Published Online: January 29, 2014
Ellen T. Matloff, MS
She has sounded the alarm on behalf of patients and families for whom a genetic mutation may be a warning sign for cancer. Matloff was a plaintiff in the case against Myriad Genetics, which prompted the US Supreme Court to end the monopoly in genetic testing. But as she has warned, this presents challenges for providers in managing patient expectations. Matloff addressed attendees at Patient-Centered Oncology Care 2013 at an evening reception November 14, 2013.
In the small world of genetic counselors, time is now divided into Before Angelina Jolie and After Angelina Jolie.
The roughly 3000 professionals in the United States who are certified to handle the complex task of ordering genetic tests and interpreting results have experienced both the good and ill effects of a sea change in their field, thanks to a number of factors, according to Ellen T. Matloff, MS, who has been a genetic counselor at Yale University since 1995.
The announcement on May 14, 2013, by one of the world’s most beautiful women that she had undergone prophylactic breast removal because of a faulty BRCA1 gene stunned the public and the medical community alike. Jolie’s announcement, which appeared on the op-ed page of The New York Times,1 set off a tidal wave of interest and inquiries about BRCA testing; calls to Matloff’s clinic and others soared.2
Then came the June 2013 US Supreme Court ruling that said genes could not be owned, which opened the door to competition in genetic testing for the BRCA1 and BRCA2 mutations, among scores of others. But as awareness and access have skyrocketed, so have opportunities for profit. And, as she has done repeatedly in the months since, Matloff sounded the alarm to the attendees at Patient- Centered Oncology Care 2013 on behalf of patients who, swayed by aggressive marketing, might order the wrong test or have results misinterpreted, resulting in poor medical decisions.
Harnessing the power of genetic testing to help cancer patients and families requires understanding what the tests can and cannot do, and patients are best served if their results are interpreted by a certified counselor, she said. Despite what might be believed, or portrayed in the media, most physicians have limited genetics training—a point doctors have admitted in surveys.
A positive test for a mutation does not guarantee a person will get cancer, nor does a negative result mean a person has no risk of cancer, Matloff warns. She pointed out in her presentation that only 10% of cancers are hereditary, which means 90% result from something else.
It’s important to understand risk factors, such as early onset of cancer, whether multiple family members are affected, and whether there are “related” cancers in the family. Factors such as unusual presentation of the disease and ethnicity can play a role in whether one person’s cancer means the rest of the family is at risk, she said.
Matloff’s arrival at Yale coincided with the cloning of BRCA1 (1994) and BRCA2 (1995). BRCA1 is associated with increased risk of breast, ovarian, and prostate cancer; BRCA2 carries risks of breast, ovarian, prostate, pancreatic, and male breast cancer. Jolie’s decision was driven by the presence of BRCA1, which her doctors said increased her risk of breast cancer 87%.1 Her mother died at 56, and other women in the family had died early.
The risks are real: data that Matloff presented show that compared with an overall risk of 11 to 13% of breast cancer in the general population, BRCA1 mutations are associated with a 55 to 58% increased risk; BRCA2 risks are 50 to 80%. Ovarian cancer risk rises from 1 to 2% of the population generally to 15 to 60% with BRCA1 and 15 to 40% with BRCA2.
Jolie was the first to state that while surgery made sense for her, it was not for everyone.1 But as Matloff reports, unfortunately, that message has not gotten through to some women, who have surgery based on “mutations of unknown significance,” or who demand BRCA testing when, in fact, a better review of the family history would have resulted in testing for a different mutation.
Matloff’s tale of an episode in a synagogue in her area highlights the concern: certain BRCA mutations are associated with increased rates of cancer among the Ashkenazi Jewish population, but these are very specific mutations. The local rabbi said that the congregation had been offered 100 free genetic tests and they could be handed out during the high holidays— and if “anything came up” the patients could follow up. Matloff was alarmed that testing would be done without the involvement of genetic counselors. Yet she knows that the rise of directto- consumer testing companies such as 23andMe makes these episodes increasingly common.
She walked the attendees through a series of examples to show just how complex the testing process can be, and how knowledge of family history prior to testing is essential. To begin with, it’s important to order the right test—yet Matloff has seen cases in which patients pay for tests that won’t even give them the answer they need.
Of note, within 2 weeks of Matloff’s presentation, the US Food and Drug Administration ordered 23andMe3 to halt marketing until it complied with the agency’s regulatory requirements. EBO
1. Jolie A. My medical choice. The New York Times. May 14, 2013. http://www.nytimes.com/2013/05/14/opinion/my-medicalchoice.html. Accessed January 7, 2014.
2. Beagin N. Genetic testing should come with counseling: American Cancer Society CMO, Supreme Court plaintiff among experts who warn of consumer risks. Am J Manag Care. 2013;19(SP13):SP441-SP452.
3.Caffrey MK. FDA tells direct-to-consumer genetic testing company to halt marketing. Am J Manag Care. 2013;19(SP13):SP453-SP454.