The decision about whether to get tested for a genetic mutation that may predispose a person to certain cancers is a difficult one for many patients to make. Even more difficult for mutation carriers is deciding whether to undergo a prophylactic surgical procedure.
How would cancer genetics specialists themselves make these tough choices? Have their perspectives changed over the years, with increased knowledge about genetic testing, surveillance, and treatment?
Ellen T. Matloff, MS, CGC, director of the Yale Cancer Genetic Counseling Program at the Yale School of Medicine/ Yale Cancer Center, in New Haven, Connecticut, is getting more interest than ever in these questions in light of the June 13, 2013, US Supreme Court decision involving Myriad Genetics, in which she was a plaintiff. Myriad had vigorously enforced patents to control a monopoly in genetic testing for mutations of the BRCA1 and BRCA2 genes, indicators of the likelihood of developing breast or ovarian cancer.
In light of the ruling, Matloff’s research on the willingness of genetic specialists to be tested for mutations, or even undergo surgery, seems even more timely. She discussed her results at the March 2013 annual meeting of the American College of Medical Genetics and Genomics in Phoenix, Arizona. She presented findings of a follow-up survey of 216 active members of the National Society of Genetic Counselors’Special Interest Group in Cancer.1 In late June, Matloff offered a presentation to members of the medical community in New York City, portions of which were broadcast nationally on FOX News.
“We originally conducted this study in 1998, when cancer genetic testing and counseling was in its infancy, and we had little or no data to tell us what would be the efficacy of prophylactic surgery, surveillance, or chemoprevention for carriers,” Matloff explained in Phoenix. The follow-up, Internet-based, anonymous survey was conducted in July 2012; male respondents were asked to answer questions as they would for a close female relative.
Much has changed in the 14 years since the 1998 survey—notably, the fact that now 58.3% of the specialists surveyed said that they would opt for bilateral prophylactic mastectomy if they tested positive for a deleterious BRCA mutation at age 35. When that question was asked in 1998, only approximately 25% said that they would choose to have their breasts removed if they were found to be BRCA mutation carriers. Decreased risk (57.9%) and avoidance of fear/worry (49.1%) were cited most often by respondents who said they would choose mastectomy if found to be mutation carriers. Twelve percent indicated that a lack of confidence in surveillance would be a factor in their decision to have their breasts removed.
“This was a very controversial issue in 1998, and it still is to some extent in 2012,” said Matloff. Those who would choose not to have the prophylactic procedure listed confidence in surveillance (33.3%), negative impact of surgery on body image and sexuality (22.2%), and the fact that the surgery would not provide 100% protection against recurrence (10.6%). On the question of whether to undergo BRCA testing if risk for the mutation was determined to be 50%, a large majority of respondents to both surveys said that they would choose to be tested: 84.5% of those responding to the 1998 survey and all but 2 of the respondents in 2012 (99.1%). Among the reasons 2012 respondents gave for choosing to be tested were that the information would aid in medical management, it would be helpful to their families, and it would lessen uncertainty; 55.6% of the affirmative respondents said they would choose to be tested for the 50% probability that they would test negative.
Matloff added that she did not present data on whether BRCA mutation carriers would have their ovaries removed, because the percentage was high in both surveys and not statistically significant. The researchers also found statistically significant differences in attitudes toward prophylactic surgery for Lynch syndrome between the 2 surveys. When asked if they would choose prophylactic colectomy if positive for a deleterious HNPCC mutation at age 35, only 16 respondents to the 2012 survey (7.4%) said they would, compared with 27 people (17.4%) who answered affirmatively in 1998.
Respondents in 2012 indicated confidence in colonoscopy, lowered quality of life and body image, and a willingness to postpone surgery until detection of a lesion or polyp as reasons for this choice. However, when the same question was asked with regard to removal of the uterus or ovaries due to an elevated Lynch syndrome risk, participants were more inclined to respond affirmatively.
Nearly 80% of 2012 respondents said they would have their uterus removed if found to carry the HNPCC mutation at age 35, compared with 54.1% in 1998. Similarly, nearly 78% of respondents in 2012 indicated that they would have their ovaries removed versus 52.4% in 1998. The survey also explored the issue of anonymity in genetic testing with respect to health insurance, and the results indicate that respondents are for the most part confident that billing their insurance company for testing would not be detrimental, with 94.9% of the 2012 respondents replying that they would, compared with just 23.9% in 1998. “I find this particularly interesting because I’m not sure we would even think to ask these questions in 2012, but these were top of mind in 1998,” Matloff observed.
Matloff explained that gauging the perspectives of experts on issues related to genetic testing and possible interventions is especially important, insofar as the specialists surveyed “arguably have the most education and clinical experience in cancer genetic counseling and testing.”
“We now know that genetic testing is well established, as compared with 1998, and that more clinicians know about BRCA and Lynch syndrome,” said Matloff. She added that more clinicians are treating patients who carry mutations, and they can see both the natural progression of disease and also the stress inherent for people who test positive, as well as the stress among unaffected carriers, as they undergo surveillance, chemoprevention, and prophylactic surgery.
Another factor that may affect genetic testing is cost, which Matloff expects will come down in light of the Myriad decision. Within the next few years, Matloff believes that the costs associated with testing will decline from $4000 for 2 genes to under $1000 to sequence the entire exome. This decrease in costs will bring genetic testing into the average marketplace with broad applications for reimbursement, Matloff believes.2 As more competitors enter the testing marketplace, choices and costs will improve for consumers, she explained.
1. Matloff E, Bonadies D, Brierley K, Moyer A. Changes in specialists’ perspectives on cancer genetic testing, prophylactic surgery and insurance discrimination: then and now. Presented at the Annual Clinical Genetics Meeting of the American College of Medical Genetics and Genomics; March 19-23, 2013; Phoenix, AZ; Abstract 27.