By Cheryl Platzman Weinstock
Since the human genome was fully sequenced a decade ago, research in the field of genetics has advanced at breakneck speed. Today tests are available to find a genetic link for more than 2,500 diseases (10 years ago, that number was around 900). Doctors, in turn, have eagerly embraced the emerging technology; with a blood test they can help patients determine their risks for potentially treatable and preventable conditions, including many types of cancer. The only problem: Many doctors have little to no formal training in genetics, and that lack can lead to devastating mistakes.
A recent report from ARUP Laboratories, a national pathology lab affiliated with the University of Utah, found that over an 11-month period in 2010, clinicians ordered the wrong genetic test nearly a third of the time. A 2012 study in The Cancer Journal reviewed dozens of cases in which doctors without specialized training made similar mistakes: ordering wrong or unneeded genetic tests, misinterpreting the results of correct tests, or failing to refer a patient to a genetic counselor even when there were key red flags, like a strong family history for a disease. In one case, a doctor's misunderstanding of a test resulted in a 41-year-old woman's having an unnecessary hysterectomy.
For Lupe Acosta, 47, a misinterpreted genetic test for breast cancer led her to have a second mastectomy she likely didn't need. In 2011 Acosta, a mother from a small college town on the outskirts of Los Angeles, had her blood tested for mutations in the two genes (BRCA1 and BRCA2) linked to hereditary breast and ovarian cancer. She'd already undergone a mastectomy to remove her left breast after being diagnosed with cancer of the milk ducts earlier that year; given that her mother had breast cancer, her oncologist wanted to see if the disease was inherited.
"When I found out the test results were positive, I panicked," says Acosta. For a second opinion, she turned to doctors at City of Hope Comprehensive Cancer Center in Duarte, California; it was there that she was connected with oncologist and geneticist Jeffrey Weitzel, MD, chief of the center's division of clinical cancer genetics.
"Lupe's results simply stated that she had a variant of uncertain significance,'" says Weitzel. "Her genes did show some irregularities, but the test couldn't say for sure if they were harmful. More genetic testing and counseling should have been done before treatment options were offered." Weitzel himself went on to order a second, more complete type of breast cancer test (called BART) to further rule out any possible cancer-causing mutations. When no mutations were found, Weitzel advised Acosta that her risk did not warrant a preventive mastectomy.
But where Acosta's peace of mind was concerned, it was too late. "After being told I had a mutation, I couldn't shake the feeling that I was a ticking time bomb," she says. "I had to go ahead with the surgery if I was ever going to move on with my life."
In Weitzel's view, Acosta's ordeal highlights why it's so important that clinicians be adequately schooled in genetics before they offer testing to patients. It's hard to disagree -- especially when many of the very doctors who counsel patients confess to being clueless. In a recent study funded by the National Human Genome Research Institute, 74 percent of more than 200 internists said their knowledge of genetics was "very to somewhat poor," yet 41 percent of them admitted to going ahead and ordering tests. In contrast, board-certified genetic counselors spend at least two years in graduate school studying the human genome and how our DNA can affect our health. They're highly trained to evaluate test results and can help you navigate risk reduction and treatment options.
Karla Wheeler, 32, says getting the wrong result when she was tested for Lynch syndrome -- a disorder that can cause cancer in the small intestine, ovaries, and particularly the colon -- caused months of anxiety during which she believed she'd have to give up her dream of having children. Several generations of Wheeler's family (including her father) had been plagued with colon cancer. "If I had the gene, my husband and I didn't want to pass it on to our kids," says Wheeler. She shared her concerns with her internist, who referred her to a gastroenterologist.
"The gastroenterologist said there was a new test that could determine if I had the gene, and I could have my blood drawn right in the office," says Wheeler. "When I called for the results, the receptionist told me I'd tested positive for the mutation." Concerned, Wheeler took her results to a new doctor, who recommended she go over the test with a genetic counselor. That's when Wheeler found Jeanne Homer, a certified genetic counselor at Hoag Family Cancer Institute in Newport Beach, California -- and her future changed again.
After studying Wheeler's report, Homer said it was unlikely that she was carrying the mutation after all. Since her father had been diagnosed with colon cancer, Homer said he needed to be tested first. "Testing him allowed us to locate the specific genetic mutation on one of four genes linked to Lynch syndrome. This was the only way to confirm that the cancer was hereditary." Luckily for Wheeler, she hadn't inherited the mutation.
The obvious solution to preventing stories like Wheeler's is more and better training for doctors -- but so far, no medical groups have come up with a large-scale plan. However, in 2010, Life Technologies, a global biotech company, gave generous funding to geneticist and cardiologist Eric Topol, MD, director of the Scripps Translational Science Institute in La Jolla, California, to create the College of Genomic Medicine, an online teaching tool. Expected to launch later this year, the site will educate doctors about genetic testing and offer certification to those who complete a three-part course and final exam. Medical schools are also taking notice: Last year the Icahn School of Medicine at Mount Sinai in New York began offering a course in which all students have an opportunity to sequence, analyze, and interpret their genome. "Our hope is that the class will help them understand how to use and interpret new technologies in genetics even if that's not their specialty," says Eric Schadt, PhD, chairman of the school's department of genetics and genomic sciences.
Until the majority of doctors catch up with the science, meeting with a genetic counselor or a clinician with training in the field is your safest option. Colleen Carroll, 46, has been on a mission to get everyone in her family to a counselor since she found out she was tested for the wrong gene. After being diagnosed with ovarian cancer in 2002, Carroll got tested for the BRCA1 and BRCA2 mutations at her oncologist's urging. When the results came back negative, Carroll thought she was in the clear.
A few years later, however, cancer started striking members of her family, including a second cousin who died from ovarian and endometrial cancers. When that cousin's father was diagnosed with intestinal cancer, the family finally met with a genetic counselor, who found that they, like the Wheelers, carried a mutation for Lynch syndrome. "Colleen did have a genetic mutation -- it was just on a different gene that couldn't be picked up by BRCA testing," says certified genetic counselor Ellen Matloff, director of cancer genetic counseling at the Yale Cancer Center.
Today, even as she keeps up with regular colonoscopies, Carroll wonders if she could have spared her family if she'd seen a genetic counselor earlier. "My oncologist saved my life, and I'm forever grateful for that," she says. "But if I had been given the correct gene test first, maybe I could have saved my cousin."
Cheryl Platzman Weinstock is a science writer who specializes in women's health issues.