Debbie McCarron was prepared to get both of her breasts taken off if a blood test in December 2006 revealed she carried a gene that vastly increases the risk of breast cancer. Having survived the disease five years earlier, she didn’t want to risk getting it again.
To her relief, her oncologist told her the test, done by Myriad Genetics Inc., had come back negative, “just like I knew it would,” McCarron recalls her doctor saying.
He was wrong. The results, in fact, were positive. McCarron didn’t learn this, though, until July 2009, more than two years later, when a genetic counselor reviewed the test following McCarron’s surgery to remove a new malignant breast tumor. Since then, her oncologist, Haresh Jhangiani, told Bloomberg he isn’t clear about what happened.
“I don’t think she was positive. Was she positive?” the doctor said. “I would not tell her it was negative if the test was positive, there must be something more to it.”
McCarron, now 50, was devastated when she found out. “The whole world crumbled down on me that day,” the Huntington Beach, California, woman said in an interview. “I never would have gotten that second cancer.”
More than 2,700 diseases can now be identified through gene testing, compared with fewer than 800 in 2000, according to the government-funded website GeneTests. DNA screening offers the potential to transform medicine by predicting the risk of cancer or other severe diseases years in advance. Yet the very nature of the tests creates the potential for catastrophic error because they’re often used to make irreversible decisions, such as terminating a pregnancy or undergoing surgery to prevent cancer.
The tests can cost thousands of dollars, so doctors and patients often delay using them fearful insurers won’t pay. They’re complex in their makeup and difficult to corroborate. And there is a general lack of training among doctors who authorize them and must explain the results, according to recent studies.
As a result, errors such as the one affecting McCarron can go undetected for years, harming entire families. Since she found out she was positive, McCarron has advocated her family get tested, helping them navigate a system that has thrown up multiple barriers along the way. So far, 10 relatives have tested positive, including McCarron’s father, uncle, aunt, six cousins and her oldest daughter.
ARUP Laboratories, a nonprofit laboratory affiliated with the University of Utah, found that 30 percent of orders for complex gene tests from February to December 2010 contained mistakes in handling by clinicians. Doctors requested the wrong test or mixed up rare diseases with similar names, or ordered a test for one cancer mutation when another ran in the family, said Christine Miller, an ARUP genetic counselor.
About 74 percent of internists said their knowledge of genetics was somewhat or very poor and 79 percent wanted more training on when to order the tests, according to a Columbia University study surveying 220 internists.
“Even if you have been out of medical school for five years, you are totally out of date,” said Wendy Chung, a pediatrician and geneticist at Columbia University Medical Center who was a co-author on the study.
Since McCarron found out about her bad gene in 2009, she has urged relatives at family reunions to get tests. She has also intervened multiple times when her relatives’ doctors have had trouble ordering the right test or explaining the results, according to McCarron.
With one cousin, the testing lab called McCarron on her mobile phone to ask which test to run; the doctor hadn’t completely filled out the order, she said. Another cousin’s doctor ordered the wrong test, while other doctors weren’t familiar with recommended screenings for those who test positive, she said.
When it comes to genetic tests, too many doctors “don’t know what to test for, they don’t know what box to check, they don’t know how to read the results, they don’t know what to tell their patients,” McCarron said.
“My family’s experience has been horrible,” she said. “It is important to me that this not happen to anybody else.”
Other families have faced similar issues, according to genetic counselors at the Yale Cancer Center and elsewhere who have published two studies with details on 30 cases in which doctors have misordered, misread, or misinterpreted gene tests. One study was published in the July/August 2012 edition of the The Cancer Journal, while the other was released in August 2010 in the journal Connecticut Medicine.
The situation may get worse as doctors move from testing one gene at a time to dozens or thousands -- increasing the odds of ambiguous results that are easy to misinterpret.
“If we can’t even interpret relatively simple genetic tests for one or two genes, how are these people going to interpret a complex panel that includes tens or thousands of genes that are rare and we know little about?,” said Ellen Matloff, director of cancer genetic counseling at the Yale Cancer Center in New Haven, Connecticut, and a senior author on the two studies.
McCarron is 5 feet 2 inches tall with shoulder-length dark brown hair, and likes to hug people. Raised in the Los Angeles area, she and her husband have two daughters.
She was first diagnosed with cancer in December 2001, when she was 39. She got a mammogram after finding a lump in her right breast. While that one was benign, her mammogram found a real tumor on the left side. She was treated with surgery, chemotherapy and radiation to make sure it didn’t return.
It wasn’t the first case of early cancer in her family. McCarron’s paternal grandmother died at 35 from ovarian cancer, and an aunt contracted ovarian cancer at 48.
McCarron said that while she mentioned the ovarian cancers to her doctors, she didn’t press the matter initially because she didn’t have any idea that her relatives’ diseases might be related to her breast cancer.
McCarron’s mother wanted to be sure there was no genetic link. She pushed Debbie to get tested for the BRCA1 and BRCA2 breast cancer genes in 2002. The BRCA test, sold by Salt Lake City-based Myriad, looks for mutations in the two genes that are the most common forms of hereditary breast and ovarian cancer.
Jhangiani, McCarron’s oncologist at the time, initially said he wasn’t sure the test was necessary, McCarron and her mother, Elizabeth Fabrizio, recalled in interviews.
“He kept telling me this is a very expensive test that your insurance isn’t going to pay for,” McCarron said.
While she was initially turned down by her insurer, she said an appeal won her at least a partial payment for the test, which Myriad now sells for $3,340. She gave blood on Dec. 14, 2006, and Myriad sent a first set of results to Jhangiani on Dec. 27.
Not too long afterward, she said, -- McCarron doesn’t remember the date -- Jhangiani told her the test was negative, that she didn’t have a cancer-causing mutation.
“I was ecstatic,” McCarron said. “It was a huge monkey off my shoulder.”
Relieved, she moved on with her life. She was now so confident, she said, that she put off a mammogram for five months. When she finally got the X-ray on Jan. 6, 2009, it found the right-breast lump.
This malignancy was aggressive and had already spread to five lymph nodes. “I thought this was it,” McCarron recalled.
Jhangiani was incredulous when McCarron told him she had breast cancer again, according to her husband, Joseph Alexander McCarron, and her mother, both of whom were present at the appointment. McCarron wanted both breasts removed. Jhangiani recommended a less radical operation that would only take out a lump of tissue around the new tumor.
That day, McCarron decided she needed a new doctor. “No more Dr. J.,” reads her calendar for Jan. 13, 2009.
McCarron then had both breasts removed, along with her uterus and ovaries, in a six-hour operation. That was followed by three months of “dose dense” chemotherapy, an intense form of treatment where doctors reduce the time between treatments to maximize the odds of a cure.
One drug in her cocktail, Adriamycin, is nicknamed the “red devil” for its bright color and nausea-inducing effects.
McCarron lost her hair and was constantly fatigued, dizzy or nauseous from her treatments. Sometimes, after going to the bathroom, she would lay on the cold bathroom tile for as long as an hour, too weak to move, she said. Twice she needed blood transfusions.
In the summer of 2009, McCarron’s new oncologist, Khosrow Mahdavi, recommended she visit a cancer genetic counselor at the hospital. Her new doctor insisted that she go even when she protested that she had been tested for the breast cancer genes and was found not to have them, McCarron said. Mahdavi confirmed the account in a telephone interview.
In the early afternoon of July 10, 2009, Mariana Niell, a genetic counselor, met McCarron and her mother on the second floor of the cancer center at Hoag Hospital Newport Beach. She took a detailed family history, noting the relatives who had died from ovarian cancer.
Based on the family and personal history alone, Niell estimated that McCarron had as much as a 94.9 percent chance of having a BRCA mutation, according to a report she sent to Mahdavi. When McCarron told Niell she had tested negative for the genes, the counselor contacted Myriad to get the results. When the lab couldn’t immediately locate the records, McCarron and her mother returned to her new doctor’s office and the clerk there called Jhangiani’s office to get his copy of the results.
“I remember standing there while they called and asked if they could please fax over the BRCA test, and this is what they sent over,” Fabrizio said.
The single-page fax, stamped 2:22 p.m. on July 10, 2009, contained a sentence in bold type: “No large rearrangement detected.” In four places it said, “No mutation detected.” Large rearrangement is a type of mutation that accounts for 6 percent to 9 percent of mutations in the BRCA1 and BRCA2 genes, according to Myriad.
At 8:27 a.m. the next business day, Myriad faxed along its own copy of the findings. Unlike the version received from the doctor’s office, this one was three-pages long and contained additional results.
Here is where the confusion may have started. Unbeknownst to McCarron, Myriad had performed not one but two tests on her blood. One test, designed to find defects called large rearrangements, was negative. The other, Myriad’s main test for defects in the BRCA1 and BRCA2 genes, concluded she was “positive for a deleterious mutation.”
The mutation gives McCarron as much as an 84 percent risk of breast cancer and a 27 percent chance of ovarian cancer by age 70, the report said. Myriad’s records, some of which the company provided last month to McCarron, indicate it was sent via Federal Express to Jhangiani’s office on Dec. 27, 2006.
The second test with negative results was sent to Jhangiani’s office more than a week later, on Jan. 9, 2007.
McCarron cried as she called her mother to share the news. “It was one of the worst days of my life,” said McCarron. “It was almost worse than hearing you had cancer.”
Jhangiani, McCarron’s initial oncologist, is listed as senior physician on the website for Compassionate Cancer Care Medical Group, a group practice that has offices in Fountain Valley, Corona, and Riverside, California. In a telephone interview, he said he remembered little about the chain of events surrounding McCarron’s test.
After looking at copies of McCarron’s test results e-mailed to him by Bloomberg News, Jhangiani said his initials were missing from the page with the positive finding.
“There is a very good possibility I never even saw the second page,” he said. “The fact that the second page does not have my signature and it is positive and it has not been circled means I never even saw that.”
If he had known about a positive result, he “definitely” would have advised McCarron differently, including about the possibility of having her breasts and ovaries removed to prevent cancer, he said.
Laboratories should report positive test results on one page, Jhangiani said, as his office has “tons of paper” coming in. “If any part of the test is positive they should report it on the first page,” he said. “They didn’t report it the way it should be reported.”
Jhangiani said he would need to go back to his records to determine what might have happened.
A week later, a call to Jhangiani was returned by his lawyer, Raymond McMahon of Bonne Bridges Mueller O’Keefe & Nichols in Santa Ana, California, who said in an e-mail he was “not comfortable under the situation before us to state anything further.”
Rebecca Chambers, a Myriad spokeswoman, defended the company’s presentation of its results. They “do not require physician interpretation,” she said in an e-mailed response to questions.
However, Myriad’s decision to conduct and report a second test “could confuse some people” unfamiliar with the procedures, according to Chung, the geneticist at Columbia University.
Someone at Myriad may have realized that the negative result, coming more than a week after the first positive finding, might need clarification. Myriad’s communications log for McCarron’s case lists an outbound telephone call to Jhangiani’s office on Jan. 16, 2007.
“Left voice mail for RN in office to clarify test results -- Explain the BART results and that they do not change the interpretation” of the main test, the communications log read. Following inquiries by Bloomberg, Myriad provided copies of the communications log to McCarron.
Myriad’s typical practice is to contact doctors after results are delivered if they order a new test, Chambers said. Jhangiani hadn’t previously ordered the large rearrangement test, she said.
“It is important to remember the test was done for free and in a good faith effort to provide the patient and physician with important information,” Chambers said.
Matloff at the Yale Cancer Center, who has studied why doctors make mistakes in ordering and interpreting cancer gene tests, criticized Myriad for marketing complex tests to gynecologists and other doctors who may not have expertise in genetics.
In an e-mail, Myriad said it markets its tests to gynecologists, oncologists and surgeons in accordance with various professional society guidelines regarding genetic testing.
“When companies start marketing their tests and making them available and say you are qualified to order the test when you probably aren’t, it lowers the standard of care,” said Sue Friedman, executive director of Facing Our Risk of Cancer Empowered, a nonprofit group in Tampa, Florida.
Harried primary-care doctors may not have the time to properly explain the results.
“It takes more than a 10-minute meeting with a patient” to explain cancer gene-test results, Friedman said.
Matloff, and Columbia’s Chung, are plaintiffs in a patent lawsuit against Myriad, and Friedman’s group filed a brief in support of the plaintiffs. A federal appeals court ruled Aug. 16 in favor of Myriad.
The number of doctors certified in genetics isn’t growing much, and is perhaps one-third of what is needed, said Michael Watson, executive director for the American College of Medical Genetics and Genomics. The lack of education about genetics “could become increasingly problematic” as more patients start asking primary-care physicians for such tests, he said.
After McCarron found out about the bad gene, there was a clear next step ahead. Her family needed to be informed, she said. Each child of someone with a BRCA1 or BRCA2 gene mutation has a 50 percent chance of inheriting it.
McCarron called her three half-sisters and her father, from whom she had inherited the cancer-risk gene, and arranged to meet them that night. She brought copies of her test results for each, and explained what it could mean about their risk of getting cancer and why testing was important. She repeated the performance two weeks later for her aunts and an uncle.
McCarron, who has resumed working in her job as a mortgage underwriter, now is busy with activities that raise money for breast cancer research and awareness.
In an interview at her home, McCarron wore a pink sundress, the color of breast cancer activism, pink nail polish, earrings, and two pink bracelets. Her closet is full of dozens of breast-cancer themed shirts, hats and jewelry.
One shirt reads, “Yes they are fake (My real ones tried to kill me).”
McCarron said she has mixed feelings toward her first oncologist, Jhangiani. She feels betrayed, even though “it obviously wasn’t done on purpose” she said.
While she has thought frequently about confronting the doctor, and even drafted several letters to him, she hasn’t mustered the courage to go through with it. She also thought about suing the doctor and talked to a lawyer, but said she has decided against it.
Now her fear is that her life may be shortened because she didn’t get the correct gene-test results in time to prevent another cancer, she said. There may be a few malignant cells left from the second breast cancer somewhere in her body, she says, and they may someday return.
“I definitely think my life is going to be shorter because of it,” she said. “I don’t want to be taken off this earth before my time.”