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The High-Risk Cancer Genetics Program at �ٺ���Ƶ Health’s Perlmutter Cancer Center is reshaping strategies for genetic risk assessment for cancer to better identify those who might benefit from testing. With enhanced methods to capture high-risk patients, experts hope to be able to intervene earlier to prevent the disease or detect it at an earlier, more curable stage.

Reimagining Genetic Screening Methods

Innovations from the program, such as a novel delivery model for genetic screening, have fostered enhanced collaboration to increase patient access to genetic services. The delivery model was developed with collaborators at the Huntsman Cancer Institute and adapted for �ٺ���Ƶ by Devin Mann, MD, associate professor in the Departments of and , and teams at the and Digital DesignLab.

As the landscape of cancer genomics and clinical genetics evolves rapidly, thanks to advancements in basic and translational research, the program team has implemented continuous quality improvement initiatives to keep pace with the frequently changing guidelines developed by the National Comprehensive Cancer Network (NCCN). Recently, this new virtual health model proved its mettle as new prostate cancer testing guidelines were implemented by the NCCN. The updated guidelines stipulate that any man with advanced prostate cancer automatically qualifies for genetic testing.

“We knew in advance that the NCCN planned to revisit the guidelines,” notes program director Ophira M. Ginsburg, MD, associate professor of medicine and population health. “With our advanced use of technology and innovative service models, we were able to rapidly mobilize to offer testing for this population.”

Dr. Ginsburg’s team of genetic counselors collaborated with David R. Wise, MD, PhD, assistant professor in the Departments of Medicine and , to develop screening materials aligned with the new standard. The genetics team extended the Group Counseling Webinar model, originally used only for those at higher risk for hereditary breast and ovarian cancers, to include men meeting the new prostate cancer testing criteria. This new application is expected to go live in early 2020, and the team will continue to collaborate with other �ٺ���Ƶ faculty to develop additional applications for other commonly inherited diseases.

Broadening Risk Identification’s Reach

The program’s focus on the rapid development of innovative strategies to bring screening to more patients is a response to the underutilization of screening services by patients who meet the criteria, notes Dr. Ginsburg. “At least 50 percent of people who would qualify for genetic testing under current guidelines are not identified as potentially high risk or are not offered genetic testing—despite declining costs and increasing insurance coverage for such services,” she says.

To increase the utilization of genetic screening services, the High-Risk Cancer Genetics Program team stays up to date with rapidly evolving research and guidelines, leads educational initiatives for �ٺ���Ƶ faculty and students, and trains the next generation of clinical providers, including genetic counseling students. Cancer genetic counselors actively participate in tumor boards, providing genetics expertise that is an increasingly vital part of cancer care.

For example, when a multigene panel identifies a potential gene variant that may signal a risk of developing pancreatic cancer, genetic counselors will refer patients to the Pancreatic Cancer Early Detection and Prevention Center at Perlmutter Cancer Center’s Pancreatic Cancer Center, directed by Diane M. Simeone, MD, the Laura and Isaac Perlmutter Professor of Surgery in the . The relationship, Dr. Ginsburg says, is bilateral.

“If Dr. Simeone’s team identifies a high-risk family with a BRCA2 mutation, they will deal with the pancreatic cancer–related clinical management,” she says. “Then they refer that individual or the family members who need counseling for other implications of BRCA2. It’s a seamless operation.”

“Cancer Moonshot” Grant Takes Aim at Screening Barriers

Identifying individuals who have inherited cancer susceptibility can be critical for tailoring cancer prevention, screening, and treatment strategies, adds Dr. Ginsburg. “Genetic testing efforts focused mainly on cancer patients can miss individuals at high risk who don’t have a close relative currently undergoing cancer treatment,” she says. “This is a really big gap. We’re missing most of the people out there who really can benefit from cancer genetic services.”

Dr. Ginsburg is co-principal investigator of a 2018-launched “cancer moonshot” study funded by the National Cancer Institute through a 5-year $5 million grant. Working with the Huntsman Cancer Institute at the University of Utah, the High-Risk Cancer Genetics Program will use a clinical decision support tool embedded within electronic medical records to automatically identify cancer-free patients in the primary care setting who qualify for genetic testing.

The BRIDGE (Broadening the Reach, Impact, and Delivery of Genetic Services) study will randomize patients from 48 clinics in Salt Lake City and New York City to 2 genetic counseling strategies: enhanced standard-of-care and an interactive web-based counseling platform via a chatbot. Participants will answer follow-up questionnaires 4 weeks after test results and 12 months later to evaluate patient experience, their understanding and retention of the genetic and cancer risk information that they received, and their adherence to screening recommendations.

The study has the capacity to identify factors that influence whether people identified via clinical decision support algorithms follow through with testing. The researchers also plan to compare the rural and urban communities around Salt Lake City with the �ٺ���Ƶ catchment area, which includes a much more diverse population. The team is also preparing to pilot this service for individuals from ethnocultural minority groups, including Latin and Spanish-speaking patients.

“We’re only seeing the tip of the iceberg of the high-risk population in and beyond New York—even where multiple centers offer reasonable access to cancer genetics services,” says Dr. Ginsburg. ”The primary objective of this project is to increase the currently suboptimal level of referrals from busy practices by offloading that task from primary care providers to a semi-automated program.”

Making Sense of Genetic Markers

At the other end of the diagnostic spectrum, the increasing proliferation of direct-to-consumer genetic tests can mislead patients with incomplete disease risk information that lacks the in-depth genetic analysis needed to fully understand cancer risk. “Buyer beware: you could end up with a false sense of reassurance,” Dr. Ginsburg warns.

In prostate cancer, for example, the most common inherited mutation that increases risk is BRCA2, but a panel that screens for up to 12 target genes is available for men with locally advanced or metastatic prostate cancer, regardless of ethnicity, family history, or age of diagnosis.

“There are often discordant results even between CLIA-certified, New York State–approved labs,” Dr. Ginsburg says. “It’s not their fault, it’s just complicated, as there is a lot of new information coming at us because of the advent of multigene panels.” For example, with increasing numbers of results that include more than one variant of uncertain significance (VUS), often such VUSs are reclassified, usually from VUS to benign—but occasionally a variant is upgraded to pathogenic. “Fortunately, the labs we use notify ordering physicians of all reclassifications,” adds Dr. Ginsburg. “Our team follows up with our patients to ensure that they and their providers have the most up-to-date revised results and understand their meaning.”

To ensure that patients subsequently receive the best care based on test results, the program team reviews the most complex cases during a weekly clinical cancer genetics case conference. The expertise of clinical geneticist John G. Pappas, MD, associate professor in the , has proven crucial in interpreting more complex test results, and in navigating family histories that suggest a syndrome that might include non-cancer issues, Dr. Ginsburg adds.