NEW YORK – Findings from an ongoing study by National Institutes of Health investigators suggest that nearly half of mothers-to-be who had unusual or indecipherable results from cell-free DNA-based prenatal tests go on to be diagnosed with a previously undetected cancer.
For a paper published in the New England Journal of Medicine on Wednesday, researchers with the National Human Genome Research Institute, the National Cancer Institute, and other branches of the NIH shared findings from a prospective effort known as the "incidental detection of maternal neoplasia through noninvasive cell-free DNA analysis" (IDENTIFY) study that kicked off in 2019.
The work stemmed from the recognition that maternal cancer can be an incidental finding on noninvasive prenatal tests for fetal conditions — a phenomenon that has prompted discussions around consent and return of such secondary results.
The team screened for cancer — using rapid whole-body magnetic resonance imaging (MRI), laboratory testing, and standardized confirmatory cfDNA sequencing done in a research setting — in 107 individuals who had unusual or nonreportable cfDNA sequencing results from testing at a dozen commercial labs in North America during or after pregnancy.
The search uncovered occult cancers in 52 of the 107 women, the researchers reported, noting that the proportion of participants with a cancer diagnosis rose significantly when they focused on cases marked by copy number gains and losses involving several chromosomes in the cfDNA data.
In 47 out of 49 individuals with copy number gains and losses affecting three or more chromosomes, they detected cancer. On the other hand, cfDNA profiles marked by chromosomal gains or losses alone turned up in individuals with nonmalignant conditions such as fibroids.
Nonmalignant explanations ranging from clonal hematopoiesis or placental mosaicism to fibroids or findings related to the fetus were found for 30 of the cases.
While lab testing and physical exams offered only "limited" utility for finding occult cancers, the team saw robust cancer detection capabilities for whole-body MRI screening, which appeared to have a sensitivity of 98 percent, with 88.5 percent specificity.
Findings from the IDENTIFY study were also presented earlier this year at the American College of Medical Genetics and Genomics annual meeting. There, Diana Bianchi, director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and senior author on the new NEJM study, highlighted the importance of investigating nonreportable results from noninvasive prenatal cfDNA testing to find and treat unrecognized maternal cancer as soon as possible.
In a commentary in NEJM, University of North Carolina at Chapel Hill obstetrics and gynecology researcher Neeta Vora argued that the results reveal a need for improved education and guidance around incidental maternal cancer detection for obstetricians and other healthcare providers who may receive cfDNA screening results, along with strategies for helping patients access follow-up testing and care.
"Whole-body MRI is not often ordered by obstetrical providers or covered by insurance," she noted, raising questions about the significant out-of-pocket costs that patients might face when trying to access a whole-body MRI outside of a research setting.
"[W]e still have a long way to go to improve provider education regarding the possibility of identifying maternal cancer through cfDNA screening, as well as to improve laboratory standardization, reporting of suspicious findings, and access to imaging methods such as whole-body MRI," Vora said.
"Until we have addressed these issues," she suggested, "obstetrical providers should consider working in a multidisciplinary team with specialists in oncology, radiology, maternal fetal medicine, and reproductive genetics to develop workflows for pregnant patients who receive cfDNA results that might indicate cancer."