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MAGENTA Study Aims to Find Best Genetic Counseling Method for Online Cancer Risk Testing

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This article has been corrected to note that SU2C is funding the genetic testing for participants in the study. Color is performing the testing but is not providing any funding.

NEW YORK (GenomeWeb) – Recognizing that more people are seeking out genetic testing online to learn their cancer risks, researchers are conducting a large randomized study to identify best practices for scaling genetic counseling.

"If we want to make genetic testing available widely and move toward population testing, then we want to create the most efficient testing system possible," said Elizabeth Swisher, co-leader of the Stand Up to Cancer (SU2C)-Ovarian Cancer Research Fund Alliance-National Ovarian Cancer Coalition Dream Team, which designed and funded the 3,000-participant trial, called Make Genetic Testing Accessible (MAGENTA). Karen Lu from MD Anderson Cancer Center is the principal investigator.

"We have this paradigm where the patient has to come in and get pretest counseling, do the testing, and then get post-test counseling," said Swisher, who is also a professor of obstetrics and gynecology at the University of Washington. "But this isn't really based on data about how much counseling someone needs to optimize his or her experience and the outcomes from genetic testing."

Additionally, she cited a study that found nearly two-thirds of women whose doctors ordered testing for mutations in BRCA1 and BRCA2 genes associated with increased risk for breast and ovarian cancer received no genetic counseling at all, which Swisher said means that "people aren't following this model in reality."

Moreover, this traditional model may not scale quickly enough to match the growth in the genetic testing industry. A number of experts, including breast cancer pioneer Mary-Claire King, have been advocating for screening all women starting age 30 for deleterious mutations in BRCA1 and BRCA2, so those with pathogenic mutations can take preventive measures.

Inspired by King's call, a number of genetic testing companies in recent years have begun offering tests for BRCA1/2 and other cancer risk genes for a few hundred dollars. These companies also employ a consumer-facing online model that makes it easier for people to access testing even if they can't see a doctor or genetic counselor face to face.

Genetic testing firm Color operates such a model, and is also perfroming testing for MAGENTA study participants (funded by SU2C). In its commercial business, the company tests for 30 genes associated with hereditary cancer risk for $250, and charges $99 to only analyze BRCA1 and BRCA2 genes.

Color has been vocal about its goal to create a testing paradigm that supports population screening for BRCA1/2 mutations implicated hereditary breast and ovarian cancer syndrome, and mutations in genes known to cause Lynch syndrome and familial hypercholesterolemia. The Centers for Disease Control and Prevention has recognized that these conditions are underdiagnosed by the healthcare system, leaving many affected people and their families unaware that they're at risk.

However, insurers have fairly stringent coverage policies. For BRCA1/2, for example, insurers tend to only pay for testing when individuals have a family and personal history of breast and ovarian cancer, even though there is now ample data showing that using these parameters, the healthcare system is missing a substantial portion of the at-risk population.

In the face of insurance barriers, low-cost online testing services like Color's are enabling more people to get tested. Color is even partnering with self-insured employers that are making these tests available to their employees through benefits programs.

However, if population screening is the goal, resulting in many more women being tested than are presently, then there will need to be greater capacity for genetic counseling as well. This was on Color's mind when it launched its service in 2015.

"There aren't enough genetic counselors in training or ready in practice to actually be able to handle the volume of testing that would happen if you opened up universal access," said Alicia Zhou, head of research at Color. "In this paradigm, where you have more people coming in [for genetic testing], how can you make the existing genetic counseling resources more effective?"

Color worked with King, who is an unpaid advisor to the company, and the genetic counseling group at the University of California, San Francisco, to come up with a strategy. With input from genetic counselors from UCSF and around the country, Color developed an educational video to address questions that patients generally have before they get tested.  

In the post-test setting, Color's service includes genetic counseling for the price of testing. When individuals have positive results, indicating a pathogenic mutation was found, Color requires that they view their results with a counselor on the phone who can help them understand the report. "These are the people that have a life-changing result," Zhou said. "They really need to think about how this [result] affects them and their families, and how they should change their own medical management based on the result."

According to Color, nearly 100 percent of people with positive results receive genetic counseling, though a few customers don't get their reports at all for reasons that are unclear. A subset of customers' physicians also waive genetic counseling through Color and they get their results through their doctors. The number of customers with negative reports who get genetic counseling is significantly lower, because counseling is voluntary for them, according to the firm.

MAGENTA will essentially compare the effectiveness of the type of strategy Color is employing against the traditional paradigm, where all patients speak with a genetic counselor before and after testing. Swisher emphasized, however, that Color did not have input into the design of the trial but helped design the online interface for the study.

In order to partake in MAGENTA, women must speak English, be at least 30 years old, reside in the US, have at least one ovary, and have a personal or family history of breast cancer, or a family history of ovarian cancer. Those who have had ovarian cancer previously, or have gotten genetic testing or counseling for cancer risk before are ineligible. Participants must be willing to be genetically tested, share their results with a healthcare provider, and answer questions for up to two years.

Qualifying participants first create an online account with Color, enter their family history, and receive pretest genetic counseling based on their random enrollment in one of four arms. In arm A and B, participants watch Color's pre-test educational video. In arm C and D, participants watch the video and speak to a genetic counselor on the phone.

Upon receiving the spit kit in the mail, participants will provide a sample for sequencing, and they are informed via email that their results are ready. At that point, those in arms A and D with positive reports speak to a genetic counselor over the phone to learn about them, while those with negative results can view them in their Color account online. In arms B and C, participants with positive or negative reports speak to a counselor to learn their results. Subsequently, participants will be asked to answer emailed survey questions about their experience with genetic counseling after three months, a year, and at two years.

Through these follow-up questionnaires, the MAGENTA investigators hope to gain insights into a number of key questions. For example, to what extent does someone with a negative report, who views the educational pre-test video but skips genetic counseling, understand her results and cancer risk? "What about the patient who has a negative genetic test result but has a strong family history?" posited Swisher. "Does the negative test result give them a false sense of assurance that they're at normal risk?"

MAGENTA study participants will receive the same reports that Color's commercial customers receive. "The report tells you more than just if you have a mutation," Zhou said. "What's really important for people to understand is that [a negative test report] is not a clean bill of health for them to never think about their cancer risk ever again."

Color's report emphasizes that women at average risk of cancer should still follow screening recommendations from professional societies, and discusses the residual risk that an individual may still have, due to environmental factors for example, even if genetic testing didn't detect a mutation.

The company also makes a significant effort to collect information from its customers about other family members with cancer. This allows Color to run clinical algorithms and assess if an individual is still at increased cancer risk based on their family history despite a negative genetic test result. Individuals who are at increased risk of cancer based on their family history still receive an elevated risk report that states they need to be screened more frequently than the average risk patient.

The findings from MAGENTA could, on the one hand, validate the approach Color has taken toward communicating risk through a pre-test video, by requiring genetic counseling for those with positive results, and through its reports. On the other hand, the study could also identify scenarios where patients want or need more support understanding their results, but aren't getting it.

"If the data from the MAGENTA study reveal that there is a hole in the current delivery model, then we would absolutely change our delivery model to address those," Zhou said. "Part of the reason we're actively participating in MAGENTA is because we want to know what is the best delivery model and that has to be done in a data-driven way."

So far, there has a been a lot of interest in participating in MAGENTA. In fact, a local Minnesota news report inspired so many to sign up for the study that the demand outstripped Color’s genetic counseling capacity. The researchers reached out to local genetic counselors in Minnesota for help, and Zhou said that many of them eagerly agreed to counsel the overflow of patients, and this maintained the enrollment schedule.

Swisher expects MAGENTA to be fully enrolled in the next three to four months.