Online Tool IDs People With Genetic Mutations Linked to Cancer

Megan Brooks

August 30, 2022

A new online tool can quickly and accurately identify individuals who may benefit from genetic testing because they likely carry pathogenic germline variants (PGVs) in a diverse spectrum of cancer susceptibility genes.

The PREMMplus online tool was developed and validated by researchers at Dana-Farber Cancer Institute in Boston using three cohorts involving more than 30,000 individuals who had undergone multigene hereditary cancer risk testing.

The study was published online August 15 in the Journal of Clinical Oncology.

"Our findings show that PREMMplus has the potential to change the model by which patients and family members are referred for genetic testing and counseling," senior author Sapna Syngal, MD, MPH, with Dana-Farber and Brigham and Women's Hospital, said in an institution news release.

Traditionally, when there is concern about a family cancer history, the individual is referred to a genetics clinic, where a counselor takes a complete family history.

"At a time when there's a shortage of genetic counselors, PREMMplus can help streamline risk assessment and ensure that their time can be focused on where they're most needed ― helping people understand the results of genetic testing and the options available when a cancer-susceptibility gene is found," Syngal says.

Online Tool

The tool uses clinical data (age, sex, ethnicity, and personal/family history of 18 cancers) to determine an individual's likelihood of harboring a PGV in 19 cancer susceptibility genes.

A PREMMplus score of 2.5% or greater had a 89% – 94% sensitivity and >97% negative predictive value (NPV) for identifying individuals with PGVs in 11 well-defined, "category A" high-penetrance cancer risk genes: APC, BRCA1, BRCA2, CDH1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53.

These PGVs "represent diverse types of inherited cancer risk for which there are established risk-reduction guidelines," the study team says. Cancers associated with these PGVs include breast, ovarian, colorectal, pancreatic, and prostate cancer, as well as those that make up Lynch syndrome.

The ability of PREMMplus to identify individuals with PGVs in "moderate-penetrance" cancer risk genes (such as CHEK2 and ATM) was somewhat reduced but was still "quite strong" (84% – 90% sensitivity and >93% NPV), the study team reports.

In an interview with Medscape Medical News, Syngal said her ultimate vision of this online tool is that it will be adapted into the electronic medical record (EMR).

"Through the EMR, it might somehow get pushed out to people before an oncology or primary care appointment, or before a mammography or colonoscopy. Then by the time they come in, the doctor or nurse practitioner has the information and can refer them for genetic testing if appropriate," Syngal explained.

The tool is not currently available for routine clinical use. The goal is to make it available online in a couple of months.

Syngal said two versions will be available. One will be a user-friendly version that can be filled out directly by patients and that will tell whether someone passes the threshold of needing genetic testing. The patient would then take that information to their primary care doctor.

With the second version, the doctor and patient would fill out the information together during an office visit.

PREMMplus would be free for the individual patient or provider.

"What we hope is that hospital systems will use it and that insurance companies will also use it as a way to say who needs testing and who to approve for testing," Syngal told Medscape Medical News.

"For a hospital system or a genetic testing company, for example, that wants to integrate it into their direct-to-consumer platform, they would have to take out a license from Dana-Farber, and cost would be negotiated with each entity based on how they're going to use it," Syngal said.

Funding for the research was provided by the National Institutes of Health. A complete list of author disclosures is available with the original article.

J Clin Oncol. Published online August 15, 2022. Abstract

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