything she could do about it. She didn’t become more proactive until after the birth of her third child 1½ years ago, when she went to see a new gynecologist. Given her family history, the doctor suggested that she get tested for the presence of genetic mutations that would greatly heighten her risks for developing cancer.
The test did, in fact, reveal precisely what she feared: She was positive for BRCA2, a mutant gene that indicated she had an 85% chance of developing breast cancer, and her odds for ovarian and pancreatic cancer were also much higher.
“Although the test results confirmed my fears, the result itself was relief. It was no longer an irrational or mysterious fear; it was grounded in truth.” – Mandy Waldorf Graham
“All of a sudden everything got very serious,” says Mandy, who subsequently underwent a battery of tests, including an MRI and an ultrasound of her ovaries, to make sure she didn’t already have cancer. “Although the test results confirmed my fears, the result itself was a relief. It was no longer an irrational or mysterious fear; it was grounded in truth. Now my doctors and insurance company would take me seriously if anything suspicious popped up. That is not what happened when my sister started feeling sick and consulted with doctors. It took much too long before someone took her seriously enough to consider cancer at age 31.”
Mandy was referred to Richard Frieder, MD, an assistant professor of clinical cancer genetics and a specialist in cancer risk assessment at the John Wayne Cancer Institute and a physician at Saint John’s Health Center, who outlined her options. They ranged from simply doing intensive surveillance in order to detect any possible cancers at their earliest stages to the more aggressive steps of mastectomies with breast implants and reconstruction along with removal of her ovaries and fallopian tubes so the cancers wouldn’t have a place to take root.
Taking preventive measures can greatly reduce risk. Removing the ovaries and tubes along with hormone replacement can curb the 45% lifetime risk of ovarian cancer down to less than 2%. Using modern cosmetic techniques to perform preventive mastectomy brings the breast cancer odds down to less than 5%. Both surgeries represent life-changing and lifesaving care for women with these high-risk genes.
Mandy did some intensive research on her own so she could make an informed decision. Based on that, she decided to go ahead with a bilateral mastectomy because she felt that breast cancer was more of a threat. She chose to put off the ovarian surgery for a few years.
“The mastectomy seemed like a good first step,” says Mandy, who underwent the surgery along with breast reconstruction earlier this year. “It feels a little weird, and it has changed my body forever. But I need to take care of myself—for myself and for my family.”
Since then other family members have been tested, and one of her brothers and his oldest daughter, who’s 21, both have the BRCA mutation. “Getting the test is the simple part. But what happens when you see the results is when it becomes more difficult.”
We’ve all known families who have cancer, where it seems like it strikes one generation after another. It may even be true in our own families. But how do we know when there truly is a family history of cancers which indicates that these malignancies are inherited and caused by mutations in our DNA, or when they’re just a product of the environment, bad luck and unknown causes?
“Most breast cancers are found in women without known risk factors, though both personal and family histories may make a woman more susceptible,” says Dr. Frieder. “About 10% of breast cancers are related to BRCA and other ‘broken’ inherited genes, which are then influenced by environmental triggers and may even be increased or decreased by other genetic mutations.”
“Testing enables people to take control, maximize their wellness and oftentimes changes their destinies. This isn’t bad news, but a gift.” – Dr. Richard Frieder
In general, up to 20% of all cancers may have an identifiable hereditary susceptibility, and both high-risk as well as low-risk men and women can be helped by preventive care, risk reduction and cancer prevention.
“Testing enables people to take control, maximize their wellness and oftentimes changes their destinies,” says Dr. Frieder. “This isn’t bad news, but a gift. Finding out you have a genetic predisposition but that most of that cancer is preventable is good news.”
WHO SHOULD GET TESTED
People are candidates for genetic testing for cancer if there is a strong family history of cancer. That’s why it’s important to talk to family members to find out what type of cancers relatives had and at what ages they were diagnosed and subsequently died.
In about 10 of the most common cancers, genetics seem to play a role, including breast, pancreatic, ovarian, stomach, uterine, colon, thyroid, kidney and adrenal cancers. Experts say to look for patterns that would indicate there is a strong hereditary component. These red flags include: early age of onset, such as breast or colon cancer before the age of 40 or prostate cancer before age 50; family members with multiple cancers or cancers in paired organs (both breasts or both kidneys); or multiple people in the family having the same form of cancer.
There are also what are called linked cancers, which means cancers that may seem dissimilar but are usually caused by the same genetic mutation, such as pancreatic and melanoma, breast and ovarian, breast and colon, colon and bladder, and thyroid and adrenal. A genetic condition called Lynch Syndrome, for example, causes a range of seemingly unrelated cancers in both men and women. If there is a high incidence of these cancer pairings or people in your family get different types of cancers, that may also be a tip-off.
Certain endocrine cancers, such as neuroendocrine tumors, also have a high genetic component. Surgery is not the only option to prevent a late-stage cancer diagnosis. In some cases, preventive medications can be taken or individuals can be screened or followed closely by their doctors. In fact, for those who have the BRCA mutation, insurers must pay for annual breast MRIs.
Even if you already have cancer, these tests can help. “Understanding that someone has a genetic predisposition will change their management and treatment plan, as well as possibly prevent a second cancer,” says Dr. Frieder.
Positive genetic tests may also open the option of using a highly effective new chemotherapy, such as Lynparza, which works specifically on BRCA-positive ovarian cancers by focusing the attack on these molecular flaws. It may change the way radiation is used or suggest that more invasive surgery would be better.
WHAT TESTS ARE AVAILABLE
The good news is that there is multi-panel testing for hereditary cancer susceptibility, which can identify an array of errant genes that have been linked to cancer (see box).
But now there’s been an explosion in genetic testing, which has greatly increased access. Moreover, costs have dropped dramatically from a high of $4,000 for BRCA tests to a more palatable $475 for up to 19 genes. Under the guidelines of the Affordable Care Act, insurers have to pay for these tests when a family history indicates it’s appropriate.
If you’re concerned, see a genetic specialist. There is a shortage of genetic counselors—nationwide, there are only about 500. But Saint John’s Health Center has specialists on staff to help you evaluate your risks. The Cancer Prevention Clinic at the Margie Petersen Breast Center at Saint John’s can also help people understand their risks and provide them with resources.
KNOW YOUR RISK
Genetic counseling can help you figure out or evaluate your general cancer risk: low, medium or high. Testing will provide you with more specific information.
- Low or sporadic risk means that someone doesn’t have any of the obvious risk factors, but cancer can still strike.
- Medium—or familial or personal—risk is someone with a family or personal history of risk factors.
- High risk means that a patient has one or more of the errant genes, like BRCA1 and BRCA2, which are strongly linked to cancers.
THE NEW GENE TESTS
“It used to be that if we didn’t find any BRCA mutations, we wouldn’t look further,” says Dr. Ora Gordon, a professor of genetics at the John Wayne Cancer Institute. “But now we have such a broad toolbox of things we can look for. There are about 25 different genes that have been identified that are linked to cancers.”
Here are some common genetic mutations these tests can identify:
- Hereditary breast cancer and ovarian cancer syndromes (genes: BRCA1, BRCA2) linked to these and other cancers, including prostate, pancreatic and male breast cancer
- Lynch syndrome (genes: MSH2, MSH6, PMS2, EPCAM) linked to an increased risk of a range of cancers such as colorectal, liver, renal, brain and, in women, ovarian, uterine and endometrial (which is the lining of the uterus)
- Li-Fraumeni syndrome (TP53 gene) related to breast cancer, soft tissue sarcoma, bone cancer, leukemia, brain tumors and adrenal cancers
- Retinoblastoma (gene: RB1) linked to eye cancer, cancer of the pineal gland, bone cancer, melanoma and soft tissue sarcoma
- Werner syndrome (MEN1) related to pancreatic endocrine tumors
- Von Hippel-Lindau syndrome (gene: VHL) linked to kidney cancer
A FOCUS ON PREVENTING PANCREATIC AND GI CANCERS
Genetic testing doesn’t just help people who are at high risk for breast and ovarian cancer. The progress in genetic testing has been significant enough that experts at the John Wayne Cancer Institute hope to launch a program next year aimed at testing for pancreatic and hereditary colorectal cancers.
The program is being developed by Ora Gordon, MD, professor of genetics at the John Wayne Cancer Institute and director of medical genetics and integrative medicine at the Roy and Patricia Disney Cancer Center in the Providence Medical Institute in Burbank, and Anton J. Bilchik, MD, PhD, chief of medicine and chief of the John Wayne Cancer Institute’s gastrointestinal research program. A multidisciplinary prevention program for individuals at high risk for these diseases could save lives, Dr. Gordon says.
“Pancreatic cancer remains a cancer that is often very late-stage when detected, but early-stage pancreatic cancer is curable, just like early-stage breast cancer,” she says. “We want to identify people who may be at risk in advance of any symptoms and try to optimize prevention.”
A significant proportion of pancreatic cancer cases are hereditary, and genetic testing can assess for 13 gene mutations linked to the disease. Individuals deemed at high risk could undergo tests such as endoscopic ultrasound or upper GI exams to monitor the health of the pancreas. Not smoking and adopting a healthy diet might also minimize risk.
Testing for people at higher risk for colorectal cancer aims at detecting the gene mutations that cause Lynch syndrome and other forms of hereditary colon cancer. Lynch syndrome is the most common cause of hereditary colon cancer and puts individuals at risk for colon cancer, gynecological cancers and pancreatic cancer. People with Lynch syndrome should undergo colonoscopy more frequently. Doctors might also recommend aspirin therapy and lifestyle modifications to lower the risk of tumors, Dr. Gordon says.
The Institute and Saint John’s Health Center are ideal places to offer sophisticated genetic testing because of the availability of specialized imaging technologies, top-rated surgeons and cancer clinical trials available to patients with challenging types of cancer.
“I think what we’re coming to understand is that 15% to 20% of all common cancers have a significant hereditary component, and that has changed the way we evaluate people,” Dr. Gordon adds. “Family history is important, but there are people who don’t know their history. Finding new tools to evaluate these people is really going to change the game.”