NEW YORK – Following promising pilot study results, Veritas Genetics is planning larger studies of its MyHealthscore polygenic risk score (PRS) assay in breast cancer, as well as a future test expansion into colon cancer.
The small pilot study, which was published recently in the Journal of Personalized Medicine, sought to evaluate how the addition of a PRS to other clinical factors could alter the estimation of an individual's risk for breast cancer, particularly within families with carriers of known pathogenic variants. The study was conducted by researchers affiliated with Veritas Genetics and with the Tor Vergata University Hospital in Rome, Italy.
The retrospective study analyzed four families with histories of breast cancer, in which some family members were carriers of one of the high-risk genes BRCA1 and BRCA2 or the moderate-risk genes PALB2 and ATM.
"We wanted to see if polygenic risk would be useful in refining breast cancer risk and also in understanding how this risk increases with age," said Luís Izquierdo Lopez, chief medical officer of Veritas Genetics and one of the study's authors.
The team calculated PRS using Veritas' CE-IVD MyHealthscore, which evaluates 577,113 breast cancer-associated single-nucleotide polymorphisms (SNPs). The test was developed with the support of Allelica, which provides clinical lab customers with multi-ancestry PRS models along with the software needed to implement them in patient samples.
The researchers first performed a segregation analysis of the pathogenic or likely pathogenic variant found in the family member who had been diagnosed with breast cancer. Then for each unaffected female family member, they evaluated their PRS and determined their lifetime risk of breast cancer. For the probands, the researchers also calculated their lifetime risk of a second breast cancer occurrence.
To determine this lifetime risk, the researchers fed PRS, carrier status, family cancer history, personal clinical data, and certain lifestyle factors into CanRisk, a web interface developed by the University of Cambridge for the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA).
Overall, adding PRS to other clinical factors increased the estimated lifetime breast cancer risk for the probands and any carriers, except for one instance in which the PRS resulted in a slightly lower estimate for the proband, 55.3 percent versus 53.9 percent. By comparison, noncarrier family members had estimated lifetime risks of between approximately 6 percent and 9 percent.
These findings suggested to the researchers that the inclusion of PRS can help healthcare providers more accurately tailor screening and preventive measures for their patients.
But Peter Devilee, professor of cancer genetics at Leiden University in the Netherlands, noted that the study's small size makes it difficult to understand its potential clinical impact at this stage, a critique that Veritas' Izquierdo acknowledged.
Veritas and Tor Vergata are putting together larger follow-on breast cancer studies, Izquierdo noted. These studies will draw on families receiving care at the Tor Vergata hospital. Although this next study will also be retrospective, Izquierdo said that the collaborators intend to later conduct prospective studies to see how cancer risk evolves over time.
Devilee also cautioned that the study provided few details on how its PRS was defined, further complicating drawing any firm conclusions. "It sounds great to have a PRS with over half a million SNPs," he said via email, "but in reality, the effect sizes for most of these SNPs are unknown. This PRS has not been validated in a prospective clinical setting, so it's unclear how well it actually predicts breast cancer."
Giordano Bottà, cofounder and CEO of Allelica, said that the company does know the effect size of each SNP in its models, as this is necessary information for calculating PRS. "We know the effect sizes used in the PRS panel from a GWAS first and then from applying our models to develop the PRS," Bottà said. "Effect size[s] derived from a GWAS are refined and adjusted using our software DISCOVER that implements multiple PRS models."
Although MyHealthscore is currently available only for breast and ovarian cancers, Izquierdo said that the company is interested in expanding it to also cover colon cancer, although a timeline for that effort is not yet available.
The breast and ovarian cancer PRS test requires a physician's prescription, but a spokesperson for Veritas said in an email that the company has its own team of medical geneticists, who can consult with a private consumer and issue their own prescription. "As the test is saliva-based and requires no special preparation other than not eating or drinking for at least a half hour before taking it, it can be done either in a clinical or at-home setting," the spokesperson said.
Veritas Genetics and its subsidiary Veritas Intercontinental were acquired by Irish-American healthcare company LetsGetChecked in 2022, as part of the latter's plan to add whole-genome sequencing to its at-home diagnostics offering.
The acquisition followed a tumultuous period in which Veritas Genetics suspended its US operations and laid off about 30 employees in 2019, citing financial difficulties, then reopened its US office the following year, after securing additional funding.